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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]

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]

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]

In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an "early long-term potentiation-like" sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats. High-frequency electrocutaneous stimulation alone induced enhanced perceptual responses to pinprick stimuli in cutaneous areas secondary to the area of electrical stimulation in humans and increased the excitability of spinal neurones which exhibited stimulus intensity-dependent coded responses to pinprick stimulation in a manner that tracked with human psychophysics, supporting their translational validity. Application of a distant noxious conditioning stimulus during HFS did not alter perceived primary or secondary hyperalgesia in humans or the development of primary or secondary neuronal hyperexcitability in rats compared with HFS alone, suggesting that, upon HFS-response initiation in a healthy nervous system, excitatory signalling escapes inhibitory control. Therefore, in this model, dampening facilitatory mechanisms rather than augmenting top-down inhibitions could prevent pain development. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) are neurodevelopmental disorders manifested mainly in children, with symptoms ranging from social/communication deficits and stereotypies to associated behavioral anomalies like anxiety, depression, and ADHD. While the patho-mechanism is not well understood, the role of neuroinflammation has been suggested. Nevertheless, the triggers giving rise to this neuroinflammation have not previously been explored in detail, so the present study was aimed at exploring the role of glutamate on these processes, potentially carried out through increased activity of inflammatory cells like astrocytes, and a decline in neuronal health. A novel chlorpyrifos-induced paradigm of ASD in rat pups was used for the present study. The animals were subjected to tests assessing their neonatal development and adolescent behaviors (social skills, stereotypies, sensorimotor deficits, anxiety, depression, olfactory, and pain perception). Markers for inflammation and the levels of molecules involved in glutamate excitotoxicity, and neuroinflammation were also measured. Additionally, the expression of reactive oxygen species and markers of neuronal inflammation (GFAP) and function (c-Fos) were evaluated, along with an assessment of histopathological alterations. Based on these evaluations, it was found that postnatal administration of CPF had a negative impact on neurobehavior during both the neonatal and adolescent phases, especially on developmental markers, and brought about the generation of ASD-like symptoms. This was further corroborated by elevations in the expression of glutamate and downstream calcium, as well as certain cytokines and neuroinflammatory markers, and validated through histopathological and immunohistochemical results showing a decline in neuronal health in an astrocyte-mediated cytokine-dependent fashion. Through our findings, conclusive evidence regarding the involvement of glutamate in neuroinflammatory pathways implicated in the development of ASD-like symptoms, as well as its ability to activate further downstream processes linked to neuronal damage has been obtained. The role of astrocytes and the detrimental effect on neuronal health are also concluded. The significance of our study and its findings lies in the evaluation of the involvement of chlorpyrifos-induced neurotoxicity in the development of ASD, particularly in relation to glutamatergic dysfunction and neuronal damage. [ABSTRACT FROM AUTHOR]

Understanding the endocannabinoid system in C. elegans may offer insights into basic biological processes and potential therapeutic targets for managing pain and inflammation in human. It is well established that anandamide modulates pain perception by binding to cannabinoid and vanilloid receptors, regulating neurotransmitter release and neuronal activity. One objective of this study was to demonstrate the suitability of C. elegans as a model organism for assessing the antinociceptive properties of bioactive compounds and learning about the role of endocannabinoid system in C. elegans. The evaluation of the compound anandamide (AEA) revealed antinociceptive activity by impeding C. elegans nocifensive response to noxious heat. Proteomic and bioinformatic investigations uncovered several pathways activated by AEA. Enrichment analysis unveiled significant involvement of ion homeostasis pathways, which are crucial for maintaining neuronal function and synaptic transmission, suggesting AEA's impact on neurotransmitter release and synaptic plasticity. Additionally, pathways related to translation, protein synthesis, and mTORC1 signaling were enriched, highlighting potential mechanisms underlying AEA's antinociceptive effects. Thermal proteome profiling identified NPR-32 and NPR-19 as primary targets of AEA, along with OCR-2, Cathepsin B, Progranulin, Transthyretin, and ribosomal proteins. These findings suggest a complex interplay between AEA and various cellular processes implicated in nociceptive pathways and inflammation modulation. Further investigation into these interactions could provide valuable insights into the therapeutic potential of AEA and its targets for the management of pain-related conditions. [ABSTRACT FROM AUTHOR]

Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (−4.5 ± 2.9 vs −3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia. [ABSTRACT FROM AUTHOR]

Objective Pain's impact on executive function is understood and specific cognitive abilities may contribute to coping with pain, though past work is confounded by chronic pain populations. This study aims to understand how executive functioning may predict the experience of pain among healthy adults. It was hypothesized that poorer executive functioning would predict more intense pain perception. Method A total of 172 young adults were recruited for participation. Three aspects of executive functioning (i.e. impulsivity, cognitive flexibility, working memory) were assessed before randomizing participants to varying types and levels of stimulated pain. Results Results supported the hypothesis that poorer performance on tasks of working memory predicts more intense pain perception. Conclusions Findings are counter to past work that has found inhibition may be important for coping, and future research is needed to understand the impact of specific cognitive abilities as well as how this may differ for chronic pain. [ABSTRACT FROM AUTHOR]

Purpose: Event-related desynchronisation (ERD) and event-related synchronisation (ERS) reflect pain perception and integration of the nociceptive sensory inputs. This may contribute to the understanding of how neurophysiological markers of Knee Osteoarthritis (KOA) patients can differ from control individuals, which would improve aspects such as prediction and prognosis. We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, compared with 65 control participants. The study aimed to examine possible differences between ERD and ERS in control participants compared to Knee Osteoarthritis (KOA) patients when adjusting for important covariates. Materials and methods: We performed independent multivariate regression models considering as dependent variables the power value related to ERD and ERS for four different sensorimotor tasks (Motor Execution, Motor Imagery, Active Observation and Passive Observation) and four sensorimotor oscillations (Alpha, Beta, Low Beta, and High Beta), each model, controlled by age and sex. Results: We demonstrate that the differences between KOA and healthy subjects are frequency specific, as most differences are in the beta bandwidth range. Also, we observed that subjects in the KOA group had significantly higher ERD and ERS. This may be correlated to the amount of lack of brain organisation and a subsequent attempt at compensation induced by KOA. Conclusions: Our findings strengthen the notion that subjects with KOA have a higher degree of brain plasticity changes that are also likely correlated to the degree of compensation and behavioural dysfunction. [ABSTRACT FROM AUTHOR]

The association between low back pain and lumbar spine local dynamic stability (LDS) appears to be modulated by if and how someone catastrophizes about pain, suggesting that the cognitive perceptions of pain may influence an individual's ability to control lumbar spine motion. Previous work also demonstrates that directing cognitive resources and attentional focus can influence movement performance. Therefore, we aimed to examine whether distracting attentional focus would influence lumbar spine LDS during repetitive flexion-extension movements. Sixteen participants performed repetitive spine flexion-extension movements under two baseline conditions (pre- and post-), and while attentional focus was distracted by either an external sensory stimulus or a cognitive-motor dual-task, both targeted at the hands. Lumbar spine LDS was examined over 30 continuous movement repetitions using maximum Lyapunov exponents. In comparison to both Baseline and Post-Baseline trials, the perceived mental workload was significantly elevated during the cognitive-motor dual-task trial but not the external sensory stimulus trial. The only statistically significant effect on LDS occurred in the Post-Baseline trial, where LDS was higher than in the cognitive-motor dual-task. In combination with previous work, these findings suggest that distracting attentional focus during repetitive lumbar spine flexion-extension movements does not have a negative influence on lumbar spine LDS. [ABSTRACT FROM AUTHOR]

Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. PubMed database was used with the title keyword combinations "{gender OR sex} AND osteoarthritis" plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 were reviewed for appropriateness. Globally, women account for 60% of people with osteoarthritis, with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, and amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. The recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine. [ABSTRACT FROM AUTHOR]

In the mammalian somatosensory system, polymodality is defined as the competence of some neurons to respond to multiple forms of energy (e.g., mechanical and thermal). This ability is thought to be an exclusive property of nociceptive neurons (polymodal C-fiber nociceptors) and one of the pillars of nociceptive peripheral plasticity. The current study uncovered a completely different neuronal sub-population with polymodal capabilities on the opposite mechanical modality spectrum (tactile). We have observed that several tactile afferents (1/5) can respond to cold in non-nociceptive ranges. These cells' mechanical thresholds and electrical properties are similar to any low-threshold mechano-receptors (LT), conducting in a broad range of velocities (Aδ to Aβ), lacking CGRP and TRPM8 receptors. Due to its density, cold-response range, speed, and response to injury (or lack thereof), we speculate on its role in controlling reflexive behaviors (wound liking and rubbing) and modulation of nociceptive spinal cord integration. Further studies are required to understand the mechanisms behind this neuron's polymodality, central architecture, and impact on pain perception. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals.Sixty‐three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut‐offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable.Significantly different OTA was observed among the anxiety subgroups (p = .003), supporting a decreased perception of thicknesses 24 and 32 μm (p = .018 and p < .001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p = .008), showing decreased perception of thicknesses 32 and 40 μm (p < .001 and p = .007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables.Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment. [ABSTRACT FROM AUTHOR]

Recent research has extensively explored the intricate mechanisms that underlie the effectiveness of acupuncture, highlighting the importance of stimulating acupoints, the role of acupuncture techniques in managing diseases, and the interaction between meridian pathways and molecular processes. Studies have underscored the crucial role of acupuncture in activating neurons, modulating the immune system, and influencing vascular activity, all of which contribute significantly to its therapeutic benefits across a wide range of symptoms and conditions. Utilization of imaging modalities enables the identification of changes in cerebral blood flow, brain function, and regional glucose metabolism following acupuncture sessions. The interstitial fluid circulation network within meridians adheres to specific laws that facilitate the transportation of materials. Acupuncture initiates the release of neurotransmitters, neuropeptides, and immune factors, impacting pain perception, inflammation, and physiological functions. It influences the complex neuro–endocrine–immune network by activating pathways involving the nervous system, the hypothalamic-pituitary-adrenal axis, and immune responses. Moreover, acupuncture induces molecular modifications such as phosphorylation, methylation, and histone modification, leading to key molecular changes that ultimately result in anti-inflammatory effects and the regulation of immune responses. [ABSTRACT FROM AUTHOR]

Objective: This Mendelian Randomization (MR) study aims to explore the potential causal relationships between four sleep traits and pain in 10 different body sites. Materials and methods: The study utilizes exposure and outcome data from the GWAS database, employing the Inverse Variance Weighting Method (IVW) for primary causal estimates. Cochran Q and Rücker Q heterogeneity tests are conducted using IVW and MR-Egger methods, with the Egger-intercept method for pleiotropy testing, leave-one-out sensitivity analysis, and calculation of F-statistics to assess the presence of weak instrument bias. Results: The study reveals that genetically predicted insomnia significantly increases the risk of unspecified pain, chest pain, gum pain, upper abdominal pain, and lower abdominal pain occurrence. Daytime napping is associated with a moderate reduction in the likelihood of joint pain but may concomitantly elevate the risk of chest pain, upper abdominal pain, and generalized abdominal pain. Neither sleep chronotype nor sleep duration demonstrated a definitive causal relationship with pain perception. Conclusion: This study elucidates the causal relationships between four sleep characteristics and pain across 10 different body regions. Overall, the contribution of insomnia and sleep deficiency to pain in multiple body regions is more pronounced. Conversely, the association between adequate sleep and the likelihood of somatic pain is relatively lower and less significant. [ABSTRACT FROM AUTHOR]

To compare the effectiveness, safety and patient satisfaction of a double balloon catheter (DB) with a synthetic osmotic cervical dilator (OD) for pre-induction cervical ripening in an outpatient setting.This is a prospective, dual-center pilot study including 94 patients with an unripe cervix (Bishop Score <6) near term; 50 patients received the DB and 44 patients the OD. The primary outcomes were the difference in Bishop Score (BS) and cervical shortening. Pain perception at insertion and during the cervical ripening period was evaluated by a visual analogue scale and patient satisfaction by a predefined questionnaire.The use of DB was associated with a significantly higher increase in BS (median 3) compared to OD (median 2; p=0.002) and resulted in significantly greater cervical shortening (median −14 mm vs. −9 mm; p=0.003). There were no serious adverse events at placement of devices or during the cervical ripening. There were no significant differences in perinatal outcomes. Pain perception during cervical ripening was significantly higher (p<0.001), and patient satisfaction regarding sleep, relaxing time and performing desired daily activities were significantly lower in patients with DB compared to patients with OD (p<0.001).DB was superior to OD regarding cervical ripening based on BS and on sonographic measurement of the cervical length. Patients with OD experienced less pain during cervical ripening and were more satisfied with the method compared to patients with DB. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution.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.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.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).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]

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50–150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) is an innovative technology with the potential to enhance treatment for children with chronic pain and functional symptoms. Currently, little is known about patients’ experiences of VR in the setting of intensive interdisciplinary pain treatment (IIPT). This study aimed to better understand how patients engage with and benefit from VR. This case report focuses on a 12-year-old female with amplified musculoskeletal pain syndrome and comorbid functional neurological disorder receiving treatment in inpatient IIPT. VR was incorporated into physical/occupational and recreational therapy sessions. A semi-structured interview was completed one-month post-discharge. Qualitative analysis revealed three major themes: Process of Change (VR was unique/immersive, reduced pain focus, challenged skepticism, and changed pain perception), Efficacy (VR increased movement, supported transitioning from a wheelchair to walking independently, and increased confidence, excitement, and surprise), and Engagement (VR aided in acknowledging progress, increased camaraderie, was fun, and challenged patient to extend treatment goals made in VR to real life). Therapist observations of the benefits and barriers to using VR in treatment are described. Overall, this report indicates that VR may be a helpful tool to use with existing IIPT interventions to enhance patient engagement in treatment and improve functionaloutcomes. [ABSTRACT FROM AUTHOR]

Pain perception is the consequence of a complex interplay between activation and inhibition. Noradrenergic pain modulation inhibits nociceptive transmission and pain perception. The main source of norepinephrine (NE) in the central nervous system is the Locus Coeruleus (LC), a small but complex cluster of cells in the pons. The aim of this study is to review the literature on the LC-NE inhibitory system, its influence on chronic pain pathways and its frequent comorbidities. The literature research showed that pain perception is the consequence of nociceptive and environmental processing and is modulated by the LC-NE system. If perpetuated in time, nociceptive inputs can generate neuroplastic changes in the central nervous system that reduce the inhibitory effects of the LC-NE complex and facilitate the development of chronic pain and frequent comorbidities, such as anxiety, depression or sleeping disturbances. The exact mechanisms involved in the LC functional shift remain unknown, but there is some evidence that they occur through plastic changes in the medial and lateral pathways and their brain projections. Additionally, there are other influencing factors, like developmental issues, neuroinflammatory glial changes, NE receptor affinity and changes in LC neuronal firing rates. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion To compare pain perception, pupil behaviours, and cytokine levels during first‐eye and second‐eye femtosecond laser‐assisted cataract surgery (FLACS) and determine which is better regarding a short or long interval for bilateral FLACS.Notably, 96 eyes of 48 patients with bilateral cataracts underwent the first surgeries in the left or right eye, according to a random sequence. They were further randomised into 2‐ and 6‐week subgroups based on surgery intervals. Pupil size was measured from captured images, and pain perception was assessed using a visual analog scale (VAS). Aqueous humour prostaglandin E2 (PGE2), monocyte chemoattractant protein‐1 (MCP‐1), interleukin (IL)‐6, and IL‐8 levels were also quantitatively analysed. All patients were followed for 1 week to evaluate changes in endothelial cell density (ECD), central corneal thickness (CCT), and macular central subfield thickness (CST).Ocular pain was significantly higher in patients who underwent second‐eye FLACS. First tear break‐up time was negatively correlated with VAS score. MCP‐1 levels were significantly higher in patients who underwent second‐eye FLACS, and VAS scores were positively correlated with MCP‐1 levels across all patients. There were no differences between sequential FLACS in miosis, PGE2, IL‐6, IL‐8 levels and changes in postoperative ECD, CCT, and CST. Patients who underwent second‐eye FLACS after 6 weeks showed more CCT, CST, and MCP‐1 changes than baseline.Second‐eye FLACS causes more pain and upregulated MCP‐1. There was no difference between sequential FLACS in PGE2 levels, miosis, and postoperative inflammation. Furthermore, first‐eye FLACS triggered a sympathetic irritation, particularly after a 6‐week interval. [ABSTRACT FROM AUTHOR]

Aims and Objectives Background Design Methods Results Conclusions Relevance to Clinical Practice To study the effects of virtual reality (VR) on pain perception among a paediatric population while being vaccinated. We will also investigate the effects of VR on the fear experienced by children during the vaccination procedure, as well as parental satisfaction levels.Many studies, for example, in the fields of oncology, dermatology or plastic surgery, have described the benefits of using VR to reduce the perception of pain among paediatric populations. These results are encouraging, but their main limitations were the small sample sizes they included or their methodological design.This will be a randomised clinical trial.SPIRIT guidelines were followed to report this protocol, and we will use the CONSORT and CONSORT‐EHEALTH guidelines to report the randomised clinical trial. The sample will comprise 148 children aged 3–14 years who will come for vaccination at the Tres Forques Health Center. The participants will be randomly allocated into intervention group (VR; n = 74) or (the control group standard‐of‐care; n = 74) at a 1:1 ratio. The intervention group will view experiences with a VR headset as a distraction measure. The study variables will be the level of pain and fear perceived by the child during vaccination, parental satisfaction with the vaccination procedure, and sociodemographic and vaccination variables.The start of the study is planned for September 2020, and the results will be expected in September 2021.This study aims to identify what measures reduce pain and fear in children during vaccination, which in turn, can help to improve the degree of parental satisfaction with these procedures.Vaccination is an independent function of the nursing profession. Identifying which distraction measures reduce the perception of pain and fear in the paediatric population will not only improve children's experiences but will also improve the satisfaction of both parents and children, thus increasing the degree of compliance with the vaccination schedule. [ABSTRACT FROM AUTHOR]

Substance P (SP) and a calcitonin‐related gene alpha (αCGRP−/−) are implicated in musculoskeletal pain perception and were shown to have different effects on the pathogenesis of osteoarthritis (OA). However, it has not been investigated, whether deficiency for SP or αCGRP impacts pain‐related behavior and well‐being as well as gait during development of experimental OA. We induced OA in the right knee of wild‐type (WT) mice and mice either deficient for SP (tachykinin 1, Tac‐1) or αCGRP (male, n = 8 per genotype) by destabilizing the medial meniscus (DMM). We monitored body weight and food and water intake as indicators of wellbeing, determined nest building and composite pain score, and performed CatWalk gait analysis over 12 weeks. Cartilage degeneration was determined by OARSI scoring. The 12‐week post‐DMM, cartilage degradation in the medial compartment was significantly reduced in Tac1−/− mice compared to the WT and to αCGRP−/− mice, coinciding with highest unloading of the operated limb in Tac1−/−. Behavioral and gait analysis revealed only minor differences between the genotypes. Paw print area was most prominently reduced in Tac1−/− over the observation period; at 12 weeks, we found a significant reduction in normalized print area in Tac1−/− compared to presurgery and to the WT at the same time‐point. Calculated weight bearing was significantly reduced only in Tac1−/−. Overall, we observed minor impact of DMM on gait and behavior in the present study. The reduced cartilage damage in the absence of SP might be in part due to reduced loading, however, the mechanism is not clear yet. [ABSTRACT FROM AUTHOR]

Introduction: There is an underuse of pain management strategies in dental care for children, possibly owing to perceived stress and discomfort when treating children, which has also been reported by dental students. The aim of this study was to explore how undergraduate dental students experience and understand pain related to dental treatment in children. Materials and Methods: Interviews were held with 21 Swedish dental students, from 3 dental schools, all in their final 2 years of education. The interviews were transcribed verbatim and analysed according to Grounded Theory. Results: A core category, seeking guidance to avoid pain, was identified and related to 6 conceptual categories. The students used different strategies to manage pain prevention in child dentistry and to become skilled dentists. They described high levels of stress, as well as having high expectations on themselves when treating children. The stress led to a surface learning approach, something the students were not fully aware of. Conclusion: All children should have the right to be ensured optimal pain prevention in dental care. The basis for this is laid during undergraduate education. Thus, pain management in child dentistry is an area in need of special attention in this respect. The academic staff has an important role in supporting their students in their process to gain an identity as professional dentists. To ensure that students incorporate an understanding of the importance of pain prevention when treating children there is a need to create more integration between theory and clinical training in undergraduate education. [ABSTRACT FROM AUTHOR]

Purpose: This randomized controlled trial aimed to ascertain the effect of a pre-procedure informational video on anxiety, pain perception, and satisfaction levels in patients undergoing amniocentesis. Methods: Patients were randomized into two groups: a video group who watched an informational video prior to the procedure, and a control group who received standard care. Anxiety was gauged both pre- and post-procedure via the State-Trait Anxiety Inventory (STAI) score. Post-procedure, patients' perceived pain, anxiety, and satisfaction levels were evaluated using the Visual Analog Scale questionnaire (VAS). Results: Of 110 randomized patients, 100 completed the study and were included in the final analysis. No significant difference was noted in overall anxiety levels between the study and control groups. However, in-procedure anxiety was significantly lower in the video group compared to the control group (p = 0.04). Among patients undergoing amniocentesis for the first time, the subgroup analysis revealed reduced levels of anxiety during the procedure and diminished pain 10 min after the procedure in the video group compared to the control group. (p = 0.041 and p = 0.025, respectively). Conclusion: A pre-procedural informational video could help in alleviating anxiety and mitigating pain during amniocentesis. Clinical trial registration: The study was registered at 27.3.2022 in clinical-trials.gov (identifier NCT05463549). [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to investigate the association between emotion regulation difficulties and pain perception during the immediate postpartum period. Methods: A cross-sectional study was performed in women during the immediate postpartum period. Women completed the Difficulties in Emotion Regulation Scale (DERS) questionnaire to measure difficulties in emotion regulation. A second analysis was conducted for the six subdomains of the DERS questionnaire. The visual analog scale (VAS) was used to measure pain intensity. The association between DERS scores and VAS score was assessed. Multivariable logistic regression models were constructed to control for potential confounders. Results: A total of 150 women were included in the final analysis, of whom 112 (74.6%) delivered vaginally and 38 (25.4%) had a cesarean delivery. Higher DERS scores, indicating more difficulties in emotion regulation, were significantly associated with higher VAS scores regardless of mode of delivery. Likewise, higher emotion regulation scores in 5 of 6 subdomains were associated with higher VAS scores (p < 0.001). Using multivariate logistic regression models higher DERS scores were independently associated with higher VAS scores. Conclusion: Difficulties in emotion regulation are associated with higher pain perception during the immediate postpartum period. Interventions designed to improve emotion regulation may improve maternal well-being in the immediate postpartum period and possibly reduce use of pain medication. [ABSTRACT FROM AUTHOR]

Background/Objective: Wound infiltration with local anesthetics emerges as a promising modality for postoperative pain alleviation. However, such strategies in neck surgery have not been a well-established practice. To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Methods: This prospective, double-blind, randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration, the study participants were randomly allocated into three groups: (1) 100 mg of ropivacaine (Group R); (2) 100 mg of ropivacaine plus magnesium sulfate 10 mg/kg (Group RMg); and (3) normal saline which served as a placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 min, as well as at 1, 2, 4, 6, 12, and 24 h postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 min before infiltration and 6 h and 24 h postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to the saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operation-, wound-, or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the RMg group. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and the analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery. [ABSTRACT FROM AUTHOR]

Background: Virtual reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and the patients' perception of chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity or vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and the perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves to be beneficial in minimizing the perceived length of chemotherapy sessions for lung cancer patients, enhancing their overall treatment experience. The intervention was found to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes. [ABSTRACT FROM AUTHOR]

Despite being widely assumed, the worsening impact of unpredictability on pain perception remains unclear because of conflicting empirical evidence, and a lack of systematic integration of past research findings. To fill this gap, we conducted a systematic review and meta-analysis focusing on the effect of unpredictability on pain perception. We also conducted meta-regression analyses to examine the moderating effect of several moderators associated with pain and unpredictability: stimulus duration, calibrated stimulus pain intensity, pain intensity expectation, controllability, anticipation delay, state and trait negative affectivity, sex/gender and age of the participants, type of unpredictability (intensity, onset, duration, location), and method of pain induction (thermal, electrical, mechanical pressure, mechanical distention). We included 73 experimental studies with adult volunteers manipulating the (un)predictability of painful stimuli and measuring perceived pain intensity and pain unpleasantness in predictable and unpredictable contexts. Because there are insufficient studies with patients, we focused on healthy volunteers. Our results did not reveal any effect of unpredictability on pain perception. However, several significant moderators were found, ie, targeted stimulus pain intensity, expected pain intensity, and state negative affectivity. Trait negative affectivity and uncontrollability showed no significant effect, presumably because of the low number of included studies. Thus, further investigation is necessary to clearly determine their role in unpredictable pain perception. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodResultsConclusion\nIMPLICATIONS FOR REHABILITATIONThis paper aims to understand the distinctive biopsychosocial aspects and patient perspectives on chronic low back pain in Lebanon, an Arab country with a unique and rich cultural heritage.Qualitative, semi-structured interviews with 12 Lebanese patients purposefully sampled from various governorates. The interviews included participants from different geographic areas and religions. The data underwent analysis through an inductive thematic approach guided by a bounded relativist ontology, a subjectivist epistemology, and a descriptive phenomenological framework. The coding process was managed by computer-assisted qualitative data analysis software (QSR NVivo version 12.0).The researchers identified and constructed two themes: (1) Chronic low back pain: understanding the impact, coping strategies, and communication patterns in lived experiences within the Lebanese context. This theme sheds light on the complexities of pain management and societal influences in Lebanon. (2) Explanatory model of patients living with chronic low back pain in Lebanon. This theme allowed an exploration of the multifaceted narratives of chronic low back pain.This study found that Lebanese individuals attribute chronic low back pain to biomedical factors despite some recognizing psychosocial elements. It emphasizes the need to educate patients on the biopsychosocial model, facilitate better care, and dispel misconceptions.The exploration of patients’ pain perception may provide an opportunity to better develop and design culturally sensitive pain neuroscience education material for Arab-speaking and Lebanese physical therapists.The rehabilitation process should incorporate a balanced biopsychosocial approach, addressing both physical and psychosocial elements of pain, to provide more effective care and outcomes for Lebanese patients who predominantly attribute chronic low back pain to biomedical factors.Lebanese healthcare professionals need to improve communication with Lebanese patients regarding the nature of chronic low back pain, using clear communication to help dispel misconceptions and enhance rehabilitation outcomes.The exploration of patients’ pain perception may provide an opportunity to better develop and design culturally sensitive pain neuroscience education material for Arab-speaking and Lebanese physical therapists.The rehabilitation process should incorporate a balanced biopsychosocial approach, addressing both physical and psychosocial elements of pain, to provide more effective care and outcomes for Lebanese patients who predominantly attribute chronic low back pain to biomedical factors.Lebanese healthcare professionals need to improve communication with Lebanese patients regarding the nature of chronic low back pain, using clear communication to help dispel misconceptions and enhance rehabilitation outcomes. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and formalin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins. [ABSTRACT FROM AUTHOR]

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management. [ABSTRACT FROM AUTHOR]

Introduction: Nearly, a quarter of older adults suffer from frequent foot pain, impacting their quality of life. While proper footwear can alleviate this, design issues often hinder regular use. This study evaluated novel therapeutic footwear, designed for aesthetics and custom fit, to reduce foot pain. We hypothesized that older adults would experience less foot pain and favor the new footwear over their own. Methods: This 12-week crossover randomized controlled trial evaluated the effectiveness of OrthoFeet therapeutic footwear on reducing foot pain in older adults (n = 50, age = 65 ± 5, 18% male) with moderate to severe pain. Participants were assigned to either the AB or BA sequence. In AB, they wore OrthoFeet shoes for 6 weeks and then their own shoes for another 6 weeks; BA followed the reverse order. Pain and function were measured using the Foot Function Index. Acceptability was assessed through a technology acceptance model (TAM) questionnaire. Data collected at baseline, six, and 12 weeks were analyzed using t tests, χ2 tests, and generalized linear model. Results: Compared to participants' own shoes, OrthoFeet shoes significantly reduced foot pain and disability. Notable improvements were observed in "foot pain at its worst," "foot pain at the end of the day," "overall pain score," and "overall Foot Function Index score," all showing statistically significant reductions (p < 0.050). Participants reported high adherence to wearing the OrthoFeet shoes, averaging 8 h per day and 5.8 days per week. TAM scores favored OrthoFeet shoes over participants' own shoes in terms of ease of use, perceived benefit, and intention to recommend. Significant differences were noted in components representing perceived joint pain relief (p < 0.001, χ2 = 21.228) and the intention of use as determined by the likelihood of recommending the shoes to a friend with a similar condition (p < 0.001, χ2 = 29.465). Additionally, a majority of participants valued the appearance of the shoes, with 66% prioritizing shoe appearance and 96% finding the study shoes more stylish than their previous ones. Conclusion: This study underscores the significance of design and custom fit in promoting continuous wear for effective foot pain reduction in older adults. More research is needed on the intervention's long-term impacts. [ABSTRACT FROM AUTHOR]

Background: Symptomatic irreversible pulpitis often results in heightened reactions to thermal stimuli such as pain evoked by a cold stimulus, and spontaneous odontogenic pain (unprovoked pain). Objective: This study primarily compared the clinical manifestations of odontogenic spontaneous pain and pain provoked by cold stimulus specifically focusing on their sensory discriminative characteristics (intensity, duration and quality) between symptomatic irreversible pulpitis patients with and without referred pain. Methods: Twenty‐three patients with symptomatic irreversible pulpitis with referred pain and 12 patients without referred pain were included in this cross‐sectional study. The following outcomes were assessed: odontogenic spontaneous pain and its descriptors; pain evoked by cold stimulus and qualitative sensory testing before and after local anaesthesia; referred pain location; use of analgesic medication; complementary anaesthesia efficacy. T‐test, chi‐squared and McNemar tests were applied to the data (p <.50). Results: Patients with referred pain presented a greater odontogenic pain intensity (p <.05) when considered the average of the last 24 h. These patients also showed higher pain rating and pain descriptors (p <.05). Intensity and duration of the pain evoked by cold stimulus in the non‐affected contralateral tooth at baseline were higher for patients with referred pain (p <.05). Conclusion: Symptomatic irreversible pulpitis patients with referred pain present greater odontogenic spontaneous pain and a heightened pain sensitivity. Therefore, patients with referred pain seem more complex from a pain severity perspective, supporting the clinical utility of discriminating symptomatic irreversible pulpitis with and without referred pain. [ABSTRACT FROM AUTHOR]

Our laboratory previously developed a method for assessing experimentally induced pain perception through a 2-min constant heat pain stimulation. However, the traditional analysis relying on group means struggles to interpret the considerable inter-individual variability due to the dynamic nature of the response. Recently, trajectory analysis techniques based on extended mixed models have emerged, providing insights into distinct response profiles. Notably, these methods have never been applied to pain paradigms before. Furthermore, various socio-demographic and neurobiological factors, including endocannabinoids, may account for these inter-individual differences. This study aims to apply the novel analysis to dynamic pain responses and investigate variations in response profiles concerning socio-demographic, psychological, and blood endocannabinoid concentrations. 346 pain-free participants were enrolled in a psychophysical test involving a continuous painful heat stimulation lasting for 2 min at a moderate intensity. Pain perception was continuously recorded using a computerized visual scale. Dynamic pain response analyses were conducted using the innovative extended mixed model approach. In contrast to the traditional group-mean analysis, the extended mixed model revealed three pain response trajectories. Trajectory 1 is characterized by a delay peak pain. Trajectory 2 is equivalent to the classic approach (peak pain follow by a constant and moderate increase of pain perception). Trajectory 3 is characterized by extreme responses (steep peak pain, decrease, and increase of pain perception), Furthermore, age and blood anandamide levels exhibited significant variations among these three trajectories. Using an innovative statistical approach, we found that a large proportion of our sample had a response significantly different from the average expected response. Endocannabinoid system seems to play a role in pain response profile. [ABSTRACT FROM AUTHOR]

Background: Quantitative sensory tests (QST) are frequently used to explore alterations in somatosensory systems. Static and dynamic QST like pain threshold and temporal summation (TS) and conditioned pain modulation (CPM) are commonly used to evaluate excitatory and inhibitory mechanisms involved in pain processing. The aim of the present study was to document the reliability and the minimal detectable change (MDC) of these dynamic QST measurements using a standardized experimental paradigm. Material and methods: Forty-six (46) pain-free participants took part in 2 identical sessions to collect TS and CPM outcomes. Mechanical (pressure pain threshold [PPT]) and thermal (constant 2-minute heat pain stimulation [HPS]) nociceptive stimuli were applied as test stimuli, before and after a cold-water bath (conditioning stimulus). TS was interpreted as the change in pain perception scores during HPS. CPM were determined by calculating the difference in pain perception between pre- and post- water bath for both PPT and HPS. Relative and absolute reliability were analyzed with intra-class correlation coefficient (ICC2, k), standard error of the measurements (SEMeas) and MDC. Results: Results revealed a good to excellent relative reliability for static QST (ICC ≥ 0.73). For TS, a poor to moderate relative reliability depending on the calculation methods (ICC = 0.25 ≤ ICC ≤ 0.59), and a poor relative reliability for CPM (ICC = 0.16 ≤ ICC ≤ 0.37), both when measured with mechanical stimulation (PPT) and thermal stimulation (HPS). Absolute reliability varied from 0.73 to 7.74 for static QST, 11 to 22 points for TS and corresponded to 11.42 points and 1.56 points for thermal and mechanical-induced CPM, respectively. MDC analyses revealed that a change of 1.58 to 21.46 point for static QST, 31 to 52 points for TS and 4 to 31 points for CPM is necessary to be interpreted as a real change. Conclusion: Our approach seems well-suited to clinical use. Although our method shows equivalent relative and absolute reliability compared to other protocols, we found that the reliability of endogenous pain modulation mechanisms is vulnerable, probably due to its dynamic nature. [ABSTRACT FROM AUTHOR]

The importance of incorporating lumbo-pelvic stability core and controlling motor exercises in patients with chronic low back pain (CLBP) reinforces the use of strategies to improve biopsychosocial beliefs by reducing biomedical postulations. However, clinical practice guidelines recommend multimodal approaches incorporating exercise and manual therapy (MT), and instead reject the application of kinesiotape (KT) in isolation. Therefore, the objectives of this study were to analyze the effects of 12 weeks of exercises combined with MT or KT on perceived low back pain using the visual analog scale (VAS) and muscle electric activity measured with electromyography (EMG) of the rectus abdominis and multifidus in CLBP (mild disability) and to explore the relationship between the rectus abdominis and multifidus ratios and pain perception after intervention. A blinded, 12-week randomized controlled trial (RCT) was carried out, involving three parallel groups of patients with CLBP. The study was registered at Clinicaltrial.gov and assigned the identification number NCT05544890 (19/09/22). The trial underwent an intention-to-treat analysis. The primary outcome revealed a multimodal treatment program supplemented by additional therapies such as MT and KT, resulting in significant reductions in perceived low back pain. The subjective assessment of individuals with CLBP indicated no discernible distinction between exclusive core stability exercises and control-motor training when combined with MT or KT. Notably, our findings demonstrated positive alterations in both the mean and peak EMG values of the right rectus abdominis in the exercise group, suggesting a beneficial impact on muscle activation. This study focused on assessing the activation levels of the trunk musculature, specifically the rectus abdominis (RA) and multifidus (MF), in individuals with CLBP exhibiting mild disability according to the Oswestry Disability Index. Importantly, improvements in the VAS values were observed independently of changes in muscle electrical activity. [ABSTRACT FROM AUTHOR]

Pain recognition for culturally diverse people is complex as pain experience is subjective and influenced by cultural background. We compared the prevalence, intensity, and association of pain with neuropsychiatric symptoms (NPS) between immigrants and non-immigrants living with dementia in residential aged care homes (RACHs) who were referred to two Dementia Support Australia programs. Immigrant status was defined by the documented country of birth. Pain and NPS were assessed using PainChek® and the Neuropsychiatric Inventory, respectively. Subgroup analyses were also completed for English-speaking and non-English-speaking immigrants. A total of 17,637 referrals [immigrants, n = 6340; non-immigrants, n = 11,297] from 2792 RACHs were included. There were no significant differences for the prevalence of pain across all groups. Immigrants were slightly more likely to have moderate pain or severe pain than non-immigrants. Non-English-speaking immigrants had 0.5 points higher total pain scores on average (Cohen's d = 0.10 [0.05, 0.15], p < 0.001) than non-immigrants. Total pain score had a significant effect on total NPS severity scores in all groups. While pain prevalence is similar across groups, higher pain intensities are more common among immigrants living with dementia. Increased care staff awareness, education, and training about the potential effect of culture on pain expression is needed. [ABSTRACT FROM AUTHOR]

Summary Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain‐sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS. [ABSTRACT FROM AUTHOR]

Introduction: Chronic anxiety is a statemarked by sustained activation of the masseter muscle, manifesting in both mental and physical strain. This prolonged tension can significantly impact mental wellbeing and cognitive abilities, posing a risk for a range of health complications. This double-blind, randomized, controlled clinical trial investigated the impact of transcutaneous auricular vagus nerve stimulation (TAVNS) on masseter muscle activity, pressure pain threshold (PPT), and anxiety levels in university students with elevated anxiety. Methods: Forty-two participants meeting inclusion criteria were randomly assigned to either active TAVNS or sham TAVNS groups. Various parameters, including masseter muscle electromyographic (EMG) signals, PPT, and Beck Anxiety Inventory (BAI) scores, were assessed before pretreatment, immediately after the intervention week, and 2 weeks follow-up. Results: Active TAVNS significantly reduced both left and right masseter activation during resting mandibular position, persisting for 2 weeks post-intervention. Additionally, TAVNS induced a lasting decrease in both left and right masseter PPT, indicative of altered pain perception. Notably, BAI scores showed a substantial reduction, emphasizing TAVNS as a potential intervention for anxiety, with effects maintained at the 2-week follow-up. Discussion: This study provides comprehensive insights into the multifaceted effects of TAVNS on physiological and psychological aspects associated with anxiety in university students. The promising results underscore TAVNS as a potential neuromodulatory intervention for anxiety-related conditions, warranting further research and clinical exploration. [ABSTRACT FROM AUTHOR]

Pain can be conceptualized as a precision signal for reinforcement learning in the brain and alterations in these processes are a hallmark of chronic pain conditions. Investigating individual differences in pain-related learning therefore holds important clinical and translational relevance. Here, we developed and externally validated a novel resting-state brain connectivity-based predictive model of pain-related learning. The pre-registered external validation indicates that the proposed model explains 8-12% of the inter-individual variance in pain-related learning. Model predictions are driven by connections of the amygdala, posterior insula, sensorimotor, frontoparietal, and cerebellar regions, outlining a network commonly described in aversive learning and pain. We propose the resulting model as a robust and highly accessible biomarker candidate for clinical and translational pain research, with promising implications for personalized treatment approaches and with a high potential to advance our understanding of the neural mechanisms of pain-related learning. A predictive model based on brain connectivity was developed to explain individual differences in pain learning. Focusing on brain regions linked to aversive learning and pain, this model shows promise as a biomarker in translational pain research. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed. Objective: This study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified. Methods: A total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses. Results: Compared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio. Conclusion: MiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia syndrome (FMs) is a chronic condition characterized by widespread musculoskeletal pain and a range of complex symptoms, with chronic fatigue being a central feature significantly impacting daily life. The aim of this study was to analyze the secondary outcomes, specifically those related to perceived energy and fatigue symptoms in a randomized controlled trial (RCT) assessing the efficacy of heart rate variability biofeedback (HRV-BF) as an adjunctive treatment for FMs. Methods: Sixty-four FMs patients were randomly assigned to either receive 10 HRV-BF training sessions alongside standard pharmacological therapy (experimental group) or standard therapy alone for 10 weeks (control group). For this secondary analysis, potential improvements in specific items were evaluated regarding perceived energy (Item 10 of the Short-Form Health Survey), the ability to walk and climb stairs (Item 7 and Item 11 of the Fibromyalgia Impact Questionnaire, respectively), and the impact of pain on movement ability (Item 17 of the Bodily and Emotional Perception of Pain). Results: The experimental group demonstrated an improvement in the perception of energy, the ability to walk, and the impact of pain on movement ability. However, the same improvement was not observed in the ability to climb stairs. Conclusions: Fatigue assessment has emerged as a crucial factor for evaluating treatment efficacy in FMs and related conditions linked to altered energy levels, such as bipolar depression, and can offer valuable insights for precisely guiding HRV-BF treatments. ClinicalTrials.gov with code: NCT04121832. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation. [ABSTRACT FROM AUTHOR]

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional. [ABSTRACT FROM AUTHOR]

Summary Acute sleep deprivation in experimental studies has been shown to induce pain hypersensitivity in females. However, the impact of natural sleep deficiency and fluctuations across the week on pain perception remains unclear. A sleep‐monitoring headband and self‐reports were utilized to assess objective and subjective sleep in longer (> 6 hr) and short sleepers (< 6 hr). Pain sensitivity measures including heat, cold, pressure pain thresholds, pain inhibition (conditioned pain modulation) and facilitation (tonic pain summation) were assessed on Mondays and Fridays. Forty‐one healthy young (23.9 ± 0.74 years) women participated. Short sleepers slept on average 2 hr less than longer sleepers (297.9 ± 8.2 min versus 418.5 ± 10.9 min) and experienced impaired pain inhibitory response (mean = −21.14 ± 7.9°C versus mean = 15.39 ± 9.5°C; p = 0.005). However, no effect was observed in pain thresholds and pain summation (p > 0.05). Furthermore, pain modulatory responses differed between Mondays and Fridays. Chronic sleep deficiency (< 6 hr) compromises pain responses, notably on Mondays. Maintaining a consistent sleep pattern with sufficient sleep (> 6 hr) throughout the week may protect against pain sensitization and the development of chronic pain in females. Further research is needed, especially in patients with chronic pain. [ABSTRACT FROM AUTHOR]