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Practical blood flow restriction (pBFR), using non-pneumatic elastic cuffs, is a feasible and cost-effective alternative to pneumatic systems. There is evidence that cuff stiffness influences haemodynamic and perceptual responses in the upper body during rest. However, the impact of cuff stiffness during exercise is still unknown. Therefore, this study investigated the influence of cuff stiffness on physiological, perceptual, and performance changes during exercise. In a randomized and counterbalanced order, ten recreationally active males performed four sets of unilateral elbow flexions at 20% of individuals’ one-repetition-maximum with two elastic cuffs of different stiffness (low stiffness cuff [LS] and high stiffness cuff [HS]) each applied with two different overlaps (10% and 20% overlap in relation to the limb circumference) as well as a control condition without pBFR. Before and after exercise, maximal voluntary isometric contraction torque was measured to assess motor performance fatigue. During exercise, muscle oxygen saturation of the biceps brachii as well as effort and exercise-induced muscle pain perception were recorded. Statistical analysis revealed that motor performance fatigue was not different between conditions (BF10 = 0.289). The decline in muscle oxygen saturation (BF10 = 8.508 and BF10 = 1039.543) as well as effort (BF10 = 2646.104 and BF10 = 2.773∙106) and exercise-induced muscle pain perception (BF10 = 14087.983 and BF10 = 7.306∙109) were higher when using the stiffer cuff at 10% and 20% overlap, respectively. Conclusively, physiological and perceptual responses but not motor performance fatigue were affected by cuff stiffness when equal relative overlaps were applied. [ABSTRACT FROM AUTHOR]

[Display omitted] • Abnormal activation of Group I mGluRs induces central sensitization. • Blocking Group Ⅰ mGluRs can alleviate neuropathic pain. • The existing Group I mGluRs orthosteric site antagonists have limitations. • Allosteric Modulators exhibit natural advantages due to allosteric modulation. • Structure based drug discovery may promote drug discovery targeting Group I mGluRs. Neuropathic pain (NP) is a widespread public health problem that existing therapeutic treatments cannot manage adequately; therefore, novel treatment strategies are urgently required. G-protein-coupled receptors are important for intracellular signal transduction, and widely participate in physiological and pathological processes, including pain perception. Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are predominantly implicated in central sensitization, which can lead to hyperalgesia and allodynia. Many orthosteric site antagonists targeting Group I mGluRs have been found to alleviate NP, but their poor efficacy, low selectivity, and numerous side effects limit their development in NP treatment. Here we reviewed the advantages of Group I mGluRs negative allosteric modulators (NAMs) over orthosteric site antagonists based on allosteric modulation mechanism, and the challenges and opportunities of Group I mGluRs NAMs in NP treatment. This article aims to elucidate the advantages and future development potential of Group I mGluRs NAMs in the treatment of NP. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatasia (HPP; OMIM 241510, 241500, and 146300) is a progressive metabolic, genetic disease with wide clinical heterogeneity, ranging from perinatal lethality to mild or moderate localized symptoms. This study aims to analyze the perception of pain, quality of life, and access barriers to healthcare among patients diagnosed with hypophosphatasia in Colombia. In this document we present pain and quality of life results. Methods: This study is an observational cohort of 18 HPP patients registered in the Colombian Association of Patients with Lysosomal Storage Diseases and Other Orphan Diseases (ACOPEL) database. We conducted a descriptive analysis using data from three questionnaires (SF-36, Brief Pain Questionnaire (BPQ), and Hypophosphatasia Impact Patient Survey (HIPS); the latter was translated into Spanish and validated for this study. Results: The most affected features, according to the SF-36 questionnaire, were overall health, vitality, and pain, with a median score above 67%. Patients' perception of their health status (HIPS questionnaire) was favorable, with 38.9% of cases reporting excellent health. On average, results from the BPQ indicated mild to moderate intensity of current pain experienced by patients. Consistency was observed in the reports of either the absence of pain or the presence of mild to moderate intensity when analyzing the results of the three questionnaires. Conclusions: Colombian patients with HPP experience mild to moderate impairment in quality of life and pain that interfere with their daily activities. However, there is wide variability in the results obtained. [ABSTRACT FROM AUTHOR]

Background: Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. Methods: The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. Results: Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. Conclusions: S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD. [ABSTRACT FROM AUTHOR]

Animal care committees remain ambiguous on the need for anesthetics during experimental procedures on invertebrate taxa due to long-standing questioning of their sentience and pain perception. When used, anesthetizing procedures for invertebrates have commonly been adapted from those developed for vertebrates, under the largely unverified assumption that they afford the same benefits. The present study formally tested the efficacy of four common anesthetics of aquatic invertebrates (ethanol, MgCl2, clove oil, MS-222) using behavioural (reaction to physical contact and presence of a predator), physiological (respiration rate), cellular (coelomocytes), and hormonal (cortisol) biomarkers in the holothuroid Cucumaria frondosa (Echinodermata). While subjects recovered from exposures to all anesthetics tested, their responses differed markedly. Ethanol did not immobilize the individuals and concurrently increased their respiration rate, and cellular and hormonal stress markers. MgCl2 and clove oil reduced the behavioural and physiological responses, and decreased the cellular markers, but increased the cortisol levels. Only MS-222 fully immobilized the treated individuals and decreased their respiration rate, both during exposure and throughout ulterior interactions with a predator, while keeping coelomocyte counts and cortisol concentrations at baseline levels. MS-222 thus appears to induce the loss of sensation, representing a promising anesthetic and sedative in soft-bodied aquatic invertebrates. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are there neurobiological changes induced by endometriosis? SUMMARY ANSWER Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis. WHAT IS KNOWN ALREADY Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied by comorbid mental disorders. Only one study with a number of limitations has investigated changes in gray matter volumes and functional connectivity in a small group of patients with endometriosis. STUDY DESIGN, SIZE, DURATION This prospective study recruited 53 women undergoing a laparoscopy due to suspicion of symptomatic endometriosis and 25 healthy, pain-free women. Clinical and psychological characteristics, thermal pain perception, and voxel- and surface-based morphology were assessed in all study participants. Thereafter, the patients underwent a laparoscopy, where endometriosis was either histologically confirmed and removed, or ruled out. Correspondingly, patients were assigned into the group with endometriosis (n = 27) or with endometriosis-independent CPP (n = 26) and compared to the pain-free controls. PARTICIPANTS/MATERIALS, SETTING, METHODS The study groups were generally representative for the population of women with endometriosis. Sociodemographic, medical, clinical, and psychological characteristics were collected using various questionnaires and a structured clinical interview. Thermal pain perception and voxel- and surface-based morphometry were assessed using thermode and MRI, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Despite comparable pain intensity and burden of mental disorders, both patient groups demonstrated distinct neurobiological patterns. Women with endometriosis exhibited increased gray matter volume (GMV) in the left cerebellum, lingual gyrus and calcarine gyrus, compared to those with endometriosis-independent CPP. Patients with CPP had decreased GMV in the right cerebellum as compared to controls. Dysmenorrhoea severity correlated positively with GMV in the left inferior parietal lobule, whereas depressive symptoms were associated with decreased GMV in the right superior medial gyrus across patient groups. Dyspareunia correlated negatively with cortical thickness in the left inferior temporal gyrus and left middle temporal gyrus. LIMITATIONS, REASONS FOR CAUTION The study groups differed in a few baseline-characteristics, including educational levels, smoking and BMI. While measuring pain perception thresholds, we did not attempt to mimic CPP by placement of the thermode on the abdominal wall. WIDER IMPLICATIONS OF THE FINDINGS Changes in gray matter volume associated with endometriosis differ from those observed in women with endometriosis-independent CPP. Our results underline an involvement of the cerebellum in pain perception and the pathogenesis of pain associated with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the START Program of the Faculty of Medicine, RWTH Aachen, Germany, and supported by the International Research Training Group (IRTG 2150) of the German Research Foundation (DFG)—269953372/GRK2150, Germany. S.T. was supported by postdoctoral fellowship of the Faculty of Medicine, RWTH Aachen, Germany. There are no conflicts of interest. TRIAL REGISTRATION NUMBER DRKS00021236 [ABSTRACT FROM AUTHOR]

Background: Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution. Objective: To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain‐free controls (CON) using structural and diffusion MRI. Methods: A case–control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1‐weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity. Results: Patients with FM had smaller volume in the right thalamus than patients with TMD (p =.020) and CON (p =.030). The right thalamus volume was negatively correlated to pain intensity (r = −0.37, p =.022) and pain‐related disability (r = −0.45, p =.004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p =.005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = − 0.48, p =.002). Conclusions: This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system. [ABSTRACT FROM AUTHOR]

Background: Sweet taste administration before dental injections helps to control associated pain in children. Aim: To evaluate the efficacy of using a sugar‐free flavor on pain perception during dental injections. Design: Children (n = 84) aged 4–9 (mean 6.71 ± 1.55) years who required buccal infiltration bilaterally participated in this split‐mouth randomized crossover study. On the test side (flavor visit), infiltration injections were applied after receiving a sugar‐free flavor. On the control side (no flavor visit), sterile water was administered. Demographic characteristics, body mass index (BMI), and sweet taste preference (STP) were recorded. Pain perception during injection was measured using heart rate (HR), sound, eyes, and motor (SEM) scale, and Wong–Baker Faces pain scale (WBFPS). Results: Most children had healthy weight (72.6%) and equal STP (32.1%). In the test side, mean HR during injection, HR differences before and during injection, and SEM scores were significantly lower (p <.001, for all). There was no significant difference in the WBFPS between both visits. Flavor had a significant effect on pain reduction (p =.001 for HR, p =.000 for SEM), whereas age, gender, BMI, STP, and treatment side did not. Treatment sequence had a significant effect on total SEM scores (p =.021); children who received the flavor during their first visit had lower SEM scores. Conclusion: Using a sugar‐free flavor before dental injections helps in reducing associated pain in children. [ABSTRACT FROM AUTHOR]

Pain perception is influenced not only by sensory input from afferent neurons but also by cognitive factors such as prior expectations. It has been suggested that overly precise priors may be a key contributing factor to chronic pain states such as neuropathic pain. However, it remains an open question how overly precise priors in favor of pain might arise. Here, we first verify that a Bayesian approach can describe how statistical integration of prior expectations and sensory input results in pain phenomena such as placebo hypoalgesia, nocebo hyperalgesia, chronic pain, and spontaneous neuropathic pain. Our results indicate that the value of the prior, which is determined by the internal model parameters, may be a key contributor to these phenomena. Next, we apply a hierarchical Bayesian approach to update the parameters of the internal model based on the difference between the predicted and the perceived pain, to reflect that people integrate prior experiences in their future expectations. In contrast with simpler approaches, this hierarchical model structure is able to show for placebo hypoalgesia and nocebo hyperalgesia how these phenomena can arise from prior experiences in the form of a classical conditioning procedure. We also demonstrate the phenomenon of offset analgesia, in which a disproportionally large pain decrease is obtained following a minor reduction in noxious stimulus intensity. Finally, we turn to simulations of neuropathic pain, where our hierarchical model corroborates that persistent non-neuropathic pain is a risk factor for developing neuropathic pain following denervation, and additionally offers an interesting prediction that complete absence of informative painful experiences could be a similar risk factor. Taken together, these results provide insight to how prior experiences may contribute to pain perception, in both experimental and neuropathic pain, which in turn might be informative for improving strategies of pain prevention and relief. Author summary: To efficiently navigate the world and avoid harmful situations, it is beneficial to learn from prior pain experiences. This learning process typically results in certain contexts being associated with an expected level of pain, which subsequently influences pain perception. While this process of pain anticipation has evolved as a mechanism for avoiding harm, recent research indicates overly precise expectations of pain may in fact contribute to certain chronic pain conditions, in which pain persists even after tissue damage has healed, or even arises without any initiating injury. However, it remains an open question how prior experiences contribute to such overly precise expectations of pain. Here, we mathematically model the pain-learning-process. Our model successfully describes several counterintuitive but well-documented pain phenomena. We also make predictions of how prior experiences may contribute the perception of pain and how the same learning process could be leveraged to improve strategies of pain prevention and relief. [ABSTRACT FROM AUTHOR]

With the National Institutes of Health's mandate to consider sex as a biological variable (SABV), there has been a significant increase of studies utilizing both sexes. Historically, we have known that biological sex and hormones influence immunological processes and now studies focusing on interactions between the immune, endocrine, and nervous systems are revealing sex differences that influence pain behavior and various molecular and biochemical processes. Neuroendocrine-immune interactions represent a key integrative discipline that will reveal critical processes in each field as it pertains to novel mechanisms in sex differences and necessary therapeutics. Here we appraise preclinical and clinical literature to discuss these interactions and key pathways that drive cell- and sex-specific differences in immunity, pain, and physiology. Plain English summary: In the last decade, NIH-funded basic and clinical research studies have been mandated to include sex as a biological variable, and this has resulted in a boom of studies discovering sex differences. We know that females are more likely than males to develop chronic pain conditions and experience higher levels of pain for longer periods of time. Conditions that demonstrate this include migraine, arthritis, and peripheral neuropathy. Furthermore, these sex differences extend to surgical outcomes and are observable at the molecular, cellular, and systemic levels. Although pain perception pathways differ by sex, studies are also focusing on differences in the "conversation" between the immune system and the nervous system while addressing implications of sex hormones to gain a better understanding of the impact on pain, physiology, and behavior. Lifestyle factors such as diet and alcohol consumption also play a role in affecting the perception and impact of pain conditions. As this area of research continues to grow, the development and availability of sex-specific treatment options will grow and lead to improved patient outcomes and more effective pain management strategies. Highlights: Immune cell types and molecular pathways drive sex specific differences in inflammatory and neuropathic pain. TLR4 involvement in pain pathways show contextual sex-specific variations and its interaction with TRPV1 channels adds complexity to nociceptor physiology. Female mice tend to exhibit stronger TRPV1-mediated pain responses compared to males due to estrogen enhancement of TRPV1 expression levels. The interplay between nuclear receptors (PPARγ, PPARα) and prolactin receptors influences sex-specific neuroimmune interactions. In males, PPARα impacts immune responses and neuroinflammation. In females, PPARγ activity influences pain perception and PRL influences pain sensitivity. Personalized approaches are needed for pain management in males and females due to sex differences in pain perception and treatment outcomes driven by variations in hormone levels, adiposity, and neuroimmune mechanisms of inflammation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present investigation was to evaluate the possible anxiolytic effect of jasmine aromatherapy in pediatric dental procedures. Materials and Methods: A parallel randomized single-blinded placebo-controlled clinical trial was designed and conducted from February 19 until April 19, 2020, on children aged 7 to 12 years-old requiring class 1 restorative treatment of primary or permanent tooth with infiltration anesthesia. Interventions were defined as 15 minutes of aromatherapy using 2mL of jasmine extract for the intervention group, and with water for the control group. Outcomes were defined as child's anxiety and pain perception, measured by modified child dental anxiety scale (MCDAS), visual analogue scale (VAS) and changes of vital signs. After the patients received interventions based on their groups, their data was collected and analyzed. We used parametric tests and linear regression for outcome comparisons. Results: 56 patients were randomized and allocated in two groups, 28 to each. The groups did not differ significantly regarding age, sex, heart rate and O2 saturation before, during, and after procedures. Based on multivariable regression, the intervention group showed a significantly reduced MCDAS (B (95% CI) =-2.11 (-4.09, -0.13), P=0.04) and VAS (B (95% CI) =-2.30 (-3.50, -1.10), P<0.001) scores. Conclusion: Jasmine aromatherapy showed to be effective in reducing children's anxiety and pain perception during dental procedures and therefore, can be suggested as a cheap and practical complementary method in dental practice. [ABSTRACT FROM AUTHOR]

Neuronal ensemble activity entrained by local field potential (LFP) patterns underlies a variety of brain functions, including emotion, cognition, and pain perception. Recent advances in machine learning approaches may enable more effective methods for analyzing LFP patterns across multiple brain areas than conventional time-frequency analysis. In this study, we tested the performance of two machine learning algorithms, AlexNet and the Transformer models, to classify LFP patterns in eight pain-related brain regions before and during acetic acid-induced visceral pain behaviors. Over short time windows lasting several seconds, applying AlexNet to LFP power datasets, but not to raw time-series LFP traces from multiple brain areas, successfully achieved superior classification performance compared with simple LFP power analysis. Furthermore, applying the Transformer directly to the raw LFP traces achieved significantly superior classification performance than AlexNet when using LFP power datasets. These results demonstrate the utility of the Transformer in the analysis of neurophysiological signals, and pave the way for its future applications in the decoding of more complex neuronal activity patterns. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterial and MethodsResultsConclusion\nIMPLICATIONS FOR REHABILITATIONPhantom limb pain (PLP) is a condition that greatly diminishes quality of life. Phantom motor execution (PME), enabled by myoelectric pattern recognition combined with virtual and augmented reality, is a novel treatment for PLP. Here we, aimed to describe patients’ experiences of this treatment.Qualitative, using semi-structured interviews one month after completed PME treatment. Twenty-one Swedish and Dutch patients (mean age 57, 16 males, 16 lower limb amputations) participated. The analysis followed the framework approach.The main themes were 1) treatment effects on the perception of the phantom limb, 2) living with PLP before and after treatment, and 3) facilitators and barriers to treatment. Most participants learned to control their phantom limb, perceived it more positively and as more complete. This control over the phantom limb became a tool for managing PLP. Most participants’ outlook on life and energy levels improved after treatment. Being mentally focused during treatment was important. Therapists were pivotal to the success of the treatment.Controlling the phantom limb improved their perception of it and pain management, self-agency, and quality of life. The therapists’ role was invaluable. We suggest training for patients in phantom limb control before and after amputation.Phantom limb pain is a common and chronic problem after amputation. When informing patients about the phantom limb phenomenon it is important to use positive wording and to acknowledge its existence as normal.Controlling the phantom limb is a key for the success of the phantom motor execution (PME) treatment and should therefore receive clinicians’ attention from the early stages after surgery and onwards.The role of the therapist is invaluable in teaching, supporting and coaching patients receiving PME treatment.In order to facilitate successful outcome of the PME treatment it is important to consider and reduce potential barriers to patient adherence to the treatment.Phantom limb pain is a common and chronic problem after amputation. When informing patients about the phantom limb phenomenon it is important to use positive wording and to acknowledge its existence as normal.Controlling the phantom limb is a key for the success of the phantom motor execution (PME) treatment and should therefore receive clinicians’ attention from the early stages after surgery and onwards.The role of the therapist is invaluable in teaching, supporting and coaching patients receiving PME treatment.In order to facilitate successful outcome of the PME treatment it is important to consider and reduce potential barriers to patient adherence to the treatment. [ABSTRACT FROM AUTHOR]

Key points The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by ‘top‐down’ processes occurring in the brain, brainstem and spinal cord, known as ‘descending modulation’. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low‐frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial ‘baroreceptor stimulation’ in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no‐pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no‐pain. Baroreceptor activation decreases pain in participants with no‐pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no‐pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate pain perception and analgesic use between patients who underwent endometriosis-specific laparoscopic surgery compared to laparoscopic hysterectomy. Material and methods: This retrospective cohort study included women diagnosed with endometriosis who underwent laparoscopic surgery from 1/2019 to 11/2022. The control group consisted of premenopausal women who underwent laparoscopic hysterectomy, which was considered a similarly extensive surgery. Demographics, preoperative and post-operative data were compared between groups. Post-operative pain scores on a visual analogue scale (VAS) between 0 (no pain) and 10 (worst pain) were compared between groups for each post-operative day (POD). Standard pain relief analgesia on POD 0–1 included fixed intravenous treatment with paracetamol and intramuscular diclofenac. The need for additional analgesics (morphine or dipyrone) beyond the standard pain relief protocol was compared between groups. Results: Among 200 patients who underwent laparoscopic surgery, 100 (50%) were in the endometriosis group and 100 (50%) in the hysterectomy group. The endometriosis group was characterized by younger age and lower parity (both, p<0.001). There was no significant difference between the groups in mean VAS scores for each post-operative day. However, among patients who needed additional analgesics beyond the standard protocol on POD 1, a higher percentage of women in the endometriosis group used opioids rather than milder analgesics, as compared to controls (1% vs. 0.2%, respectively, p = 0.03). Conclusion: Increased post-operative morphine use was observed in patients with endometriosis following laparoscopic surgery, despite no significant difference in mean VAS scores during the post-operative days. These findings suggest that personalized pain relief protocols should be adjusted for women with endometriosis. [ABSTRACT FROM AUTHOR]

Introduction: Surgery and anaesthesia are uncomfortable experiences for patients, often causing stress and anxiety that can impede the intended therapeutic outcomes. Increased stress and anxiety may have a deleterious impact on post-operative analgesic use and pain perception. Advancements in anaesthesia extend anesthesiologists’ role beyond the surgery, allowing for an anaesthesia in diverse procedures, and raising patient expectations for comfortable treatment. (1) At least two days before the operation, anxiety affects a majority of patients scheduled for surgery. Materials And Methods: After obtaining institutional ethics committee approval (SGRD/IEC/2022-163 dated 13.12.2022) and the patient’s informed consent, this prospective semi-experimental randomised single-blind controlled study was conducted to investigate the effect of music (the independent variable) on cortisol levels, VAS-A scores and VAS pain scores (the dependent variables). The study was conducted in 100 patients of either sex in the age group between 18 to 60, with ASA classification I and II, undergoing Laparoscopic Cholecystectomy from January 2023 to December 2023.Results: The demographic characteristics of the study participants were analysed and there were no statistically significant differences in the mean values of all the characteristics. (Table 1) As shown in Table 2 on comparing mean VAS-A scores among the three groups, the difference at the baseline was statistically not significant (p-value 0.77) but when the three groups were compared after the respective interventions, the scores before surgery were significantly lower in group A than in groups B and C (p-value 0.037) additionally, scores of group B were significantly lower than group C. Similar findings were seen when the three groups were compared after surgery (p-value 0.02).Conclusion: Music therapy especially listening to music of choice is a safe and effective non-invasive non-pharmacological intervention with several benefits for surgical patients. It reduces the need for pain medication during the postoperative period without causing any side effects. It also hinders the increase of blood cortisol levels. Additionally, music therapy helps lower anxiety enhancing the overall surgical experience for patients. [ABSTRACT FROM AUTHOR]

We conducted a systematic review investigating the influence of visual perspective and body ownership (BO) on vicarious brain resonance and vicarious sensations during the observation of pain and touch. Indeed, the way in which brain reactivity and the phenomenological experience can be modulated by blurring the bodily boundaries of self-other distinction is still unclear. We screened Scopus and WebOfScience, and identified 31 articles, published from 2000 to 2022. Results show that assuming an egocentric perspective enhances vicarious resonance and vicarious sensations. Studies on synaesthetes suggest that vicarious conscious experiences are associated with an increased tendency to embody fake body parts, even in the absence of congruent multisensory stimulation. Moreover, immersive virtual reality studies show that the type of embodied virtual body can affect high-order sensations such as appropriateness, unpleasantness, and erogeneity, associated with the touched body part and the toucher's social identity. We conclude that perspective plays a key role in the resonance with others' pain and touch, and full-BO over virtual avatars allows investigation of complex aspects of pain and touch perception which would not be possible in reality. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Urodynamics (UDS) assesses voiding dysfunction using intravesical, vaginal, or rectal catheters, which can be distressing. This study was aimed at utilizing mindfulness to reduce anxiety and pain in patients undergoing UDS. Methods: A single-institution randomized controlled trial was conducted on 60 patients who underwent UDS. Patients were assigned to a mindfulness group (n = 30) or a control group (n = 30). Before UDS testing, all patients completed validated questionnaires assessing lower urinary tract symptoms (Urogenital Distress Inventory 6, UDI-6), anxiety (State-Trait Anxiety Inventory 6, STAI-6), and pain (Visual Analog Scale, VAS). The mindfulness group listened to a mindfulness audio prompt before UDS. All patients received standardized UDS education before UDS testing in a calm environment. After UDS testing, all patients completed validated UDS-perception questionnaires, STAI-6, Likert scale, and VAS surveys. Statistical analysis was performed using paired t tests, independent t tests, Wilcoxon, and Chi-squared tests. Results: Both groups had similar demographics, history of prior UDS, anxiety, and baseline UDI-6 and STAI-6. Post-UDS, anxiety scores decreased in both groups, with the mindfulness group reporting significant improvement in "calmness" (mean 1.7, SD = 0.84) compared with the control group (mean 2.3, SD = 1.0, p < 0.05). The mindfulness group reported increased relaxation whereas the control group reported decreased relaxation post-UDS. Patients in both groups without a history of UDS had a significant improvement in total anxiety compared with those with a history of UDS. Conclusion: Mindfulness meditation may improve calmness and relaxation for patients undergoing UDS. [ABSTRACT FROM AUTHOR]

Background: Multiple factors, including neurobiological, hormonal, psychological, and social/cultural norms, influence the manner in which individuals experience pain. Adipose tissue, once considered solely an energy storage site, has been recognized as a significant endocrine organ that produces and releases a range of hormones and cytokines. In recent years, research has highlighted the role of adipose tissue and its endocrine factors in the pathophysiology of pain. Summary: This narrative review aimed to provide a comprehensive overview of the current knowledge on the endocrine aspects of pain pathophysiology, with a specific focus on adipose tissue. We examine the role of adipokines released by adipose tissue, such as leptin, adiponectin, resistin, visfatin, asprosin in pain perception and response. We also explore the clinical implications of these findings, including the potential for personalized pain management based on endocrine factors and adipose tissue. Key Messages: Overall, given this background, this review intended to highlight the importance of understanding the endocrine aspects of pain pathophysiology, particularly focusing on the role of adipose tissue, in the development of chronic pain and adipokines. Better understanding the role of adipokines in pain modulation might have therapeutic implications by providing novel targets for addressing underlying mechanism rather than directly focusing on symptoms for chronic pain, particularly in obese individuals. [ABSTRACT FROM AUTHOR]

Objective: The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB1), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing. Methods: We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning. Results: TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses. Conclusion: TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning. [ABSTRACT FROM AUTHOR]

Background: Dermatosurgery is one of the fastest expanding subspecialty of dermatology. Local anesthetic agents play an important role in these procedures. Materials and Methods: This was a prospective, interventional study that included eighty patients with forty patients in each group (groups A and B). Group A: Topical 2.5% lignocaine and 2.5% prilocaine cream. Group B: Infiltration of 2% lignocaine Injection. Patients satisfying the inclusion criteria were recruited for the study. The patients were asked to rate pain perception at the time of drug administration and, then, during and after the surgical procedure using a visual, analogue scale separately. Results: In our study, the most common age group at presentation was 21-40 years. Males constituted 57.8%, whereas females constituted 42.2%. The common procedures performed in our study were electrocautery 33.3%, intralesional steroid 18.9%, and intralesional PRP 15.7%. In the topical EMLA cream group, the VAS score during drug administration was 0. In the lignocaine infiltration group, 70% were found to have VAS a score of 4-6, and 30% had a VAS score of 1-3, preprocedurally. The mean VAS score during the procedure was 3.36 for the topical EMLA cream group and 1.33 for the lignocaine infiltration group. The post-procedural VAS score showed similar results as the procedural VAS score. Conclusion: The results of our study showed that topical EMLA cream is a better choice of anesthesia in superficial aesthetic and dermatosurgical procedures in providing adequate analgesia. [ABSTRACT FROM AUTHOR]

Background: Chronic widespread pain (CWP) affects approximately 10% of the adult population globally, causing significant physical and psychological distress. Micronutrients, such as iron, copper, zinc, and magnesium, are essential in various physiological functions, and their imbalances may impact pain perception and chronic pain conditions. Methods: This study used Mendelian randomization (MR) to investigate the causal relationships between micronutrient levels and CWP. Data were obtained from genome-wide association studies (GWASs) for iron, copper, zinc, and magnesium, and CWP data were sourced from large-scale GWASs with 461,857 European participants. Genetic variants were used as instrumental variables to infer causal relationships, minimizing confounding factors. Results: MR analysis revealed a significant association between higher iron levels and an increased risk of CWP (IVW, OR 1.01, 95% CI: 1.00–1.01, p = 0.029). This finding was supported by the weighted median and MR-Egger methods. No significant associations were found for copper, zinc, and magnesium levels. Conclusions: These results suggest that iron levels may influence pain perception and chronic pain conditions. Balanced iron levels are crucial for managing chronic pain. Regular monitoring and personalized treatment plans could benefit individuals with CWP. Further research is needed to understand the mechanisms linking micronutrient levels to chronic pain and to develop targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: The perception of effort exerts influence in determining task failure during endurance performance. Training interventions blending physical and cognitive tasks yielded promising results in enhancing performance. Motor imagery can decrease the perception of effort. Whether combining motor imagery and physical training improves endurance remains to be understood, and this was the aim of this study. Methods: Participants (24 ± 3 year) were assigned to a motor imagery (n = 16) or a control (n = 17) group. Both groups engaged in physical exercises targeting the knee extensors (i.e., wall squat, 12 training sessions, 14-days), with participants from the motor imagery group also performing motor imagery. Each participant visited the laboratory Pre and Post-training, during which we assessed endurance performance through a sustained submaximal isometric knee extension contraction until task failure, at either 20% or 40% of the maximal voluntary contraction peak torque. Perceptions of effort and muscle pain were measured during the exercise. Results: We reported no changes in endurance performance for the control group. Endurance performance in the motor imagery group exhibited significant improvements when the intensity of the sustained isometric exercise closely matched that used in training. These enhancements were less pronounced when considering the higher exercise intensity. No reduction in perception of effort was observed in both groups. There was a noticeable decrease in muscle pain perception within the motor imagery group Post training. Conclusion: Combining motor imagery and physical training may offer a promising avenue for enhancing endurance performance and managing pain in various contexts. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) affect approximately half of all children worldwide. These experiences have been linked to increased pain sensitivity in adulthood and a higher likelihood of developing severe chronic pain. However, most studies have assessed the effects of ACEs retrospectively, long after they occurred, leaving room for other factors to influence the observed outcomes. We investigated, for the first time, the association between ACEs and concurrent pain perception among young children who live in a conflict zone and are consistently exposed to potentially traumatic experiences. Participants were 60 elementary school children (ages 8-11 years) living in conflict regions (n = 39) or nonconflict regions (n = 21). Posttraumatic stress symptom (PTSS) severity, traumatic exposure, pressure pain threshold (PPT), and mechanical detection threshold (MDT) were measured. Traumaexposed children had significantly lower PPT than did controls, but MDT was similar across groups. Pressure pain threshold correlated positively with proximity to the conflict zone and inversely with traumatic exposure magnitude and PTSS severity. In addition, PTSSs moderated the relationship between repeated traumatic exposure and PPT. Children with higher PTSS severity displayed pain hypersensitivity regardless of their traumatic exposure level, whereas in children with lower PTSS severity, greater traumatic exposure correlated with pain hypersensitivity. The results suggest that ACEs among children lead to concurrent pain hypersensitivity and distress and may put them at elevated risk of chronic pain early in life. In addition, our findings emphasize the need for identifying children with various PTSS levels to provide tailored interventions and mitigate the long-term negative effects of ACEs. [ABSTRACT FROM AUTHOR]

Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signaled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants' pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is, when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease. [ABSTRACT FROM AUTHOR]

Introduction: Pain is the most common complaint among cancer patients, significantly impairing their health-related quality of life (HRQOL). There is limited evidence on the characteristics of pain among cancer patients in Nepal with low-resource settings. Objectives: The primary objective of this study was to evaluate the clinical characteristics of pain, factors influencing pain intensity, and the association of pain severity with quality of life (QoL) among cancer patients. Secondary objectives included investigating perceived barriers to pain management and medication adherence among these patients. Methods: This multi-center, cross-sectional study enrolled adult patients (over 18 years old) with reported cancer diagnoses experiencing pain. Socio-demographic characteristics (e.g., age, gender, educational status), clinical characteristics (e.g. cancer diagnosis, staging), and pain characteristics (e.g., duration, type, location, medicines used for pain management, etc.) were recorded. Outcomes were assessed using the Numeric rating scale (NRS), Pain management Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, Barriers Questionnaire II, Medication Adherence Rating Scale, and Hospital Anxiety and Depression Scale. Results: Four hundred and eight patients participated in the study. The mean ± SD age was 54.87 ± 15.65, with 226 patients (55.4%) being female. The most common cancer diagnoses were cervical (17.6%), lung (11.8%), and colon/rectum (12.0%) cancers. The most common pain locations were the head and neck (27.0%); a majority (55.6%) reported pain duration of more than 3 months. Nociceptive pain was reported by 42.4% of patients; the mean ± SD of NRS was 4.31 ± 2.69, with 32.4% of patients experiencing moderate pain. Patients with mixed pain type (B = 1.458, p < 0.001) or pain in multiple sites (B = 1.175, p < 0.001), lower Karnofsky Performance Status (KPS) (B = -1.308, p < 0.001), and specific cancer diagnoses such as prostate (B = -2.045, p = 0.002), pancreatic (B = 1.852, p = 0.004), oesophageal (B = 1.674, p = 0.012), and ovarian cancer (B = 1.967, p = 0.047), experienced varying degrees of increased NRS score. The combined chemotherapy and radiotherapy treatment modality was associated with a lower NRS score (B = -0.583, p = 0.017). A significant inverse relationship was observed between pain severity and global health status/QoL (B = -37.36, p < 0.001. Key barriers to pain management included moderate perceptions of physiological effects, communication issues between doctors and patients, and concerns about the harmful effects of pain medicine. The prevalence of non-adherence to pain medications was 13.97%. Conclusion: In conclusion, this study highlights the multi-faceted nature of pain management and QoL for cancer patients in Nepal with low-resource settings. These findings underscore the multifactorial nature of pain perception in cancer patients, with mixed pain types, pain in multiple sites, lower KPS, and specific cancer diagnoses, all contributing significantly to pain severity. Additionally, pain severity was associated with declining QoL. These findings contribute valuable insights into the complex aspects of cancer pain and its broader implications for the well-being of patients, offering a foundation for targeted interventions and improved pain management strategies in the context of cancer care in low-resource settings. [ABSTRACT FROM AUTHOR]

Background The veterinary workplace carries a high risk of staff accidents and injuries, yet there is scant research exploring it in comparison with other comparable fields, such as human medicine. Aims To understand how veterinary professionals define injuries and to understand what injuries they do, or do not, deem reportable. Methods A cross-sectional survey comprising demographic questions and open-text questions was shared with veterinary practice staff across the UK. Data were analysed descriptively and using an inductive content analysis. Results There were 740 respondents, who were broadly representative of the veterinary profession. There were differences in how injuries were defined; for example, small animal veterinarians expected injuries to involve blood, while equine and production animal veterinarians were more likely to expect injuries to reduce their ability to perform work and require medical treatment. Many suggested that 'all' workplace injuries should be reported; however, 'minor' injuries were often overlooked, for example, needlestick injuries did not always meet the criteria of being an 'injury'. Injuries caused by staff themselves (e.g. trips) were less likely to be reported than injuries that could be blamed on an external factor (e.g. dog bite). Conclusions Collectively, the data suggest a wide-ranging perception of risk of injury in practice, with some harms seen as 'everyday norms'. Veterinary practices should interpret their injury statistics with a high degree of caution. They should explore the microcultures within their practices relating to worker perception of risk, injury and barriers to reporting. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of Eutectic Mixture of Local Anesthetic (EMLA), a topical anesthetic cream, in office-based invasive andrological procedures such as hydrocelectomy, spermatocelectomy, and others, aimed at minimizing pain perception and enhancing the overall patient experience. A double-blinded randomized controlled trial was conducted for patients undergoing scrotal andrology surgeries under LA. Power calculation was performed with an estimated sample size of 72. Participants were randomly assigned in a 1:1 ratio to topical EMLA + LA versus LA alone. In the post-operative recovery area, patient will be asked to complete a VAS questionnaire rating pain with LA administration and pain with procedure. Analysis comparing VAS pain scores of both groups was performed using the independent sample t-test method. Seventy-two patients were included in our analysis, with 36 in the control and 36 in the intervention arm. For patient pain with administration of LA, the control arm reported an average VAS pain score of 4.31, compared to 3.72 in the intervention arm (P =.319). For patient pain with procedure, patients in the control arm reported a median VAS pain score of 3.47 compared to 3.03 (P =.432) in the intervention arm. Overall, 86% (62/72) of patients reported that they would either be "very likely" (4/5) or "highly likely" (5/5) to undergo future procedures under local anesthetic. While performing scrotal surgeries under LA appears to be well tolerated and a feasible option, the application of EMLA cream does not appear to significantly alter patient-reported outcomes. [ABSTRACT FROM AUTHOR]

• Tonic painful stimulation entailed a decrease in EEG alpha power, together with cardiac, electrodermal and pupil activation. • Taking in isolation, none of these activities was specific to pain. • Powerful discrimination between painful and non-painful conditions was achieved only when EEG and autonomic changes were combined. To assess the value of combining brain and autonomic measures to discriminate the subjective perception of pain from other sensory-cognitive activations. 20 healthy individuals received 2 types of tonic painful stimulation delivered to the hand: electrical stimuli and immersion in 10 Celsius degree (°C) water, which were contrasted with non-painful immersion in 15 °C water, and stressful cognitive testing. High-density electroencephalography (EEG) and autonomic measures (pupillary, electrodermal and cardiovascular) were continuously recorded, and the accuracy of pain detection based on combinations of electrophysiological features was assessed using machine learning procedures. Painful stimuli induced a significant decrease in contralateral EEG alpha power. Cardiac, electrodermal and pupillary reactivities occurred in both painful and stressful conditions. Classification models, trained on leave-one-out cross-validation folds, showed low accuracy (61–73%) of cortical and autonomic features taken independently, while their combination significantly improved accuracy to 93% in individual reports. Changes in cortical oscillations reflecting somatosensory salience and autonomic changes reflecting arousal can be triggered by many activating signals other than pain; conversely, the simultaneous occurrence of somatosensory activation plus strong autonomic arousal has great probability of reflecting pain uniquely. Combining changes in cortical and autonomic reactivities appears critical to derive accurate indexes of acute pain perception. [ABSTRACT FROM AUTHOR]

Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on μ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin–angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a public health issue, leading to substantial healthcare costs and diminished quality of life for sufferers. While the role of anxiety in pain modulation has been extensively studied, the effects of other emotional states on the body's pain control mechanisms remain less understood. This study sought to explore how different emotions (happiness, anger, sadness, and interest) affect conditioned pain modulation (CPM) and the wind-up phenomenon in healthy adults. Methods: This randomized controlled, cross-over trial involved 28 healthy participants aged 18–60. Participants watched video clips designed to induce specific emotions: happiness, anger, sadness, and interest. Emotional states were assessed using a 7-point Likert scale. Pain modulation was measured using CPM and the wind-up phenomenon. CPM was assessed with a hot water bath as the conditioning stimulus and pressure pain tolerance as the test stimulus. Wind-up was measured using pinprick needle stimulators and a visual analog scale. Data were analyzed using paired t tests to compare pre- and post-emotion induction values. Results: Significant changes in emotional self-assessment values were observed for all emotions. Happiness increased CPM (4.6 ± 11.4, p = 0.04277), while sadness − 9.9 ± 23.1, p = 0.03211) and anger − 9.1 ± 23.3, p = 0.04804) decreased it. Interest did not significantly alter CPM (− 5.1 ± 25.8, p = 0.31042). No significant effects were found for the wind-up phenomenon across any emotional states. Conclusion: This study shows that emotional states significantly affect the body's ability to modulate pain. Positive emotions like happiness enhance pain inhibition, while negative emotions such as sadness and anger impair it. These findings suggest that emotional modulation techniques could be integrated into pain management strategies to improve patient outcomes. Further research should explore a broader range of emotions and include objective measures to validate these results. Plain Language Summary: Chronic pain is a widespread problem that affects millions of people and leads to high healthcare costs and decreased quality of life. Understanding how emotions impact pain can help us find better ways to manage it. This study looked at how different emotions (happiness, anger, sadness, and interest) affect the ability of the body to naturally control pain in healthy adults. Participants experienced different tests in a random order, like flipping a coin to decide the order. Each participant took part in all the tests to compare how different conditions affected them. We measured changes in their pain perception using two methods: conditioned pain modulation, which reflects how well the body can suppress pain after experiencing another painful stimulus, and the wind-up phenomenon, which measures how pain intensity increases with repeated stimulation. We found that emotions affected the body's ability to control pain. Sadness and anger reduced the efficacy of conditioned pain modulation, making it harder for the body to reduce pain. Happiness improved CPM, enhancing the body's natural ability to stop pain. Interest did not significantly change how pain was felt. We also did not find any significant changes in the wind-up phenomenon for any of the emotions tested. The results suggest that positive emotions like happiness can help reduce pain, while negative emotions like sadness and anger can make pain worse. This could lead to new pain management approaches that include methods to boost positive emotions and reduce negative ones. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate the effectiveness of intensive short-term dynamic psychotherapy on pain perception and pain catastrophizing in women with breast cancer. Methods: In this quasi-experimental study, 30 women with breast cancer who referred to Imam Khomeini Hospital in Sari in 2024 were studied using convenience sampling. They were then randomly assigned to two groups: the short-term intensive psychodynamic intervention group (15 participants) and the control group (15 participants) without any intervention. The short-term intensive psychodynamic intervention was implemented according to the protocol by Teska et al. (2005) over 16 weekly sessions, each lasting one and a half hours. The samples were assessed at two stages, pre-test and post-test, using the Pain Perception Questionnaire by Schaal et al. (2010) and the Pain Catastrophizing Scale by Rahmati et al. (2017). Data were analyzed using repeated measures multivariate analysis of variance in SPSS24 software. Findings: In the intervention group, the mean scores for pain catastrophizing were (17.20±36.60) and for pain perception were (36.33±80.80) in the pre-test and post-test stages, respectively. Post-test scores significantly decreased compared to pre-test scores in the components of pain catastrophizing and pain perception in the experimental group compared to the control group. Additionally, the results showed that intensive short-term dynamic psychotherapy had a statistically significant effect on pain catastrophizing (P<0.05, F=24.41) and pain perception (P<0.05, F=56.201) after adjusting the means of the two groups based on the pre-test score. Conclusion: The results indicate the effectiveness of intensive short-term dynamic psychotherapy on pain catastrophizing and pain perception in women with breast cancer. Therefore, this therapy can be used alongside other medical treatment methods in hospitals and clinics dedicated to breast cancer patients to reduce the psychological needs and problems of women with this condition. [ABSTRACT FROM AUTHOR]

With the increasing prevalence of tumors, effective symptom management has emerged as a cornerstone of patient care. While surgical interventions remain pivotal, non-surgical nursing methods have gained prominence in providing relief from pain, discomfort, and other tumor-related symptoms. This review delves into the various non-surgical approaches employed, emphasizing tumor sedation and analgesia. We discuss the array of non-pharmacological and pharmacological strategies, shedding light on their indications, contraindications, and potential side effects. Furthermore, the importance of addressing individual differences in pain perception and the ethical considerations in symptom management are highlighted. We conclude by providing insights into the recent innovations in the field, emphasizing the need for personalized and comprehensive care to enhance patients’ quality of life. Tumor sedation, Tumor analgesia, Non-surgical nursing care, Pain management, Non-pharmacological interventions, Palliative care, Recent innovations, Symptom management. [ABSTRACT FROM AUTHOR]

Copyright of Agri: Journal of the Turkish Society of Algology / Türk Algoloji (Ağrı) Derneği'nin Yayın Organıdır is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The cold pressor test (CPT) involves cold water immersion of either the upper or lower limb(s) and elicits increases in sympathetic nervous activity (SNA), heart rate (HR), and mean arterial pressure (MAP) via stimulation of pain and cutaneous thermoreceptors. Greater pain perception during the CPT is associated with greater increases in SNA and more robust physiological responses. Due to potential differential sensitivity to both painful and thermal stimuli between upper and lower limbs, as well as potential effects of total exposure area, it is unclear whether the choice of limb(s) in CPT protocol design differentially affects systemic and cerebral hemodynamic responses. Our objective was to assess systemic and cerebral hemodynamic and ventilatory responses to different CPT protocols of the hand (CPTH), foot (CPTF), or bilateral feet (CPTBF). We hypothesized CPTBF would elicit greatest physiological responses due to increased exposure area to the cold stimulus. Twenty-eight (14 M, 14 F) healthy young adults [23.4 (SD: 2.4) yr] participated in three 3-min CPT protocols during a single visit. Blood pressure, HR, middle cerebral artery blood velocity (MCAv) and cerebrovascular conductance index, and end-tidal carbon dioxide (P ET CO 2 ) were averaged over the final 30 s of each minute of the CPT for each protocol, and perceived pain was recorded at the end of each minute of the CPT. We found significant effects of the time-CPT protocol interaction on systolic blood pressure (P = 0.02), diastolic blood pressure (P < 0.01), MAP (P < 0.01), and HR (P < 0.001). There were no differences between CPT protocols on either MCAv (P = 0.4) or cerebrovascular conductance index (P = 0.1). HR responses peaked in the first minute of the CPT, and changes from baseline were greater in CPTBF [Δ14(16) beats/min] compared with CPTH [Δ5(13) beats/min; P = 0.01] and CPTF [Δ4.04(13.3) beats/min; P = 0.02]. MAP responses peaked in minute 2 of the CPT, and changes from baseline were greater in CPTH [Δ12(8) mmHg) and CPTBF (Δ13(9) mmHg] compared with CPTF [Δ8(7) mmHg; P < 0.01]. Perceived pain was significantly greater in the CPTBF [CPT1 7(2.3), CPT2 6.5(2.3), CPT3 6(3)] condition compared with CPTH [CPT1 6(1.3), CPT2 6(2.3), CPT3 6(2.3)] and CPTF [CPT1 6(3.0), CPT2 6(2.0), CPT3 5.5(3.0)] protocols at all three stages of the CPT (P ≤ 0.01). Our findings suggest choice of limb(s) in CPT protocols may lead to differences in systemic hemodynamic responses, with pain perception potentially influencing these responses. Based on our results, we suggest that choice of limb should be considered in future design of CPT studies, with hand CPT providing the best balance between participant tolerability and robust physiological responses. NEW & NOTEWORTHY: Choice of limb(s) in cold pressor test (CPT) studies appears to influence systemic hemodynamics. Hand and bilateral feet induce more robust responses than single-foot CPT, potentially due to increased exposure area and pain perception. Despite no significant cerebrovascular effects, a sustained hyperventilatory response was noted in bilateral feet CPT. Hand CPTs may provide a balance between robust physiological responses and tolerability. These findings underscore the need for careful limb selection in future CPT studies. [ABSTRACT FROM AUTHOR]

Introduction: Having multiple pharmacological effects is a characteristic of Traditional Chinese Medicine (TCM). Currently, there is a lack of suitable methods to explore and discover modern diseases suitable for TCM treatment using this characteristic. Unsupervised machine learning technology is an efficient strategy to predict the pharmacological activity of drugs. This study takes Yuxuebi Tablet (YXB) as the research object. Using the unsupervised machine learning technology of drug cell functional fingerprint similarity research, the potential pharmacological effects of YXB were discovered and verified. Methods: LC-MS combined with the in vitro intestinal absorption method was used to identify components of YXB that could be absorbed by the intestinal tract of rats. Unsupervised learning hierarchical clustering was used to calculate the degree of similarity of cellular functional fingerprints between these components and 121 marketed Western drugs whose indications are diseases and symptoms that YXB is commonly used to treat. Then, based on the Library of Integrated Network-based Cellular Signatures database, pathway analysis was performed for selected Western drugs with high similarity in cellular functional fingerprints with the components of YXB to discover the potential pharmacological effects of YXB, which were validated by animal experiments. Results: We identified 40 intestinally absorbed components of YXB. Through predictive studies, we found that they have pharmacological effects very similar to non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. In addition, we found that they have very similar pharmacological effects to antineuropathic pain medications (such as gabapentin, duloxetine, and pethidine) and may inhibit the NF-B signaling pathway and biological processes related to pain perception. Therefore, YXB may have an antinociceptive effect on neuropathic pain. Finally, we demonstrated that YXB significantly reduced neuropathic pain in a rat model of sciatic nerve chronic constriction injury (CCI). Transcriptome analysis further revealed that YXB regulates the expression of multiple genes involved in nerve injury repair, signal transduction, ion channels, and inflammatory response, with key regulatory targets including Sgk1, Sst, Isl1, and Shh. Conclusion: This study successfully identified and confirmed the previously unknown pharmacological activity of YXB against neuropathic pain through unsupervised learning prediction and experimental verification. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene—specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774—and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Precisely selected patients require vitreoretinal surgeries (VRS) performed under general anesthesia (GA) when intravenous rescue opioid analgesics (IROA) are administered intraoperatively, despite a risk of adverse events, to achieve hemodynamic stability and proper antinociception and avoid the possibility of intolerable postoperative pain perception (IPPP). Adequacy of anesthesia guidance (AoA) optimizes the titration of IROA. Preventive analgesia (PA) techniques and intravenous or preoperative peribulbar block (PBB) using different local anesthetics (LAs) are performed prior to GA to optimize IROA. The aim was to analyze the utility of PBBs compared with intravenous paracetamol added to AoA-guided GA on the incidence of IPPP and hemodynamic stability in patients undergoing VRS. Methods: A total of 185 patients undergoing vitreoretinal surgery (VRS) were randomly assigned to one of several anesthesia protocols: general anesthesia (GA) with analgesia optimized through AoA-guided intraoperative remifentanil opioid analgesia (IROA) combined with a preemptive single dose of 1 g of paracetamol (P group), or PBB using one of the following options: 7 mL of an equal mixture of 2% lidocaine and 0.5% bupivacaine (BL group), 7 mL of 0.5% bupivacaine (BPV group), or 7 mL of 0.75% ropivacaine (RPV group). According to the PA used, the primary outcome measure was postoperative pain perception assessed using the numeric pain rating scale (NPRS), whereas the secondary outcome measures were as follows: demand for IROA and values of hemodynamic parameters reflecting quality or analgesia and hemodynamic stability. Results: A total of 175 patients were finally analyzed. No studied PA technique proved superior in terms of rate of incidence of IPPP, when IROA under AoA was administered (p = 0.22). PBB using ropivacaine resulted in an intraoperative reduction in the number of patients requiring IROA (p = 0.002; p < 0.05) with no influence on the dose of IROA (p = 0.97), compared to paracetamol, and little influence on hemodynamic stability of no clinical relevance in patients undergoing VRS under AoA-guided GA. Conclusions: PA using paracetamol or PBBs, regardless of LAs used, in patients undergoing VRS proved no advantage in terms of rate of incidence of IPPP and hemodynamic stability when AoA guidance for IROA administration during GA was utilized. Therefore, PA using them seems no longer justified due to the potential, although rare, side effects. [ABSTRACT FROM AUTHOR]

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The present study aimed to investigate the effects of dysfunctional attitudes on pain perception in migraine sufferers, considering the mediating role of fear of disease progression. 200 migraine sufferers who were referred to neurology clinics in Mashhad City, Iran, were included using the convenience sampling method. Data were collected using the Dysfunctional Attitudes Scale, McGill Pain, and Fear of Progression Questionnaire. Collected data were analyzed using Pearson's correlation test and structural equation modeling in SPSS and AMOS 21. The direct route of dysfunctional attitudes and fear of disease progression on pain perception as well as the direct route of dysfunctional attitudes on fear of disease progression were both positively significant (p <.001). Moreover, there was an indirect effect of dysfunctional attitudes on pain perception through the fear of the progression route in which 55% of the effect of dysfunctional attitudes on pain perception was attributed to the fear of disease progression. Dysfunctional attitudes may worsen pain perception in migraine sufferers, with fear of disease progression as a mediator. [ABSTRACT FROM AUTHOR]

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale—Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management. [ABSTRACT FROM AUTHOR]

The brain integrates information from pain-predictive cues and noxious inputs to construct the pain experience. Although previous studies have identified neural encodings of individual pain components, how they are integrated remains elusive. Here, using a cue-induced pain task, we examined temporal functional magnetic resonance imaging activities within the state space, where axes represent individual voxel activities. By analyzing the features of these activities at the large-scale network level, we demonstrated that overall brain networks preserve both cue and stimulus information in their respective subspaces within the state space. However, only higher-order brain networks, including limbic and default mode networks, could reconstruct the pattern of participants' reported pain by linear summation of subspace activities, providing evidence for the integration of cue and stimulus information. These results suggest a hierarchical organization of the brain for processing pain components and elucidate the mechanism for their integration underlying our pain perception. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Design Methods Results Conclusion Implications for the Profession and Patient Care Impact Reporting Method Patient or Public Contribution To identify and compare factors associated with pain perception and management among paediatric nurses and nursing students using virtual human technology.This study employed a comparative, cross‐sectional design.Fifty‐one paediatric nurses from a tertiary hospital and 50 senior nursing students from a nursing college, both located in South Korea, participated in the study. Virtual vignettes, including scenarios with virtual children and their clinical information, were used to assess participants' pain perception and management. The virtual children, created from real face photos, varied in age (young/old), sex (boy/girl) and facial expressions (smile/grimace). Participants rated perceived pain scores and selected management choices for eight virtual vignettes, which were randomly presented. The Korean version of the Paediatric Nurses' Knowledge and Attitude Survey was completed along with demographic information.Both paediatric nurses and nursing students rated pain scores lower than the actual pain scores reported by virtual children. Nurses rated higher pain scores and accordingly selected more medication doses compared to students. Beyond pain‐related knowledge, the facial expression of the virtual child influenced pain rating and medication choices, while age and sex had no effect.Nursing students were more sensitive to the facial expressions of virtual children when rating their pain compared to nurses. Future studies should explore how paediatric nurses' clinical experiences impact their assessment and management of child patient pain.Paediatric nurses' knowledge of pain is inadequate, necessitating ongoing education in pain management. Both nurses and nursing students should self‐reflect on their pain assessment practices to ensure unbiased care regardless of child patients' characteristics.Virtual human technology can be utilised to train nurses and students to identify and address any biases in their assessment of patients' pain perception.STROBE checklist, cross‐sectional.Digital face photos of four healthy children were used as the fundamental material for creating virtual children, with their parents' consent. [ABSTRACT FROM AUTHOR]

In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome "pain", as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9–15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training. [ABSTRACT FROM AUTHOR]

Pain, as a multidimensional and subjective experience, intertwines with various aspects of body representation, involving sensory, affective and motivational components. This review explores the bidirectional relationship between pain and body representations, emphasizing the impact of the sense of ownership on pain perception, the transformative impact of pain on motor imagery, the effects associated with vicarious pain perception on body representations and the role of pain in the maintenance of body representations in specific clinical conditions. Literature indicates complex interactions between pain and body representations, with the sense of ownership inducing analgesic effects in some cases and hyperalgesia in others, contingent upon factors such as the appearance of the affected limb. Pain sensations inform the body on which actions might be executed without harm, and which are potentially dangerous. This information impacts on motor imagery too, showing reduced motor imagery and increased reaction times in tasks where motor imagery involves the painful body parts. Finally, contrary to the conventional view, according to which pain impairs body representation, evidence suggests that pain can serve as an informative somatosensory index, preserving or even enhancing the representation of the absent or affected body parts. This bidirectional relationship highlights the dynamic and multifaceted nature of the interplay between pain and body representations, offering insights into the adaptive nature of the central nervous system in response to perceived bodily states. [ABSTRACT FROM AUTHOR]

Aim. The current review aims to explore postoperative neurological complications in third molar extractive surgery. Materials and Methods. The PRISMA protocols were followed when conducting this review. We found a total of 2,250 articles that matched our topic using the Boolean keywords, mandibular nerve complications AND oral surgery, from PubMed (1,083), Scopus (435), and Web of Science (732), with the filters of English language articles, time range January 1, 2003, to September 30, 2023, and human studies. After 762 duplicates were eliminated, there remained 1,488 articles. Eleven final articles were deemed of the highest relevance to our topic by eliminating articles in animals, non‐English language, reviews, meta‐analysis, and off‐topic. A potential risk in the third molar extraction was temporary loss of sensibility often caused by mild compression or irritation of the mandibular nerve. This typically resolves within weeks or months, but in severe cases, recovery might take longer. Permanent loss of sensation can occur, indicating significant nerve damage and lasting effects on touch, temperature, or pain perception. Conclusions. Various treatments exist for nerve damage, including low‐level laser therapy, pain management medications, or physical therapy. While these therapies may improve neurosensory impairment, patients often report a decline in their quality of life. [ABSTRACT FROM AUTHOR]

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3β domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3−/−, mice, indicating that the 1α3β, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors. The intracellular domain (ICD) of ion channels is crucial for the regulation of channel activity and signal transduction. Here the authors show that the P2X3 receptor's ICD can move in coordination with the transmembrane region and facilitate channel activation. [ABSTRACT FROM AUTHOR]

According to evolutionary psychologists, an individual-consciously or not-who allocates resources for somatic effort focuses on homeostasis and the protection of themselves and others. During health crises, patients must choose between mobilizing their remaining resources to either recover or accepting the disease as inevitable. When patients choose to be proactive in terms of protecting their health, are conscientious, and compliant in the recovery process, a high level of patient activation is achieved. Therefore, we examined (N=252) whether the patients' K fitness strategies are predictors for engagement in patient activation-type behavior. In addition, we tested the mediating effect of pain catastrophizing and the moderating effect of romantic satisfaction. We found that people with a medical diagnosis, who were in a romantic relationship, and had high-K fitness were much more likely to be activated patients. Moreover, pain catastrophizing mediated the relationship between high-K fitness strategy and patient activation, while romantic satisfaction moderated this relationship, amplifying its intensity. The findings highlight the importance of identifying patients' psychological resources (e.g., high-K strategy, romantic satisfaction, or pain perception) to keep them engaged in the health recovery process. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of laser phototherapy, Buzzy®, and lignocaine gel in minimizing pain during intraoral injections. Methods: In this randomized controlled trial, the efficacy of standard lignocaine gel (Group A) was compared with Buzzy * (Group B) and laser phototherapy (Group C) as pre-anesthetic agents in 15 children aged eight to 12 years undergoing intraoral local anesthesia (LA). Pain perception during needle insertion was assessed objectively using the Face, Legs, Activity, Cry, Consolability (FLACC) scale and subjectively using the Visual Analogue Scale (VAS). Statistical analysis included chi-square and analysis of variance tests (P<0.05). Results: Objective assessment of pain perception using FLACC scores demonstrated that Buzzy® resulted in the highest comfort levels; 60 percent of the subjects treated with Buzzy®, 40 percent treated with laser phototherapy, and 6.7 percent treated with lignocaine topical anesthetic were judged to be relaxed and comfortable or exhibiting mild discomfort, respectively. Subjective pain assessment (self-reported using the VAS) was significantly lower in Buzzy® (0.67±0.82 standard deviation) followed by laser phototherapy (1.00+1.13) and Lignocaine gel group (2.13+1.51). Conclusions: The Buzzy® and laser phototherapy effectively reduced intraoral injection pain compared to the standard control, lignocaine gel. However, Buzzy® showed better efficacy. [ABSTRACT FROM AUTHOR]