Search

The mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context-specific changes in descending pain modulation.We compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain.Thermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p lt; 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects.Our data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context.Decrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.

BACKGROUND: Understanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in 'adaptive coding' of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs. METHODS: A cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively. RESULTS: The left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal. CONCLUSIONS: The study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain. SIGNIFICANCE: Although there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.

This study aimed to evaluate the effect of photobiomodulation therapy (PBMT) with 915 nm wavelength on pain reduction during maxillary incisors' local infiltration in a randomized clinical trial study. A prospective triple-blinded split-mouth clinical trial was designed to assess pain perception during needle insertion and local anesthetic injection in 32 healthy patients required operative caries management on contralateral maxillary incisors. After laser treatment (915 nm, power of 1.5 W, duty cycle of 60% and energy density of 72 J cmlt;supgt;-2lt;/supgt; ) in active group and no irradiation in sham group, the injection was performed. Patients' perception of pain was immediately assessed using numerical rating scale (NRS) for pain. Washout period between two appointments was one week. Wilcoxon signed-rank and Pearson correlation statistical analyses were used to assess the comparison of pain score between two appointments and the effect of anxiety level of previous dental injections. The mean scores of pain for the active laser and sham laser groups were 2.5 ± 2.19 and 4.34 ± 2.52, respectively, with a statistically significant higher NRS in the sham laser group (P ˂ 0.05). In this study's condition, diode PBMT reduced pain during infiltration on maxillary incisors. Anxiety experience of dental injection had no significant effect on pain perception scale (P ˃ 0.05).

Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat.Twenty-two patients with chronic oral burning pain underwent testing with a variety of olfactory and gustatory substances (pleasant, neutral, unpleasant) in multisensory interaction. The order of testing was randomized. Perception of pain intensity and unpleasantness was evaluated on a numerical rating scale at baseline and immediately after each test trial.Pain unpleasantness but not pain intensity was found to be modulated by chemosensory stimuli. Unpleasant olfactory and gustatory stimuli increased the perception of pain unpleasantness compared to pleasant and neutral stimuli. Pain unpleasantness after unpleasant olfactory and gustatory stimuli correlated with psychological questionnaire subscale scores for distress (CORE-OM) and emotional awareness (TAS-20).Our findings suggest a role of unpleasant chemosensory stimuli in increasing the perception of pain unpleasantness in patients with chronic oral burning. The lack of an effect on pain intensity indicates a dissociation between sensory and affective pain components. Future research is needed to further study the association between chemosensory stimuli and emotional and subjective aspects in modulating chronic oral burning pain.This exploratory work suggests that unpleasant smell and taste stimuli may have an adverse effect on the affective component of chronic oral burning pain. Future comprehensive large-scale research, also applying brain imaging investigations as well as full psychological analysis, is required to better understand the role of smell and taste stimuli on this chronic and disabling pain condition.

To evaluate the impact of photobiomodulation therapy (PBMT) on injection pain perception and compare it with a topical oral anesthetic gel. A total of 30 patients of 6 to 9 years-old seeking pulpotomy treatment of maxillary secondary primary molars of both sides were considered for this split-mouth triple-blind randomized clinical trial. On one side of the maxilla, the low-level laser (diode laser, 808 nm, 250 mW; 16.25 J; 32.5 J cm

BACKGROUND AND OBJECTIVES This study aimed to investigate the association between pain perception and catastrophizing at the beginning of orthodontic treatment; and the association between pain during orthodontic treatment and demographic, clinical, and other psychological factors. METHODS A cohort study with 44 patients (28.9±15.05 years old; 25 females and 19 males) under orthodontic treatment with fixed appliances had their pain perception evaluated through a visual analog scale at baseline (before activation), 6 h, 24 h, 2nd day, 3rd day, 5th day, and 7th day after activation. The scores at each evaluation period after the first (T1), second (T2), and third (T3) appointments were compared by analysis of variance. A multivariate Poisson regression analysis verified the association between pain perception and Pain Catastrophizing Scale (PCS); and demographic (age, gender), clinical (tooth crowding, tooth loss, analgesic intake, and archwire characteristics), and other psychological (dental anxiety, and previous negative dental experiences) independent variables (p

Objective To describe neurologic signs, diagnostic imaging findings, potential treatments, and outcomes in dogs with subaxial cervical articular process subluxation and dislocation, or a "locked facet." Study design Retrospective case series. Animals Ten client-owned dogs. Methods Dogs with a diagnosis of cervical locked facets were identified through medical records and imaging reports searches. Data on presenting signs, diagnostic findings, treatment, and outcome were recorded. Results All cases were small or toy-breed dogs with preceding trauma. Four dogs were tetraplegic with intact pain perception, five were nonambulatory tetraparetic, and one was ambulatory tetraparetic, with half of the tetraparetic dogs having worse motor function in the thoracic limbs. The only sites affected were C5/6 (n = 6) and C6/7 (n = 4). All dogs had unilateral dorsal displacement of the cranial articular process of the caudal vertebra relative to the caudal articular process of the cranial vertebra at the luxation site. Five dogs were treated surgically, three by external coaptation, one by restriction, and one was euthanized the day after diagnosis. All dogs with outcome data (n = 8) became ambulatory. Nonambulatory dogs returned to ambulation in a median of 4 weeks (IQR 1-12; range 1-28). Conclusion In these dogs, locked facet injuries affected the caudal cervical vertebrae in small breeds and could be identified on imaging through the presence of dorsal displacement of a cranial articular process. Our small cohort had a functional recovery regardless of treatment. Clinical signiicance Locked facet injuries should be a differential for small or toy-breed dogs with a cervical myelopathy secondary to trauma.

Exercise-induced hypoalgesia (EIH) is characterized as the pain reduction after an exercise session and it seems to be related to the release of plasma β-endorphin. In this sense, the core stabilization training (CT) has been suggested for patients with chronic nonspecific low back pain (CNSLBP), but it is unclear whether it induces EIH. Patients with CNSLBP have neuromotor dysfunctions that can affect the performance of functional tasks, thus, performing functional training (FT) could improve motor control and promote EIH, since functional training uses multi-joint exercises that aim to improve the functionality of actions performed in daily life. EIH is usually assessed using quantitative sensory tests (QST) such as conditioned pain modulation, pressure pain threshold, and temporal summation. Thus, the sum of parameters from quantitative sensory tests and plasma β-endorphin would make it possible to understand what the neuroendocrine effects of FT and CT session are. Our study compared the acute effect of CT and FT on the EIH and plasma β-endorphin release, and correlated plasma β-endorphin with quantitative sensory testing in patients with CNSLBP. Eighteen women performed two training sessions (CT and FT) with an interval of 48 h between sessions. EIH was assessed by QST and plasma β-endorphin levels. Results showed that only FT significantly increased plasma β-endorphin (FT p 0.01; CT p = 0.45), which correlated with pain pressure threshold (PPT) and conditioned pain modulation (CPM). However, QST values were not different in women with CNSLBP after CT or FT protocols. Plasma β-endorphin correlated with PPT and CPM, however, the same did not occur with a temporal summation.

Offset analgesia (OA) is characterized by a disproportionately large decrease in pain perception after a slight decrease in noxious stimulation. In patients with ongoing pain, this response is reduced. The effect is pronounced in painful body areas. The influence of acute pain has not been sufficiently investigated. The aim of this study was to investigate the influence of two experimental acute pain models, measured within the area of acute pain and on the non-affected opposite side, thereby considering the possible somatotopic nature of OA.Healthy, pain-free volunteers (n = 75) were randomly assigned to one of three groups (cold water, exercise and control group). The 'cold water group' immersed one hand into cold water for 3 min (Cold Pressor Task), while the 'exercise group' performed an isometric grip exercise for 3 min. There was no manipulation in the control group. Each experimental pain stimulus was performed at both (dominant, non-dominant) forearms. The individualized OA paradigm consisted of offset and constant temperature trials. Offset analgesia was measured immediately before, during and after the experimental pain stimuli.A significant difference in OA was shown during experimental pain when compared to the control condition (exercise vs. control: p 0.001, cold vs. control: p = 0.001), with no difference between the experimental conditions (p 0.05). Immediately following the pain stimulation, results were marginally non-significant (p = 0.05).Experimental painful stimulation reduced OA. This result should be interpreted with caution due to potential influences of conditioned pain modulation or exercise-induced hypoalgesia as well as possible floor effects.Temporal contrast of pain perception is inhibited in acute pain states. This study showed that reduced offset analgesia is observed when pain is experimentally induced using noxious cold and exercise stimuli.

Background Several methods including vibration have been proposed for pain control during a local anaesthetic injection. This study was aimed to evaluate the scientific evidence on vibration devices used to reduce injection pain perception in children. Methods The search terms were chosen according to the Medical Subject Headings MeSH and non-MeSH. Potentially eligible studies involved the subjective or objective pain evaluation in children receiving any type of dental injection. An electronic search of published studies in English language was carried out in March 2020 on Scopus, Cochrane, and PubMed databases.Of 1659 articles retrieved initially, 14 were eligible to be included in the systematic review, of which eight articles were excluded. The vibration devices used in the studies included Buzzy or DentalVibe. Four studies using Dentalvibe contributed to the meta-analysis. Results The results of meta-analysis indicated a mean difference of 0.057 for FLACC pain scores between intervention and control conditions (P-value = 0.740). Wong-Baker Faces scores showed a mean difference of 0.009 (P-value = 0.964), which also showed no statistically significant difference between the intervention and control groups. Conclusions The findings revealed that use of DentalVibe for Paediatric dental injections was not effective in reducing pain perception. However, use of Buzzy showed promising results.

OBJECTIVES: Multisite pain remains significantly understudied following lower-limb loss (LLL), especially among females. This study aimed to explore sex-specific differences in the presentation of multisite pain post-LLL. Hypotheses were multisite pain would be more prevalent among females post-LLL as compared to males, and female sex would be significantly associated with multisite pain prevalence. METHODS: In this cross-sectional study, participants answered standardized questions regarding the presence of amputation-specific (i.e., phantom limb, residual limb) and secondary (i.e., contralateral limb, low back) pain. Multisite pain was defined as pain in ≥2 locations. Sex-specific differences in pain prevalence were evaluated using chi-square tests (p≤.050). Using logistic regression, the association between sex and multisite pain was examined after controlling for covariates (age, body mass index, time since amputation, amputation etiology and level). RESULTS: The sample included 303 adults (33% females) ≥1-year post-unilateral LLL. More females than males reported pain in the residual limb (53.0% versus 38.4%), low back (56.0% versus 39.9%), contralateral knee (37.0% versus 24.1%), and contralateral hip (25.0% versus 12.3%) [p

Background: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. Methods: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). Results: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. Conclusions: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. Significance: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.

AIM The purpose is to investigate pain perception during transvaginal four-dimensional hysterosalpingo-contrast sonography (TV 4D-HyCoSy) and factors influencing pain severity. METHODS This was a retrospective study included 340 women who underwent TV 4D-HyCoSy examination from January 2016 to October 2017. The factors were recorded, including age, childbearing history, infertility type, history of pelvic inflammation, pelvic surgery, history of uterine manipulation, history of ectopic pregnancy, atropine delivery mode, uterine position, uterine malformation, uterine lesion, fibroid, intrauterine adhesion, polycystic ovary, endometrial implantation cyst, dysmenorrhea score, the degree of patency of fallopian tube and contrast agents dosage. Pain was evaluated during and after TV 4D-HyCoSy. The time point of peak pain was evaluated and the influencing factors of moderate/severe pain were analyzed. RESULTS The highest pain occurred at contrast instillation. The independent influencing factors of moderate/severe pain were age (P = 0.021), dysmenorrhea score (P = 0.003) and tubal patency (P

KEY POINTS Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans. ABSTRACT Low dose ketamine is an effective analgesic medication. However, our knowledge of the effects of ketamine on autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low dose ketamine influences autonomic cardiovascular responses during painful stimuli in humans. We tested the hypothesis that low dose ketamine blunts perceived pain, and blunts subsequent sympathetic and cardiovascular responses during an experimental noxious stimulus. Twenty-two adults (10F/12M; 27 ± 6 years; 26 ± 3 kg m-2 , mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed cold pressor tests (CPT; hand in ∼0.4°C ice bath for 2 min) pre- and 5 min post-drug administration (20 mg ketamine or saline). We compared pain perception (100 mm visual analogue scale), muscle sympathetic nerve activity (MSNA; microneurography, 12 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) during the pre- and post-drug CPTs separately using paired, two-tailed t tests. For the pre-drug CPT, perceived pain (P = 0.4378), MSNA burst frequency responses (P = 0.7375), and mean BP responses (P = 0.6457) were not different between trials. For the post-drug CPT, ketamine compared to placebo administration attenuated perceived pain (P

Neural dynamics can shape human experience, including pain. Pain has been linked to dynamic functional connectivity within and across brain regions of the dynamic pain connectome (consisting of the ascending nociceptive pathway (Asc), descending antinociceptive pathway (Desc), salience network (SN), and the default mode network (DMN)), and also shows sex differences. These linkages are based on fMRI‐derived slow hemodynamics. Here, we utilized the fine temporal resolution of magnetoencephalography (MEG) to measure resting state functional coupling (FCp) related to individual pain perception and pain interference in 50 healthy individuals (26 women, 24 men). We found that pain sensitivity and pain interference were linked to within‐ and cross‐network broadband FCp across the Asc and SN. We also identified sex differences in these relationships: (a) women exhibited greater within‐network static FCp, whereas men had greater dynamic FCp within the dynamic pain connectome; (b) relationship between pain sensitivity and pain interference with FCp in women was commonly found in theta, whereas in men, these relationships were predominantly in the beta and low gamma bands. These findings indicate that dynamic interactions of brain networks underlying pain involve fast brain communication in men but slower communication in women., We used magnetoencephalography to investigate network‐level brain dynamics that may underlie individual variability in pain behavior and also, sex differences in this system. We found that pain sensitivity and pain interference were related to within‐ and cross‐network static and dynamic functional coupling across nodes of the ascending nociceptive pathway and the salience network and that there were sex differences in these relationships. These results highlight the brain dynamics underlying pain processing that differ between sexes and neural frequency bands.

Background Quantitative magnetic resonance imaging (QMRI) techniques of magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstructural information about the spinal cord. Objective Compare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk herniation (IVDH). Animals Fifty‐one dogs with thoracolumbar IVDH. Methods Prospective cohort study. Quantitative MRI measurements of the spinal cord were obtained at the region of compression. A linear regression generalized estimating equations model was used to compare QMRI measurements between different neurological grades after adjusting for age, weight, duration of clinical signs, and lesion location. Results Grade 5 (.79 × 10−3 mm2/s [median], .43−.91 [range]) and axial (1.47 × 10−3 mm2/s, .58−1.8) diffusivity were lower compared to grades 2 (1.003, .68−1.36; P = .02 and 1.81 × 10−3 mm2/s, 1.36−2.12; P < .001, respectively) and 3 (1.07 × 10−3 mm2/s, .77−1.5; P = .04 and 1.92 × 10−3 mm2/s, 1.83−2.37;P < .001, respectively). Compared to dogs with acute myelopathy, chronic myelopathy was associated with higher mean (1.02 × 10−3 mm2/s, .77−1.36 vs. .83 × 10−3 mm2/s, .64−1.5; P = .03) and radial diffusivity (.75 × 10−3 mm2/s, .38−1.04 vs. .44 × 10−3 mm2/s, .22−1.01; P = .008) and lower MTR (46.76, 31.8−56.43 vs. 54.4, 45.2−62.27; P = .004) and fractional anisotropy (.58, .4−0.75 vs. .7, .46−.85; P = .02). Fractional anisotropy was lower in dogs with a T2‐weighted intramedullary hyperintensity compared to those without (.7, .45−.85 vs. .54, .4−.8; P = .01). Conclusion and Clinical Relevance Mean diffusivity and AD could serve as surrogates of severity of spinal cord injury and are complementary to the clinical exam in dogs with thoracolumbar IVDH.

Background Pain is a subjective experience characterized by sensory (intensity) and emotional (unpleasantness) aspects. Although literature reports behavioural effects on pain due to smell and taste influence, to our knowledge the relationship between tonic pain induced by a capsaicin cream and these chemosensory systems has never been explored before. The aim of this study was to investigate the modulation of olfactory and gustatory substances having different valence on tonic pain perception mediated by a capsaicin cream application. Methods Sixty healthy volunteers were included in two separated experiments (N = 30 smell; N = 30 taste) and underwent different valence smell and taste stimulations, while receiving painful stimuli. Perception of pain intensity (the sensory component) and unpleasantness (the affective component) was measured with a numerical rating scale, both during the two aforementioned experiments. Results Pain unpleasantness rating showed differences only in the smell experiment between the two odourous conditions. In particular, pleasant odour induced lower ratings of pain unpleasantness, while no significant results were found for intensity. Regarding taste, we could not observe significant effects nor for pain unpleasantness or intensity. Conclusions These findings highlight the potential role of pleasant odours in influencing the affective aspects of pain perception induced by this kind of tonic pain. Such evidence might provide new insight for using chemosensory substances as analgesics for modulating the cognitive aspects of neuropathic pain. Significance This work shows the effect of smell on the emotional component of tonic pain, experimentally induced by capsaicin cream application. Previous literature investigated tonic pain in interaction with smell and/or taste stimuli, but mainly with physical methods such as temperature. Our findings add new information in this field, contributing to a deeper insight on the role of olfaction on this particular kind of tonic pain perception. This approach could open to new investigations aimed to consider odours for pain management.

Background: Burning mouth syndrome (BMS) is a chronic pain disorder affecting the oral cavity. Previous work has shown promising analgesic results of bodily illusions in other chronic pain conditions. The aim of this proof‐of‐concept, pilot study was to investigate whether bodily illusions reduce pain in BMS patients. Methods: Nine participants diagnosed with BMS underwent bodily illusions using a MIRAGE‐mediated reality system. All participants completed 4 conditions and performed standardised movements of the tongue. First, a baseline condition was performed while the tongue was viewed at normal size and colour. Then, three conditions were performed in random order: resizing shrink, colour‐based (blue tongue), and incongruent movement illusions. During each condition, participants rated overall pain intensity as well as the intensity of burning pain/sensation on the tongue. Results: There was no difference in overall pain intensity ratings between conditions. However, a significant effect of condition was found for burning pain/sensation of the tongue. The colour illusion significantly reduced burning pain compared with baseline (MD = ‐12.8, 95% CI ‐20.7 to ‐4.8), corresponding to an average pain reduction of 32%. Exploratory analyses showed the colour illusion also significantly reduced pain compared with the shrink illusion (MD = ‐11.7, 95% CI ‐22.2 to ‐1.1). Conclusion: Using visual illusions to change tongue colour to blue resulted in significant reductions in burning pain/sensations in BMS patients for the duration of the illusion. This proof‐of‐concept study suggests that BMS patients may benefit from bodily illusions, and supports additional research using larger samples and more comprehensive control conditions. Refereed/Peer-reviewed

Background Exercise, a cornerstone in current treatments for people with musculoskeletal pain, elicits a phenomenon called exercise‐induced hypoalgesia (EIH), which may result in reduced pain intensity and/or increased pain thresholds. However, EIH can be impaired in patients with musculoskeletal pain, and psychosocial factors may play a mediating role in EIH. Objective The aim of this study was to systematically review the scientific literature regarding the association between psychosocial factors and EIH in healthy people and people with musculoskeletal pain. Methods An extensive search in databases including Medline Ovid, Embase, Web of Science, PsycINFO Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost was carried out. Two reviewers independently carried out study selection, data extraction, and critical appraisal. Included studies analyzed the association or effect of psychosocial factors on EIH in adults with or without musculoskeletal pain. Results Nine cross‐sectional studies were included, 6 involving healthy people and 4 involving people with musculoskeletal pain; 1 study included both. Overall risk of bias was high. Different types of exercise bouts, psychosocial factors, and/or outcome measures were used across studies. In healthy people and people with musculoskeletal pain, most studies did not find an association between psychosocial factors and EIH. However, 1 study involving musculoskeletal pain and 2 studies with healthy people did find a significant association. Conclusion Due to poor quality and heterogeneity between studies, no conclusions can be drawn regarding whether psychosocial factors are associated with EIH or not. This review includes recommendations and directions for further research to investigate the role of psychosocial factors on EIH.

BACKGROUND Local anesthetic is one of the major ways to obtain satisfactory anesthesia in majority of plastic surgical procedures. OBJECTIVES To compare the effect on pain while injecting buffered vs nonbuffered local anesthetic. MATERIALS AND METHODS The single-blind, split-scalp study was conducted in 25 patients undergoing first hair transplant surgery after informed consent and ethics committee approval using two solutions. Solution A was composed of normal saline (200 mL), 2% lidocaine (40 mL), 1 mL of epinephrine 1:1000, and triamcinolone acetate (40 mg). Solution B was composed of normal saline (200 mL), 2% lidocaine (40 mL), 1 mL of epinephrine 1:1000, triamcinolone acetate (40 mg), and 8.4% soda bicarbonate (5 mL). A 3-mL syringe with 30-G needle was used. On one side of the scalp, solution A was used and solution B on the other side. The pain response was recorded using Wong-Baker Faces Pain Scale corresponding to 0-10 scale. The data were analyzed statistically. No preoperative analgesic was used in any patient. The injections were administered by the 2nd author. RESULTS A total of 25 patients were included in the study. The mean age of the patients was 33.4 years (range; 28 to 41 years). The average pain score was 4.96 (range, 3-7) with solution A whereas 3.28 (range, 2-6) using the solution B (P < .05). Eleven of the patients (44%) were smokers. The average pain score in smokers was 5.82 with solution A and 3.73 with solution B. The pain score in nonsmokers was 4.29 with solution A and 2.93 with solution B (P < .05).

Background The association between fear of pain (FOP) and pain intensity has remained unclear. This study aimed to examine whether highly pain-fearful participants showed pain perceptual biases to general painful stimulus or to specific threatening painful stimulus. Methods Fifty-nine undergraduates were recruited into low (n = 30) and high (n = 29) FOP groups and completed a threatening pain perception task with two tasks. Task 1 assessed pain perceptual biases by calculating the percentage of near-threshold pain stimulus judged as painful and assessing the average pain intensity ratings to those painful stimuli. Task 2 assessed pain perceptual biases by measuring pain ratings to each single threshold (low intensity) and twice-threshold (high intensity) pain stimulus. Results Results from task 1 indicated that higher FOP levels were associated with higher pain sensitivity when pain was appraised as a threat, reflected as high FOP group reporting higher pain intensity to those stimuli judged as painful in high threat condition than in low threat condition. Consistently, results from task 2 observed that when noxious stimulus intensity increased to threshold pain and twice threshold pain levels, high FOP group also generally reported higher pain intensity in high threat condition than in low threat condition. However, for both tasks, no such threat level differences were observed in low FOP group. Conclusions The current research emphasized that participants with higher FOP level showed pain perceptual biases to specific threatening painful stimulus. Threat appraisal of pain played a key role in the positive association between pain-related fear and pain perceptual biases. Significance The findings highlight the modulatory influence of threat appraisal of pain in the positive association between pain-related fear and pain perceptual biases.

Pain is experienced by people with cancer during treatment and in survivorship. Exercise can have an acute hypoalgesic effect (exercise‐induced hypoalgesia; EIH) in healthy individuals and some chronic pain states. However, EIH, and the moderating effect of exercise intensity, has not been investigated in cancer survivors. This study examined the effect of low‐ and high‐intensity aerobic exercise on EIH in cancer survivors after a single exercise session as well as a brief period of exercise training (2‐weeks, three exercise sessions per week). Participants (N = 19) were randomized to low‐ (30%–40% Heart Rate Reserve (HRR) or high‐ (60%–70% HRR) intensity stationary cycling for 15–20 min. Pressure pain thresholds (PPT) were assessed over the rectus femoris and biceps brachii before and after a single exercise session and again after a short training period at the assigned intensity. Then, following a 6‐week washout period, the intervention was repeated at the other intensity. After the first exercise session, high‐intensity exercise resulted in greater EIH over the rectus femoris than low intensity (mean difference ± SE: −0.51 kg/cm2 ± 0.15, Cohen's d = 0.78, p = 0.004). After a 2‐week training period, we found no difference in EIH between intensities (0.01 kg/cm2 ± 0.25, d = 0.00 p = 0.99), with comparable moderate effect sizes for both low‐ and high‐intensity exercise, indicative of EIH. No EIH was observed over the biceps brachii of the arm at either low or high intensity. Low‐intensity exercise training may be a feasible option to increase pain thresholds in cancer survivors., High‐intensity exercise increased pressure pain thresholds more than low‐intensity exercise over the exercising muscle of the leg. However, after a short training period, there was no difference between low‐ and high‐intensity exercise on pain thresholds, with both intensities eliciting a hypoalgesic effect. These results suggest that both low‐ and high‐intensity exercise training may be effective at increasing pain thresholds in cancer survivors.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses.METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition.KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing.CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Neuropathic pain is associated with an increased sensitivity to painful stimuli or abnormal sensitivity to otherwise innocuous stimuli. However, in addition to adverse effects, currently available drugs have shown limited response in patients with neuropathic pain, which provides a rationale to explore new drug classes acting on novel targets and with better efficacy and safety profiles. Here, we found that saikosaponins potently inhibit agonist-induced activation of the transient receptor potential A1 (TRPA1) channel, which has been reported to mediate neuropathic pain by sensing a variety of chemical irritants. Molecular docking and site-directed mutagenesis analyses suggested that saikosaponins bind to the hydrophobic pocket in TRPA1 near the Asn855 residue, which, when mutated to Ser, was previously associated with enhanced pain perception in humans. In support of these findings, saikosaponin D significantly attenuated agonist-induced nociceptive responses and vincristine-induced mechanical hypersensitivity in mice. These results indicate that saikosaponins are TRPA1 antagonists and provide a basis for further elaboration of saikosaponin derivatives for the development of new therapeutics for neuropathic pain.

This systematic review and meta-analysis analysed whether pain and disruptive behaviour can be decreased by the use of computerized local dental anaesthesia (CDLA) in children. The literature was screened to select randomized clinical trials that compared computerized and conventional anaesthesia. The primary outcome was pain perception during anaesthesia; the secondary, disruptive behaviour. The risk of bias of individual papers and the quality of the evidence were evaluated. After search, 8389 records were found and 20 studies remained for the qualitative and quantitative syntheses. High heterogeneity was detected for both outcomes. For the pain perception, the overall analysis showed a standard mean difference of -0.78 (-1.31, -0.25) favouring CDLA; however, when only studies at low risk of bias were analysed (subgroup analysis), there was no difference between the two techniques [-0.12(-0.46, 0.22)]. For disruptive behaviour, no differences were detected for continuous [-0.26 (-0.68, 0.16)] or dichotomous data [0.81 (0.62, 1.06)]. The quality of evidence was judged as low for pain perception and very low for disruptive behaviour. It is concluded that there is no difference in the pain perception and disruptive behaviour in children subjected to computerized or conventional dental local anaesthesia. Notwithstanding, the quality of the available evidence is low.

Positive and negative expectancies drive behavioral and neurobiological placebo and nocebo effects, which in turn can have profound effects on patient improvement or worsening. However, expectations of events and outcomes are often not met in daily life and clinical practice. It is currently unknown how this affects placebo and nocebo effects. We have demonstrated that the violation of expectancies, such as when there is a discrepancy between what is expected and what is actually presented, reduces both placebo and nocebo effects while causing an extinction of placebo effects. The reduction of placebo and nocebo effects was paralleled by an activation of the left inferior parietal cortex, a brain region that redirects attention when discrepancies between sensory and cognitive events occur. Our findings highlight the importance of expectancy violation in shaping placebo and nocebo effects and open up new avenues for managing positive and negative expectations in clinical trials and practices.

Background Three TRPV1 (Transient Receptor Potential Vanilloid Receptor 1) antagonists were developed for testing in situ in human skin (Sjogren et al., 2016; Sjogren et al., 2018; Sjogren et al., 2018). The first human study using these compounds and capsaicin, was performed to determine the required local antagonist concentrations needed for target engagement (Proof of Mechanism, PoM) (Sjogren et al., 2018). In this paper, the aim was to address a TRPV1 antagonist's ability to inhibit a more complex pain signal and to define translational endpoints that could be used in further drug development, when progressing orally bioavailable TRPV1 antagonists as novel analgesic medications. Method This was a single centre, placebo-controlled, clinical proof of principle (PoP) study in 25 healthy volunteers. The subjects were exposed to UV irradiation, causing a local tissue inflammation. Three different doses of AZ12048189 were administered to assess pain perception through quantitative sensory testing (QST) and erythema using Laser Doppler scanning. Results AZ12048189 increased the warmth detection threshold (WDT) and the heat pain threshold (HPT) and decreased the intensity of supra threshold heat pain (STHP). AZ12048189 did not, however, have any significant effects as assessed using mechanical stimulation or Laser Doppler. Conclusions This study validated translational tools to confirm target engagement for TRPV1 antagonists; WDT, HPT and STHP have utility in this respect, after oral administration of a TRPV1 antagonist. This study also proved that TRPV1 antagonists can inhibit a more complex, non-capsaicin dependent thermally induced pain signal.

BACKGROUND In this eye tracking study, we evaluated pain-related biases in orienting and maintenance of gaze within impending touch versus impending pain tasks and examined features of pain resilience as individual difference influences on potential biases. METHODS Gaze preferences of healthy adults (25 women and 39 men) were assessed during standardized pain-neutral (P-N) image pair presentations (2,000 ms) of an impending touch task versus an impending pain task whereby image pair offsets were followed by potential non-painful touch and potential pain stimulation, respectively. RESULTS Within each task, participants were significantly more likely to fixate first upon pain images in P-N pairs and maintain gaze on these images for longer overall durations during trials. Between task comparisons indicated pain-related biases in orienting and maintenance were significantly stronger when image pairs signalled potential pain rather than impending touch. Finally, within the impending pain task, higher scores on the behaviour perseverance dimension of pain resilience were related to shorter first fixation durations and overall gaze durations towards pain images. CONCLUSIONS Supporting specific threat interpretation model premises, comparatively more threatening external pain cues for impending pain were characterized by gaze biases reflecting pronounced early attentional capture and subsequent prolonged vigilance. However, elevations in self-reported behavioural perseverance in spite of pain corresponded to an increased capacity to disengage from pain images that signalled potential pain. SIGNIFICANCE Gaze biases were assessed within a comparatively benign "impending touch" paradigm versus a higher threat, impending pain task. Early capture and maintenance of gaze towards pain images were more pronounced on the latter task, although pain resilient participants were able to disengage more easily from pain images signalling possible pain.

BACKGROUND Cutting is the most common method of non-suicidal self-injury (NSSI) to reduce inner tension in patients with Borderline Personality Disorder (BPD). Aim of this study was to compare pain perception induced by an incision and by application of a surrogate model for sharp mechanical pain (a non-invasive "blade") in BPD. METHODS 22 female patients and 20 healthy controls (HC) received a small incision into the volar forearm, a 7s-blade application on the same side, and non-invasive phasic stimuli (pinprick, blade, laser, tactile). Pain intensity as well as affective versus sensory components were assessed. RESULTS Incision was rated similarly by both groups (BPD: 28.6 ± 5.5 vs. HC: 33.9 ± 6.6; mean maximum pain ± SEM; p > 0.8), without significant difference for "7-s-blade" (BPD: 18.1 ± 3.8 vs. HC: 25.3 ± 3.6; mean maximum pain ± SEM; p > 0.17) or between "7-s-blade" and incision (BPD: p > 0.12; HC: p > 0.84). However, patients' intensity ratings returned significantly faster to baseline after incision (BPD: 38.9 ± 12.6 s vs. HC: 74.52 ± 11.5 s; p

BACKGROUND AND AIMS Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS. METHODS Forty-five BMS patients (43 women), mean age 62.5 years, and 32 healthy controls (30 women), mean age 64.8 years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed. RESULTS Cool (p = 0.0090) and warm detection thresholds (p = 0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p = 0.0056). The latencies of R2 component were longer in BMS patients than in controls (p = 0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p = 0.0312) in homozygous patients with 957TT, who also reported most interference (p = 0.0352) and greatest suffering (p = 0.0341). Genotype 957CC associated with sleep disturbances (p = 0.0254). CONCLUSIONS Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain. SIGNIFICANCE The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

Objectives: To determine the level of agreement among patients with rheumatoid arthritis (RA) with the principles and recommendations of the treat-to-target (T2T) initiative in New Zealand (NZ) and to further explore specific patient opinions via online iterative surveys. Methods: Participants with RA were recruited from rheumatology clinics in NZ and invited to receive and reply to surveys administered via the Patient Opinion Real-Time Anonymous Liaison (PORTAL) system. An enrolment survey recorded demographics, disease duration and treatment and then RA T2T surveys were administered weekly. A Likert scale 1-5 measured agreement with the principles and recommendations and further surveys explored responses of interest identified by investigators from each prior survey. Results: One hundred and ninety patients consented to participate in PORTAL and 132 in the RA T2T surveys. Level of agreement with RA T2T principles was: 93.3% to 99.3% and to the recommendations: 77.3%-100%. The lowest level of agreement 77.3% was with recommendation 8, 3 monthly treatment adjustment, and the highest was 100% agreement with recommendation 10, shared decision-making. Patients agreed less with low disease activity as the target compared with remission (91.4% and 98%). Despite high-level agreement for the use of a disease activity score (95.7%), 23% did not feel the individual components reflected their disease control. Patients rated difficulty coping, erosions on imaging, health-related quality of life and pain all significantly higher than C-reactive protein as indicators of worsening arthritis. Conclusions: Despite a high level of patient agreement with RA T2T this study highlights the importance of patient engagement in the RA T2T process to individualize therapy adjustments, make shared decisions and decide on targets that accurately reflect disease control according to patients.

Following injury to the peripheral nervous system (PNS), microglia in the spinal dorsal horn (SDH) become activated and contribute to the development of local neuro-inflammation, which may regulate neuropathic pain processing. The molecular mechanisms that control microglial activation and its effects on neuropathic pain remain incompletely understood. We deleted the gene encoding the plasma membrane receptor, LDL Receptor-related Protein-1 (LRP1), conditionally in microglia using two distinct promoter-Cre recombinase systems in mice. LRP1 deletion in microglia blocked development of tactile allodynia, a neuropathic pain-related behavior, after partial sciatic nerve ligation (PNL). LRP1 deletion also substantially attenuated microglial activation and pro-inflammatory cytokine expression in the SDH following PNL. Because LRP1 shedding from microglial plasma membranes generates a highly pro-inflammatory soluble product, we demonstrated that factors which activate spinal cord microglia, including lipopolysaccharide (LPS) and colony-stimulating factor-1, promote LRP1 shedding. Proteinases known to mediate LRP1 shedding, including ADAM10 and ADAM17, were expressed at increased levels in the SDH after PNL. Furthermore, LRP1-deficient microglia in cell culture expressed significantly decreased levels of interleukin-1β and interleukin-6 when treated with LPS. We conclude that in the SDH, microglial LRP1 plays an important role in establishing and/or amplifying local neuro-inflammation and neuropathic pain following PNS injury. The responsible mechanism most likely involves proteolytic release of LRP1 from the plasma membrane to generate a soluble product that functions similarly to pro-inflammatory cytokines in mediating crosstalk between cells in the SDH and in regulating neuropathic pain.

AIM AND OBJECTIVE To provide evidence regarding the psychometric properties of the Spanish eight-item version of the Chronic Pain Acceptance Questionnaire (CPAQ-8). METHOD Three hundred adults with chronic pain completed measures of pain acceptance, committed action, fear of movement, anxiety, depression, and health-related quality of life. A confirmatory factor analysis (CFA) of the CPAQ-8 was performed. Reliability and validity were also evaluated. RESULTS The CFA confirmed a two-factor structure. The CPAQ-8 Total and subscale scores showed acceptable-to-good internal consistency. Furthermore, the Total and the Activity Engagement scale scores showed moderate associations with Committed Action scores, supporting construct validity. Both the Total and the two subscale scores showed good criterion validity. CONCLUSION The findings provide further support for the reliability and validity of the Spanish version of the CPAQ-8 Total and subscale scores.

Background and Aim Emerging evidence indicates that psychological stress is involved in the pathogenesis of irritable bowel syndrome, which is characterized by visceral hypersensitivity and may be accompanied by gut dysbiosis. However, how such stress contributes to the development of visceral hypersensitivity is incompletely understood. Here, we aimed to investigate the influence that stress‐induced microbial changes exert on visceral sensitivity, as well as the possible underlying mechanisms associated with this effect. Methods Male Sprague–Dawley rats underwent chronic water avoidance stress (WAS) to induce visceral hypersensitivity. Visceral sensitivity, colonic tight junction protein expression, and short‐chain fatty acids of cecal contents were measured. Fecal samples were collected to characterize microbiota profiles. In a separate study, oral gavage of Roseburia in WAS rats was conducted to verify its potential role in the effectiveness on visceral hypersensitivity. Results Repeated WAS caused visceral hypersensitivity, altered fecal microbiota composition and function, and decreased occludin expression in the colon. Stressed rats exhibited reduced representation of pathways involved in the metabolism of butyrate and reduced abundance of several operational taxonomic units associated with butyrate‐producing bacteria, such as Lachnospiraceae. Consistently, supplementation with Roseburia hominis, a species belonging to Lachnospiraceae, significantly increased cecal butyrate content. Moreover, Roseburia supplementation alleviated visceral hypersensitivity and prevented the decreased expression of occludin. Conclusions Reduction in the abundance of butyrate‐producing Lachnospiraceae, which is beneficial for the intestinal barrier, was involved in the formation of visceral hypersensitivity. R. hominis is a potential probiotic for treating stress‐induced visceral hypersensitivity.

Background Spinal cord injury (SCI) causes continuous neurological deficits and major sensory-motor impairments. There is no effective treatment to enhance sensory-motor function following SCI. Thus, it is crucial to develop novel therapeutics for this particular patient population. Astaxanthin (AST) is a strong antioxidant, anti-inflammatory and anti-apoptotic agent. In the present study, it was tested in a severe compression SCI model with emphasis on sensory-motor outcomes, signalling pathway, along with other complications. Methods A severe SCI was induced by compression of the rat thoracic spinal cord with an aneurysm clip and treatment with AST or the vehicle was carried out, 30 min after injury. Behavioural tests including open field, von Frey, hot plate and BBB were performed weekly to 28 days post-injury. Rats were assigned to measure blood glucose, weight and auricle temperature. Western blot and histological analysis also were performed at the same time points. Results AST decreased mechanical and thermal pain and also improved motor function performance, reduced blood glucose and auricle temperature increases and attenuated weight loss in SCI rats. Western blot analysis showed decreased activation of ERK1/2 and increased activation of AKT following AST treatment. The histology results revealed that AST considerably preserved myelinated white matter and the number of motor neurons following SCI. Conclusion Taken together, the beneficial effects of AST to improve sensory-motor outcomes, attenuate pathological tissue damage and modulate ERK and AKT signalling pathways following SCI, suggest it as a strong therapeutic agent towards clinical applications. Significance Spinal cord injury (SCI) impairs sensory-motor function and causes complications, which astaxanthin (AST) has the potential to be used as a treatment for. The present study investigates the effects of AST in a compression model of SCI with emphasis on sensory-motor outcomes alongside other complications, histopathological damage and also related signalling pathways.