Sunday, December 27, 2020

Analgesic effect of music during wound care among patients with diaphyseal tibial fractures: Randomized controlled trial

Abstract

Background

Evidence is scarce regarding the analgesic effect of music for the relief of acute pain during the care of surgical tibial fracture wounds.

Objective

To evaluate the analgesic effect of music on acute procedural pain during the care of surgical tibial fracture wounds.

Method

This was a randomized, controlled, blinded clinical trial with 70 patients in the immediate postoperative period for diaphyseal tibial fracture surgery. Participants were randomly allocated to two groups: a control group (CG), in which patients received only the institution's standard analgesia, and an intervention group (IG) composed of patients receiving a 30‐min session of music of their own choice, as a complementary method to the institution's standard analgesia. Pain was evaluated during the first postoperative dressing change, using the Numerical Rating Scale (NRS).

Results

The sample was homogeneously composed of men (91.4%), young adults (61.4%), without previous diseases (88.6%) and whose traumas were related to a motorcycle crash (84.3%). The main musical genres chosen by participants were the most popular in their region (61.4%). Those who listened to music presented lower pain scores when compared with those in the CG (IG:2.4 ± 2.4 versus CG:5.8 ± 2.7; p < 0.001; η2 = 0.171; p < 0.001).

Conclusion

Listening to music is effective for relieving acute procedural pain during the first post‐operative tibial fracture dressing change. Music should be incorporated into the multimodal analgesia protocols for management of orthopedic postoperative wound care‐related pain.

Significance

Patients with diaphyseal tibial fractures that listened to music before and during the wound dressing change showed less pain when compared to those who received the standardized pharmacologic analgesia alone.



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Wednesday, December 23, 2020

Nociceptive nerves regulate haematopoietic stem cell mobilization

Nature, Published online: 23 December 2020; doi:10.1038/s41586-020-03057-y

Stimulation of pain-sensing neurons, which can be achieved in mice by the ingestion of capsaicin, promotes the migration of haematopoietic stem cells from the bone marrow into the blood.

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Pain-sensing neurons mobilize blood stem cells from bone marrow

Nature, Published online: 23 December 2020; doi:10.1038/d41586-020-03577-7

Pain-sensing nerve cells can mobilize blood stem cells in mice, with a component of chilli peppers being one stimulus. The finding holds the promise of improving procedures for stem-cell transplantation.

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Tuesday, December 22, 2020

Activation of the regeneration‐associated gene STAT3 and functional changes in intact nociceptors after peripheral nerve damage in mice

Abstract

Background

In the context of neuropathic pain, the contribution of regeneration to the development of positive symptoms is not completely understood. Several efforts have been done to described changes in axotomized neurons, however, there is scarce data on changes occurring in intact neurons, despite experimental evidence of functional changes. To address this issue, we analyzed by immunohistochemistry the presence of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), an accepted marker of regeneration, within DRGs where axotomized neurons were retrogradely labeled following peripheral nerve injury. Likewise, we have characterized abnormal electrophysiological properties in intact fibers after partial nerve injury.

Methods/Results

We showed that induction of pSTAT3 in sensory neurons was similar after partial or total transection of the sciatic nerve and to the same extent within axotomized and non‐axotomized neurons. We also examined pSTAT3 presence on non‐peptidergic and peptidergic nociceptors. Whereas the percentage of neurons marked by IB4 decrease after injury, the proportion of CGRP neurons did not change, but its expression switched from small‐ to large‐diameter neurons. Besides, the percentage of CGRP+ neurons expressing pSTAT3 increased significantly 2.5‐folds after axotomy, preferentially in neurons with large diameters. Electrophysiological recordings showed that after nerve damage, most of the neurons with ectopic spontaneous activity (39/46) were non‐axotomized C‐fibers with functional receptive fields in the skin far beyond the site of damage.

Conclusions

Neuronal regeneration after nerve injury, likely triggered from the site of injury, may explain the abnormal functional properties gained by intact neurons, reinforcing their role in neuropathic pain.



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Sunday, December 20, 2020

Intra‐accumbal dopaminergic system modulates the restraint stress‐induced antinociceptive behaviors in persistent inflammatory pain

Abstract

Background

Stress activates several neural pathways that inhibit pain sensation. Nucleus accumbens (NAc) as an important component of the mesolimbic dopaminergic system, has a major role in pain modulation and is differentially affected by stress. Based on the nature of stressors, the direction of this effect is controversial. We previously showed that forced swim stress‐induced analgesia through activation of NAc dopamine receptors. In this study, we aimed to examine the role of dopamine receptors within the NAc in restraint stress (RS) induced analgesia.

Methods

Male Wistar rats weighing 230–250 g were unilaterally implanted with a cannula into the NAc. D1‐like dopamine receptor antagonist, SCH‐23390 (0.25, 1 and 4µg/0.5µl saline) or D2‐like dopamine receptor antagonist, Sulpiride (0.25, 1 and 4µg/0.5µl DMSO) were microinjected into NAc in two separate super groups 5 min prior to exposure to RS. Their control groups just received intra‐accumbal saline or DMSO (0.5 µl), respectively. The formalin test was performed after animals were subjected to RS using Plexiglas tubes.

Results

The results demonstrated that RS produces analgesia in both phases of the formalin test. Intra‐NAc injection of SCH‐23390 equally reduced RS induced analgesia in both early and late phases of the formalin test, while Sulpiride reduced RS induced analgesia just at the late phase.

Conclusions

These findings suggest that the dopaminergic system might act as a potential endogenous pain control system in stress conditions. However, the lack of evaluation of the role of the dopaminergic system in RS‐induced antinociception in acute pain conditions is considered as a limitation for this study. In addition, a comprehensive evaluation of this endogenous pain control system in animal and clinical studies will guide future efforts for developing more effective medication.



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Social Support, Social Cohesion and Pain during Pregnancy: The Japan Environment and Children’s Study

Abstract

Background

Persistent pain during pregnancy is a significant health issue, which could be correlated with psychological distress resulting from inadequate social support. This study aims to investigate whether the relationship between poor social support and antenatal pain is mediated by psychological distress. We also aimed to examine whether social cohesion moderates the influence of psychological distress on the relationship between social support and antenatal pain.

Methods

We analyzed 94,517 pregnancies of women from a Japanese national birth cohort completed questionnaires assessing pain, social support, social cohesion, and psychological distress. Psychological distress was assessed using the Kessler Psychological Distress Scale. Two types of models were used: the mediation model to examine whether the association between social support and pain was mediated by psychological distress; the moderated mediation model to analyze whether social cohesion buffered the negative effect of inadequate social support on pain. Demographic, socioeconomic, psychological, factors were controlled for in all analyses.

Results

The association between social support and pain mediated by psychological distress was 75.8%. Social cohesion had a focal moderation effect on the inverse association between social support and psychological distress (unstandardized regression coefficient [β] = 0.09; 95% CI, 0.07–0.11) and functioned as moderator for the indirect effect of social support on antenatal pain (index of moderated mediation = 0.006; 95% CI, 0.004–0.007).

Conclusions

Poor social support was related to antenatal pain through psychological distress, possibly buffered by social cohesion. During the antenatal period, social support and cohesion are important for women.



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Saturday, December 19, 2020

Six‐year trends in postoperative prescribing and use of multimodal analgesics following total hip and knee arthroplasty: A single‐site observational study of pain management

Abstract

Background

Guidelines for acute postoperative pain management recommend administering analgesics in multimodal combination to facilitate synergistic benefit, reduce opioid requirements and decrease side‐effects. However, limited observational research has examined the extent to which multimodal analgesics are prescribed and administered postoperatively following joint replacement.

Methods

In this longitudinal study, we used three‐point prevalence surveys to observe the 6‐year trends in prescribing and use of multimodal analgesics on the orthopaedic wards of a single Australian private hospital. We collected baseline postoperative data from total hip and knee arthroplasty patients in May/June 2010 (Time 1, n = 86), and follow‐up data at 1 year (Time 2, n = 199) and 5 years (Time 3, n = 188). During the follow‐up, data on prescribing practices were presented to anaesthetists.

Results

We found a statistically significant increase in the prescribing (p < 0.001) and use (p < 0.001) of multimodal analgesics over time. The use of multimodal analgesics was associated with lower rest pain (p = 0.027) and clinically significant reduction in interference with activities (p < 0.001) and sleep (p < 0.001). However, dynamic pain was high and rescue opioids were likely under‐administered at all time points. Furthermore, while patients reported high levels of side‐effects, use of adjuvant medications was low.

Conclusions

We observed significant practice change in inpatient analgesic prescribing in favour of multimodal analgesia, in keeping with contemporary recommendations. Surveys, however, appeared to identify a clinical gap in the bedside assessment and management of breakthrough pain and medication side‐effects, requiring additional targeted interventions.

Significance

Evaluation of 6‐year trends in a large Australian metropolitan private hospital indicated substantial growth in postoperative multimodal analgesic prescribing. In the context of growing global awareness concerning multimodal analgesia, findings suggested diffusion of best‐evidence prescribing into clinical practice. Findings indicated the effects of postoperative multimodal analgesia in real‐world conditions outside of experimental trials. Postoperative multimodal analgesia in the clinical setting was only associated with a modest reduction in rest pain, but substantially reduced interference from pain on activities and sleep.



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Psoralens activate and photosensitize Transient Receptor Potential channels Ankyrin type 1 (TRPA1) and Vanilloid type 1 (TRPV1)

Abstract

Background

PUVA (psoralen UVA) therapy is used to treat a variety of skin conditions, such as vitiligo psoriasis, eczema and mycosis fungoides, but it is frequently accompanied by phototoxicity leading to burning pain, itch and erythema.

Methods

We used a combination of calcium and reactive oxygen species (ROS) imaging, patch clamp and neuropeptide release measurement to investigate whether certain ion channels involved in pain and itch signalling could be responsible for these adverese effects of PUVA.

Results

Clinically used psoralen derivatives 8‐methoxypsoralen (8‐MOP) and 5‐methoxypsoralen at physiologically relevant concentrations were able to activate and photosensitize two recombinant thermoTRP (temperature‐gated Transient Receptor Potential) ion channels, TRPA1 (Transient Receptor Potential Ankyrin type 1) and TRPV1 (Transient Receptor Potential Vanilloid type 1). 8‐MOP enhanced ROS production by UVA light, and the effect of 8‐MOP on TRPA1 could be abolished by the antioxidant N‐acetyl cysteine and by removal of critical cysteine residues from the N‐terminus domain of the channel. Natively expressed mouse TRPA1 and TRPV1 both contribute to photosensitization of cultured primary afferent neurons by 8‐MOP, while direct neuronal activation by this psoralen‐derivative is mainly dependent on TRPV1. Both TRPA1 and TRPV1 are to a large extent involved in controlling 8‐MOP‐induced neuropeptide release from mouse trachea.

Conclusions

Taken together our results provide a better understanding of the phototoxicity reported by PUVA patients and indicate a possible therapeutic approach to alleviate the adverse effects associated with this therapy.

Significance

Our work provides evidence for the involvement of thermoTRP channels TRPA1 and TRPV1 in the activation and photosensitization of peripheral nociceptors during PUVA (Psoralen UVA) therapy.



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Perceived validation and criticism in pain: Development of a new measure in chronic pain

Abstract

Background

Research suggests that the way others react to a pain flare‐up impacts on psychological and pain‐related symptoms in chronic pain (CP). Experiencing validation from others is associated with less negative emotions and better functioning. Contrarily, experiencing criticism is linked to greater pain intensity and worse functioning. Nonetheless, studies are limited by an exclusive focus on spouses rather than significant other relationships, the use of proxy constructs (e.g. social support, responsiveness, solicitousness) rather than specific measures of validation and criticism and a focus on significant others′ behaviour rather than patients′ subjective experience. This study examines the psychometric properties of a new measure – Perceived Validation and Criticism in Pain Questionnaire (PVCPQ), and tests its contribution to functional impairment beyond pain intensity, sociodemographic and medical‐related variables, positive and negative affect, safeness and compassion from others.

Methods

Women with CP (N = 172), 130 (75.6%) of whom had fibromyalgia, completed an online battery of questionnaires (PVCPQ; numeric pain rating scale; work and social adjustment scale; positive and negative affect schedule; social and pleasure scale; compassionate engagement and action scale). Exploratory factor analysis (EFA), reliability analysis, correlational analysis and hierarchical regression analysis were performed.

Results

EFA showed a 23‐item two‐factor solution with good psychometric properties. Criticism in pain (but not validation in pain) contributed to functional impairment above and beyond the variance explained by pain intensity, sociodemographic and medical variables, positive and negative affect, safeness and compassion from others.

Conclusions

These findings suggest that the PVCPQ is a psychometrically valid new measure of perceived validation and criticism in pain that contributes to explaining pain‐related functional impairment.

Significance

The current study provides a new 23‐item measure of perceived validation and criticism by others in chronic pain that overcomes the limitations of existing measures. It adds to the literature by suggesting that perceived criticism (but not validation) contributes to functional impairment beyond sociodemographic variables, pain intensity, affect and related constructs such as social safeness and compassion from others. These results suggest that psychosocial interventions that aim to promote functioning in chronic pain should focus on the subjective experience of being criticized and validated by significant others.



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The impact of parental contact upon cortical noxious‐related activity in human neonates

Abstract

Background

Neonates display strong behavioural, physiological and cortical responses to tissue‐damaging procedures. Parental contact can successfully regulate general behavioural and physiological reactivity of the infant, but it is not known whether it can influence noxious‐related activity in the brain. Brain activity is highly dependent upon maternal presence in animal models, and therefore this could be an important contextual factor in human infant pain‐related brain activity.

Methods

Global topographic analysis was used to identify the presence and inter‐group differences in noxious‐related activity in three separate parental contexts. EEG was recorded during a clinically required heel lance in three age and sex‐matched groups of neonates (a) while held by a parent in skin‐to‐skin (n = 9), (b) while held by a parent with clothing (n = 9) or (c) not held at all, but in individualized care (n = 9).

Results

The lance elicited a sequence of 4–5 event‐related potentials (ERPs), including the noxious ERP (nERP), which was smallest for infants held skin‐to‐skin and largest for infants held with clothing (p=0.016). The nERP was then followed by additional and divergent long‐latency ERPs (> 750 ms post‐lance), not previously described, in each of the groups, suggesting the engagement of different higher level cortical processes depending on parental contact.

Conclusions

These results show the importance of considering contextual factors in determining infant brain activity and reveal the powerful influence of parental contact upon noxious‐related activity across the developing human brain.

Significance

This observational study found that the way in which the neonatal brain processes a noxious stimulus is altered by the type of contact the infant has with their mother. Specifically, being held in skin‐to‐skin reduces the magnitude of noxious‐related cortical activity. This work has also shown that different neural mechanisms are engaged depending on the mother/infant context, suggesting maternal contact can change how a baby's brain processes a noxious stimulus.



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Prevalence and incidence of phantom limb pain, phantom limb sensations and telescoping in amputees: A systematic rapid review

Abstract

Background and objective

This systematic, rapid review aimed to critically appraise and synthesize the recent literature (2014–2019) evaluating the incidence and prevalence of post‐amputation phantom limb pain (PLP) and sensation (PLS).

Databases and data treatment

Five databases (Medline, Embase, Emcare, PsychInfo, Web of Science) and Google Scholar were searched, with two independent reviewers completing eligibility screening, risk of bias assessment and data extraction.

Results

The search identified 1,350 studies with 12 cross‐sectional and 3 prospective studies included. Studies evaluated traumatic (n = 5), atraumatic (n = 4), and combined traumatic/atraumatic (n = 6) amputee populations, ranging from 1 month to 33 years post‐amputation. Study heterogeneity prevented data pooling. The majority of studies had a high risk of bias, primarily due to limited generalizability. Three studies evaluated PLP incidence, ranging from 2.2% (atraumatic; 1 month) to 41% (combined; 3 months) and 82% (combined; 12 months). Only one study evaluated PLS/telescoping incidence. Across contrasting populations, PLP point prevalence was between 6.7%–88.1%, 1 to 3‐month period prevalence was between 49%‐93.5%, and lifetime prevalence was high at 76%–87%. Point prevalence of PLS was 32.4%‐90%, period prevalence was 65% (1 month) and 56.9% (3 months), and lifetime prevalence was 87%. Telescoping was less prevalent, highest among traumatic amputees (24.6%) within a 1‐month prevalence period. Variations in population type (e.g. amputation characteristics) and incidence and prevalence measures likely influence the large variability seen here.

Conclusions

This review found that lifetime prevalence was the highest, with most individuals experiencing some type of phantom phenomena at some point post‐amputation.

Significance

This systematic rapid review provides a reference for clinicians to make informed prognosis estimates of phantom phenomena for patients undergoing amputation. Results show that most amputees will experience phantom limb pain (PLP) and phantom limb sensations (PLS): high PLP incidence 1‐year post‐amputation (82%); high lifetime prevalence for PLP (76%–87%) and PLS (87%). Approximately 25% of amputees will experience telescoping. Consideration of individual patient characteristics (cause, amputation site, pre‐amputation pain) is pertinent given their likely contribution to incidence/prevalence of phantom phenomena.



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High individual pain variability in people living with HIV: A graphical analysis

Abstract

Background

People living with HIV (PLWH) frequently experience pain. Following calls to analyse individual‐level data in addition to group‐level data in pain studies, we compared individual and group‐level changes in pain prevalence, intensity and number of pain sites over 48 weeks in a large cohort of PLWH. This is the largest ever cohort study of pain in PLWH, and is the first to report pain at the level of the individual.

Methods

Participants included all participants with complete pain records from a randomized clinical trial (RCT) for the treatment of HIV (n = 787/1053). At weeks 0, 12, 24, 36 and 48 we assessed participants’ pain in the last week; presence of pain, and if present, the intensity and locations of the pain. We used standard averaging methods to describe data at the group level, and unique graphical reporting methods to analyse data at the level of the individual.

Results

Group‐level data demonstrated a trend for pain prevalence to decline over time (19% week 0, 12% week 48). Worst pain intensity remained stable (median between 4/10 and 5/10), as did the number (median = 1) and common sites of pain across the 48 weeks. In contrast, individual‐level data demonstrated high intra‐individual variability with regards to the presence of pain, and the intensity and location of the pain.

Conclusions

While our group‐level data were similar to previous longitudinal studies, an apparent reduction in pain over 48 weeks, the individual‐level data showed large variability within individuals in that same time frame.

Significance

This graphical analysis highlights the high variability in pain (pain prevalence, intensity and body sites) across time in people living with HIV, and how presenting averaged data hides this important variability. Our data support the reporting of individual‐level data in human experimental and observational studies.



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The effect of in‐session exposure in Fear‐Avoidance treatment of chronic low back pain: A randomized controlled trial

Abstract

Background

Treatment based on the Fear‐Avoidance (FA) model has been found to be effective with chronic low back pain (CLBP), and in‐vivo exposure of fear evoking movements is proposed as a key change mechanism. Exposure tasks may be conducted in the session (in‐session exposure; ISE), in other real‐life situations (between sessions exposure) as part of homework assignments, or both. Utilising a randomized, controlled dismantling study design, the aim of this study was to examine the unique effects of ISE in FA‐treatment of CLBP.

Methods

Patients (N = 90) with CLBP as primary medical complaints were randomized to receive six sessions of either (a) FA‐treatment with ISE (FA‐ISE) or (b) FA‐treatment without ISE (FA), allowing for between sessions exposure in both treatment groups. Patients were assessed with a large battery of outcome measures at four time‐points (pre‐treatment, post‐treatment, after a booster‐session and at 1‐year follow‐up) including pain intensity, pain catastrophising, self‐efficacy, physical performance and quality of life.

Results

Both treatment groups (FA‐ISE, FA) demonstrated statistically significant improvements on primary and most secondary outcomes, with mostly non‐significant between‐group differences.

Conclusions

No added benefit was found for the inclusion of ISE of feared movements in FA‐treatment for CLBP, delivered in a group format to participants with moderately elevated levels of fear‐avoidance beliefs. Clinical trials: NCT01158339.

Significance

This study adds to the existing research literature demonstrating FA‐treatment to be effective with CLBP, but further experimental studies are needed in order to examine under what circumstances ISE of feared movements may add to positive treatment outcomes.



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Preventing pain after breast surgery: A systematic review with meta‐analyses and trial‐sequential analyses

Abstract

Background and objective

The aim of this systematic review was to indirectly compare the efficacy of any intervention, administered perioperatively, on acute and persistent pain after breast surgery.

Databases and data treatment

We searched for randomized trials comparing analgesic interventions with placebo or no treatment in patients undergoing breast surgery under general anaesthesia. Primary outcome was intensity of acute pain (up to 6 hr postoperatively). Secondary outcomes were cumulative 24‐hr morphine consumption, incidence of postoperative nausea and vomiting (PONV), and chronic pain. We used an original three‐step approach. First, meta‐analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE.

Results

Seventy‐three trials (5,512 patients) tested loco‐regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, N‐methyl‐D‐aspartate antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (visual analogue scale > 1.0 cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24‐hr morphine consumption (> 30%). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available.

Conclusions

Mainly with loco‐regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption and PONV incidence after breast surgery. For rational decision making, data on chronic pain are needed.

Significance

This quantitative systematic review compares eight interventions, published across 73 trials, to prevent pain after breast surgery, and grades their degree of efficacy. The most efficient interventions are paravertebral blocks, pectoralis blocks and glucocorticoids, with moderate to low evidence for the blocks. Intravenous lidocaine and alpha2 agonists are efficacious to a lesser extent, but with a higher level of evidence. Data for chronic pain are lacking.



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Issue Information

European Journal of Pain, Volume 25, Issue 1, Page 1-2, January 2021.

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Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel‐associated acute pain syndrome in mice

Abstract

Background

Paclitaxel (PCX) is the first‐line choice for the treatment of several types of cancer, including breast, ovarian, and lung cancers. However, patients who receive even a single dose with PCX commonly develop mechanical and cold allodynia, a symptom known as PCX‐associated acute pain syndrome (P‐APS). Here, we assessed possible involvement of kinin–kallikrein and renin‐angiotensin systems in P‐APS in mice.

Methods

Male mice C57Bl/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1−/−) and B2 (B2−/−), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P‐APS was induced by administration of PCX 4 mg/kg, i.v.. ACE inhibitors (captopril and enalapril), antagonists for angiotensin II type 1 (losartan) and type 2 ([AT2R]; PD123319 and EMA 401) receptors were administrated prior the treatment with PCX. RT‐PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors.

Results

Administration of PCX in B1−/− and B2−/− mice induced lower mechanical and cold allodynia compared to the WT. However, the pre‐treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P‐APS. Surprisingly, we found that mice pre‐treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX.

Conclusion

Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P‐APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P‐APS in humans.

Significance

Kinin–kallikrein and renin‐angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel‐associated acute pain syndrome (P‐APS) in mice. Antagonists for AT2R are potential alternatives to prevent P‐APS.



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Factors associated with physician consultation and medication use in children and adolescents with chronic pain: A scoping review and original data

Abstract

Background

Although paediatric chronic pain is common, it is not yet clear which individuals with chronic pain are likely to seek health care for their pain. The aims of this study were to summarize the current evidence of the characteristics of children and adolescents with chronic pain who consult a physician or use medication for their pain. Additionally, we aimed to expand knowledge by further investigating key and promising, factors in a large community sample of adolescents.

Methods

First, using scoping review methodology, studies on health care utilisation in paediatric chronic pain were identified by the systematic literature search. Out of 1,158 articles, 12 were included for data extraction. Second, in a population‐based cross‐sectional survey, data of N = 2,280 adolescents (10–18 years) and their parents (N = 1,464), were analysed. Univariable logistic and multivariable LASSO regression models were calculated for adolescents with chronic pain (n = 749) to identify predictors of physician visits or analgesics intake due to pain, controlling for acute illness and injury.

Results

The scoping review identified higher pain intensity, frequency, severity and pain‐related disability as significant individual factors associated with physician consultation. Female sex and higher pain intensity were associated with medication consumption. Multivariable analyses with cross‐sectional data revealed only pain‐related school absence to be associated with physician consultation; analgesic medication use was associated with school absence and higher pain intensity.

Conclusion

Original data from this study support prior findings. School absence and pain intensity, plausible surrogates for pain severity, are the most relevant factors in health care utilisation due to chronic pain.

Significance

A scoping summary of existing research on predictors for physician consultation and medication use in children and adolescents with chronic pain is provided. Furthermore, the role of potential predictors for health care utilisation—sociodemographic, pain, school, psychological and parent‐related characteristics—is analysed in a population‐based cross‐sectional survey. Controlling for illness and injuries, and using a strict chronic pain definition, the cross‐sectional survey allows conclusions on healthcare utilisation specific to chronic pain in adolescents.



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Physiologic osteoclasts are not sufficient to induce skeletal pain in mice

Abstract

Background

Increased bone resorption is driven by augmented osteoclast activity in pathological states of the bone, including osteoporosis, fracture and metastatic bone cancer. Pain is a frequent co‐morbidity in bone pathologies and adequate pain management is necessary for symptomatic relief. Bone cancer is associated with severe skeletal pain and dysregulated bone remodelling, while increased osteoclast activity and bone pain are also observed in osteoporosis and during fracture repair. However, the effects of altered osteoclast activity and bone resorption on nociceptive processing of bone afferents remain unclear.

Methods

This study investigates whether physiologic osteoclasts and resulting changes in bone resorption can induce skeletal pain. We first assessed correlation between changes in bone microarchitecture (through µCT) and skeletal pain using standardized behavioural phenotyping assays in a mouse model of metastatic bone cancer. We then investigated whether increased activity of physiologic osteoclasts, and the associated bone resorption, is sufficient to induce skeletal pain using mouse models of localized and widespread bone resorption following administration of exogenous receptor activator of nuclear factor kappa‐B ligand (RANKL).

Results

Our data demonstrates that mice with bone cancer exhibit progressive pain behaviours that correlate with increased bone resorption at the tumour site. Systemic RANKL injections enhance osteoclast activity and associated bone resorption, without producing any changes in motor function or pain behaviours at both early and late timepoints.

Conclusion

These findings suggest that activation of homeostatic osteoclasts alone is not sufficient to induce skeletal pain in mice.

Significance statement

The role of osteoclasts in peripheral sensitization of sensory neurones is not fully understood. This study reports on the direct link between oestrogen‐independent osteoclast activation and skeletal pain. Administration of exogenous receptor activator of nuclear factor kappa‐B ligand (RANKL) increases bone resorption, but does not produce pro‐nociceptive changes in behavioural pain thresholds. Our data demonstrates that physiologic osteoclasts are not essential for skeletal pain behaviours.



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Pain, sensitization and physical performances in patients with chronic painful knee osteoarthritis or chronic pain following total knee arthroplasty: An explorative study

Abstract

Background

The aim of this study was to assess clinical pain, pain sensitization and physical performances to profile patients with chronic painful knee osteoarthritis (OA) or pain after total knee arthroplasty (TKA). Examining the interactions between pain mechanisms and physical performances would enable us to investigate the underlying explanatory relationships between these parameters.

Methods

In this explorative study, 70 patients with chronic painful knee OA (N = 46) or chronic pain after TKA (N = 24) were assessed for clinical pain, quantitative sensory profiling (mechanical pinprick pain sensitivity, temporal summation (TS) and conditioned pain modulation), physical performances (chair stand, walk and stair climb tests) and self‐reported outcomes. Between‐group comparisons were made using ANCOVA tests and associations between outcomes were analysed using multivariate linear regression models.

Results

Overall, no differences between groups regarding clinical pain and quantitative sensory profiling outcomes were observed. Physical performances were lower in the TKA group compared with the OA group with moderate‐to‐large effect sizes, and a tendency towards better scores in self‐reported outcomes for the OA group was observed with small‐to‐moderate effect sizes. Self‐reported function seems to be associated with physical performances in the TKA group. Sensitization (TS) appears to be associated with poorer physical performances in the OA group.

Conclusions

Similar profiles for pain intensity, signs of sensitization and conditioned pain modulation were observed. Patients with TKA seems to have impaired physical performances compared with the OA group, underlining the importance of targeting physical performances. Only the OA patients showed an association between sensitization (TS) and physical performance.

Significance

Quantitative pain profiling assessment was used to assess pain intensities and pain mechanisms. We observed associations between physical performances and temporal summation in the OA group underlining the importance of assessing motor functions and pain mechanisms in the same trial. We observed lower levels of physical performances in the TKA group compared with the OA group, suggesting that examination and rehabilitation of physical performances is essential for TKA patients with chronic pain.



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Overactivity assessment in chronic pain: The development and psychometric evaluation of a multifaceted self‐report assessment

Abstract

Background

Overactivity in the context of chronic pain (i.e. activity engagement that significantly exacerbates pain) is an important clinical issue that has gained empirical attention in the last decade. Current assessment concepts of overactivity tend to focus on frequency to quantify the severity of the pain behaviour. This study aimed to develop and validate a more comprehensive self‐assessment, the Overactivity in Persistent Pain Assessment (OPPA).

Methods

A sample of 333 individuals with chronic pain completed the OPPA. A subset of 202 individuals also completed a set of existing measures of pain‐related outcomes and activity patterns. The remaining 131 participants were provided with a second copy of the OPPA to fill in one week following their initial assessment.

Results

A principal component analysis confirmed that the OPPA items were best represented by a single construct. The OPPA was found to correlate with pain‐related measures in an expected way that is supported by both theory and qualitative data. When compared to existing overactivity measures, the OPPA was the only measure to contribute significantly to the regression models predicting higher levels of pain severity, more pain interference and lower levels of activity participation after controlling for age, gender and activity avoidance. In addition, the OPPA scale exhibited acceptable internal consistency and good test–retest reliability.

Conclusion

The results of this study reinforce the potentially important role of overactivity in the maintenance of pain‐related suffering and supports a corresponding assessment tool with preliminary psychometric evidence for clinical and research applications.

Significance

This study deconstructs the overactivity concept and develop a corresponding assessment based on five quantifiable severity features: severity of pain exacerbation, maladaptive coping strategies used, impact on occupational performance, recovery time and frequency. Results of the psychometric evaluation indicate that this comprehensive assessment of overactivity severity features may be necessary to understand the impact of overactivity on pain severity and physical functioning from both a clinical and research perspective.



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Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults

Abstract

Background

Conditioned pain modulation (CPM) methods are experimental procedures to assess presumed descending nociceptive modulatory pathways. Various CPM‐methods are currently used, making the comparison of results difficult. The aim of this study was to compare five conditioning stimuli and to evaluate the influencing effects of personal factors on CPM‐efficacy.

Methods

101 healthy pain‐free adults (50 males, 51 females) participated in this cross‐sectional study with repeated measures design. The CPM‐method consisted of hot water immersion (46°C, HWI), cold pressor test (12°C, CPT), cold pack application, and single and double ischemic occlusion as conditioning stimuli in randomized order. Pressure pain threshold was used as test stimulus at the mm. trapezius and quadriceps for all CPM‐protocols.

Results

All CPM‐protocols resulted in effective CPM, although cold pack application revealed smaller CPM‐magnitudes compared to all other methods at both muscles, except single ischemic occlusion at the m. quadriceps. A smaller CPM‐effect at the m. trapezius was shown when CPM was provoked by single ischemic occlusion compared to the CPT. Chronic stress, gender, attentional focus, age, physical activity and perceived pain are all influencing factors, in various conditioning stimuli at the mm. trapezius and quadriceps.

Conclusions

CPT and HWI seem to be the most appropriate conditioned pain modulation paradigms for research settings, while single and double ischemic occlusion seem to be more useful for clinical settings. Influencing factors to be considered are gender, age, stress, physical activity, perceived pain and attentional focus to the conditioning stimulus, but depend on the test site and exerted method.

Significance

Hot water immersion, cold pressor test, and single and double ischemic occlusion result in comparable CPM‐effects at the mm. trapezius and quadriceps. Anti‐nociceptive effects of the cold pack are mainly a result of attention towards the cold pack. Chronic stress, attentional focus towards the conditioning stimulus and perceived pain of the conditioning stimulus influenced the anti‐nociceptive effects at the m. trapezius. Gender and level of physical activity influenced the anti‐nociceptive effects with the other methods at the m. quadriceps.



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Prescription of exercises for the treatment of chronic pain along the continuum of nociplastic pain: A systematic review with meta‐analysis

Abstract

Background and Objective

To compare different exercise prescriptions for patients with chronic pain along the continuum of nociplastic pain: fibromyalgia, chronic whiplash‐associated disorders (CWAD), and chronic idiopathic neck pain (CINP).

Databases and Data Treatment

Randomized controlled trials comparing different exercise parameters were included. The search was performed in the databases Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PEDro. Data on the parameters for the physical exercise programs for pain management were extracted for analysis.

Results

Fifty studies with 3,562 participants were included. For fibromyalgia, both aerobic strengthening exercises were similar and better than stretching exercises alone. Exercises could be performed in 50‐ to 60‐min supervised sessions, 2 to 3 times a week, for 13 weeks or more. For CWAD, body awareness exercises were similar to combined exercises, and there was no difference in adding sling exercises to a strengthening exercise program. The exercises could be performed in 90‐min supervised sessions, twice a week, for 10 to 16 weeks. For CINP, motor control exercises and nonspecific muscle strengthening had a similar effect. Exercises could be performed in 30‐ to 60‐min supervised sessions, 2 to 3 times a week, for 7 to 12 weeks.

Conclusions

The choice of parameters regarding exercises should emphasize global exercises in nociplastic pain conditions (such as fibromyalgia and CWAD) and specific exercises in non‐nociplastic pain conditions (such as CINP) and be based on patient's preference and therapist's skills.

Prospero registration number

CRD42019123271.

Significance

The pain mechanism must be considered to optimize exercise prescription in patients with different chronic pain profiles. The main message of this article is that low to moderate intensity global exercises performed for a long period of treatment should be performed in patients with nociplastic pain predominance. Additionally, focused and intense exercises for a short period of treatment can be prescribed for patients with nociceptive pain predominance.



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Corrigendum

European Journal of Pain, Volume 25, Issue 1, Page 272-272, January 2021.

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Psychosocial factors associated with pain and sexual function in women with Vulvodynia: A systematic review

Abstract

Background and objective

Vulvodynia is a prevalent chronic vulval pain condition affecting 10%–28% of women, and significantly impacting their health and quality of life. It is currently poorly understood and biomedical treatments achieve only modest benefits for pain and sexual functioning. A wider psychosocial conceptualization of this condition may improve outcomes. There is currently no coherent understanding of how psychosocial factors may contribute to outcomes in Vulvodynia. The aim of this review is to identify and systematically review psychosocial factors associated with pain and sexual outcomes and to inform a psychosocial model of Vulvodynia.

Databases and data treatment

Observational/experimental studies reporting on the association between psychosocial factors and pain/sexual outcomes in adult women with Vulvodynia were eligible. Two reviewers independently conducted eligibility screening, data extraction and quality assessment. Twenty‐one studies were included, all focused on women with Provoked Vestibulodynia (PVD). Most of the studies were low‐to‐medium quality.

Results/Conclusion

A range of general/pain‐related distress and avoidance processes, and sex/intimacy avoidance or engagement processes were significantly associated with pain, sexual functioning or sexual distress and sexual satisfaction, supporting the role of a psychosocial approach to PVD. Depression, anxiety, catastrophizing, pain‐anxiety, pain acceptance, body‐exposure anxiety, attention to sexual cues, partner hostility and solicitousness, self‐efficacy and penetration cognitions are highlighted as potentially important treatment targets in PVD. Due to the limited data available, developing a psychosocial model was not possible. Directions for future research include examining the replicability and generalizability of the factors identified, exploring differences/similarities across Vulvodynia subsets and testing tailored theoretically based treatments.

Significance

The systematic review highlights the role of psychosocial factors associated with pain and sexual functioning in Vulvodynia. The review findings reveal that Vulvodynia presents both similar and unique cognitive, behavioural and interpersonal features compared to other chronic pain conditions. There may be important roles for negative sexual cues, body image–related factors during intercourse, partner factors, self‐efficacy beliefs and penetration cognitions, in relation to pain and sexual functioning.



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Exploring the contextual role of pain severity as a moderator of the relationship between activity patterns and the physical and mental functioning of women with fibromyalgia

Abstract

Introduction

In past years, and mostly due to contextual psychological therapies, it has been argued that particular behavioural patterns may be useful in certain contexts, but not in others. The goal of this study has been to explore whether pain severity is indeed a contextual factor influencing the relationship between two controversial activity patterns, namely pacing and persistence, and functionality in people with fibromyalgia.

Methods

Participants were 231 women diagnosed with fibromyalgia. A multivariate regression was conducted to explore the moderating role of pain severity in the relationship between activity patterns and outcomes (i.e. fibromyalgia impact and depressive symptoms).

Results

Excessive persistence (interaction: = −2.45, p = 0.015) and pain‐contingent persistence (interaction: t= −2.13, p = 0.034) were more strongly associated with fibromyalgia impact when people experienced less severe pain. Pacing for pain reduction was only significantly related to depressive symptoms at very severe (M = 10) pain levels (interaction: β= −0.18, t= −2.73).

Conclusions

The results here reported suggest that the context in which behaviour occurs is relevant when the utility of certain behaviour patterns is considered. The clinical implications of this are clear, as it would justify adapting the recommendations given to patients according to their pain severity status.

Significance

This manuscript shows that some activity patterns (i.e. pacing to conserve energy for valued activities) might be advisable regardless of pain levels. Conversely, some patterns might be especially recommended (i.e. pain‐reduction pacing) or inadvisable (i.e. excessive and pain‐contingent persistence) depending on pain levels (i.e. severe and mild pain, respectively).



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Thursday, December 17, 2020

[Correspondence] Management of primary spontaneous pneumothorax: less is more – Authors' reply

We thank Simon Brown and colleagues for their comments regarding our study.1 We agree that generally less is more in terms of management of primary spontaneous pneumothorax and that, together, our two randomised studies provide important data that should be incorporated into future guidelines.1,2 However, we feel that the studies might reflect two differing populations of patients with primary spontaneous pneumothorax. The median scores for pain and breathlessness at enrolment in Brown and colleagues' study2 were lower (interventional group: pain 2/10 and breathlessness 1/10; conservative group: pain 2/10 and breathlessness 1/10) than in our study1 (ambulatory group: pain 41/100 and breathlessness 43/100; standard care group: pain 37/100 and breathlessness 41/100).

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Wednesday, December 16, 2020

Dependence‐like behaviour in patients treated for medication overuse headache: A prospective open‐label randomized controlled trial

Abstract

Background

Dependence‐like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence‐like behaviour is unknown.

Objectives

To compare patient‐reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to six months.

Methods

Patients with MOH were randomized to 1) withdrawal combined with preventive medication from start (W+P), 2) preventive medication without withdrawal (P), or 3) withdrawal with optional preventive medication two months after withdrawal (W). At baseline, two, and six months, patients filled out SDS (used for measurements of dependence‐like behaviour and treatment feasibility), Headache Under‐Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires.

Results

Out of 120 patients with MOH, 100 completed the six‐month follow‐up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After six months, the SDS score was reduced by 3.69 (95 % CI 3.23 to 4.49) in the W+P arm, by 3.19 (95 % CI 2.43 to 3.96) in the W arm, and by 1.65 (95 % CI 0.96 to 2.33) in the P arm (P = 0.04). At baseline and after two months, the P arm was considered the most feasible treatment, but at six‐month follow‐up, there was no difference in feasibility score, change in HURT score, or quality of life.

Conclusions

Dependence‐like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH.



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Medication and Healthcare Utilisation Variation Among Older Adults with Pain

Abstract

Background

While pain is very common in older adults, the associated impact on daily life, including usage of medication and healthcare, varies considerably and often pain remains inadequately treated. It is not clear what is associated with this variation.

Methods

Latent class analysis (LCA) is a model‐based approach to identifying underlying subgroups in a population. In this study LCA was used to examine biopsychosocial risk classes of adults aged 50 years and older, who were often troubled by pain, from The Irish Longitudinal Study on Ageing (TILDA), (n=2,896), and the associations with future medication and healthcare use.

Results

Four biopsychosocial risk classes (Low Biopsychosocial Risk, Physical Health Risk, Mental Health Risk, High Biopsychosocial Risk) were identified, with the ‘High Biopsychosocial Risk’ class accounting for 24% of older adults with pain. This class were much more likely to use medication and healthcare services when followed up across three waves of the TILDA study. In contrast, the Physical Health Risk and the Mental Health Risk classes reported lower usage of medication and healthcare at waves 2 and 3. Amongst the higher risk classes of older adults who are troubled by pain, there is considerable consumption of medication and healthcare services evident.

Conclusion

Given our ageing population and significant number of adults in this high risk class, there is a need to optimise current pain management approaches among older adults. Intensive non‐pharmacological approaches to pain management in older adults, tailored to individual biopsychosocial risk indicators for each individual class, may be worth exploring.



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Widespread myofascial dysfunction and sensitization in women with endometriosis‐associated chronic pelvic pain: A cross‐sectional study

Abstract

Background

Chronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.

Objective

Characterize the presence and distribution of pain, myofascial dysfunction, and sensitization beyond the pelvis in women with endometriosis‐associated chronic pelvic pain.

Methods

Cross‐sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain‐focused abdominopelvic gynecologic examination with identification of pelvic floor muscle spasm. Neuro‐musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger‐points in 13 paired muscles. Pressure‐pain thresholds were measured over interspinous ligaments and trigger‐points. Women completed the body territories element of the Body Pain Index.

Results

All women had pelvic floor muscle spasm that they self‐identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure‐pain thresholds and trigger‐points in over two‐thirds of 26 assessed regions. Widespread spinal segmental sensitization was present in 17/30, thoracic in 21/30, and lumbosacral/pelvic in 18/30. Cervical sensitization manifested as low pressure‐pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p=.024) and lumbosacral/pelvic (p=.036) sensitization and report over 10 painful body areas (p=.009).

Conclusions

Women with endometriosis‐associated chronic pelvic pain often have myofascial dysfunction and sensitization beyond the pelvic region that may be initiated or maintained by on‐going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population.



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The effect of optimism on facial expression of pain: Implications for pain communication

Abstract

Background

There is a broad range of evidence on optimism dampening the pain experience, as assessed by subjective self‐report. Facial expression of pain conveys supplementary information about the pain experience, is an integral part of pain communication and assists psychosocial pain coping. Nevertheless, the effect of induced optimism on facial activity during pain has to our knowledge not been examined.

Methods

In our experiment, 40 healthy participants underwent two blocks of thermal stimulation containing phasic non‐painful and painful stimuli. Between the two blocks, the Best Possible Self imagery and writing task was performed to induce situational optimism, while a control group wrote about their typical day. Facial activity and self‐report ratings of intensity and unpleasantness were recorded. Facial activity was analyzed using the Facial Action Coding System.

Results

The optimism manipulation was successful in increasing state optimism. It did not affect self‐report ratings, but resulted in a stronger facial expression of pain, caused especially by increases in Action Units 4 (furrowed brows) and 6_7 (narrowed eyes).

Conclusions

All Action Units, which were affected by the optimism induction, are known to be prevalent during pain stimulation. The increase in facial expression might reflect reduced inhibition of pain communication in temporarily optimistic participants. Optimism might lead to expecting positive and helpful reactions by others and, by that, to great readiness to elicit these reactions by non‐verbal social behavior.



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Widespread myofascial dysfunction and sensitization in women with endometriosis‐associated chronic pelvic pain: A cross‐sectional study

Abstract

Background

Chronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.

Objective

Characterize the presence and distribution of pain, myofascial dysfunction, and sensitization beyond the pelvis in women with endometriosis‐associated chronic pelvic pain.

Methods

Cross‐sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain‐focused abdominopelvic gynecologic examination with identification of pelvic floor muscle spasm. Neuro‐musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger‐points in 13 paired muscles. Pressure‐pain thresholds were measured over interspinous ligaments and trigger‐points. Women completed the body territories element of the Body Pain Index.

Results

All women had pelvic floor muscle spasm that they self‐identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure‐pain thresholds and trigger‐points in over two‐thirds of 26 assessed regions. Widespread spinal segmental sensitization was present in 17/30, thoracic in 21/30, and lumbosacral/pelvic in 18/30. Cervical sensitization manifested as low pressure‐pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p=.024) and lumbosacral/pelvic (p=.036) sensitization and report over 10 painful body areas (p=.009).

Conclusions

Women with endometriosis‐associated chronic pelvic pain often have myofascial dysfunction and sensitization beyond the pelvic region that may be initiated or maintained by on‐going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population.



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The effect of optimism on facial expression of pain: Implications for pain communication

Abstract

Background

There is a broad range of evidence on optimism dampening the pain experience, as assessed by subjective self‐report. Facial expression of pain conveys supplementary information about the pain experience, is an integral part of pain communication and assists psychosocial pain coping. Nevertheless, the effect of induced optimism on facial activity during pain has to our knowledge not been examined.

Methods

In our experiment, 40 healthy participants underwent two blocks of thermal stimulation containing phasic non‐painful and painful stimuli. Between the two blocks, the Best Possible Self imagery and writing task was performed to induce situational optimism, while a control group wrote about their typical day. Facial activity and self‐report ratings of intensity and unpleasantness were recorded. Facial activity was analyzed using the Facial Action Coding System.

Results

The optimism manipulation was successful in increasing state optimism. It did not affect self‐report ratings, but resulted in a stronger facial expression of pain, caused especially by increases in Action Units 4 (furrowed brows) and 6_7 (narrowed eyes).

Conclusions

All Action Units, which were affected by the optimism induction, are known to be prevalent during pain stimulation. The increase in facial expression might reflect reduced inhibition of pain communication in temporarily optimistic participants. Optimism might lead to expecting positive and helpful reactions by others and, by that, to great readiness to elicit these reactions by non‐verbal social behavior.



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Friday, December 11, 2020

Increased salience network connectivity following manual therapy is associated with reduced pain in chronic low back pain patients

Chronic low back pain (cLBP) has been associated with changes in brain plasticity. Non-pharmacological therapies such as Manual Therapy (MT) have shown promise for relieving cLBP. However, translational neuroimaging research is needed to understand potential central mechanisms supporting MT. We investigated the effect of MT on resting-state salience network (SLN) connectivity, and whether this was associated with changes in clinical pain.Fifteen cLBP patients, and 16 matched healthy controls (HC) were scanned with resting functional Magnetic Resonance Imaging (fMRI), before and immediately after a MT intervention (cross-over design with two separate visits, pseudorandomized, grades V ‘Manipulation’ and III ‘Mobilization’ of the Maitland Joint Mobilization Grading Scale).

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Thursday, December 10, 2020

[Editorial] Facing up to long COVID

Multiorgan symptoms after COVID-19 are being reported by increasing numbers of patients. They range from cough and shortness of breath, to fatigue, headache, palpitations, chest pain, joint pain, physical limitations, depression, and insomnia, and affect people of varying ages. At the Lancet–Chinese Academy of Medical Sciences conference on Nov 23, Bin Cao presented data (in press at The Lancet) on the long-term consequences of COVID-19 for patients in Wuhan, and warned that dysfunctions and complications could persist in some discharged patients for at least 6 months.

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[Clinical Picture] Occult fracture in teenager's tibia revealed by MRI

A 13-year-old girl presented with a 2-week history of mild pain in her right knee. She reported no recent injury. x-rays showed a high-density linear abnormality with a periosteal reaction in the proximal right tibia (figure), which medical staff, at the hospital where she was first seen, thought might have been a tumour of the bone.

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Modeling at‐level allodynia after mid‐thoracic contusion in the rat

Abstract

The rat mid‐thoracic contusion model has been used to study at‐level tactile allodynia, a common type of pain that develops after spinal cord injury (SCI). An important advantage of this model is that not all animals develop hypersensitivity. Therefore, it can be used to examine mechanisms that are strictly related to the development of pain‐like behavior separately from mechanisms related to the injury itself. However, how to separate animals that develop hypersensitivity from those that do not is unclear. The aims of the current study were to identify where hypersensitivity and spasticity develop and use this information to identify metrics to separate animals which develop hypersensitivity from those that do not to study differences in their behavior. To accomplish these aims, a grid was used to localize hypersensitivity on the dorsal trunk relative to thoracic dermatomes, and supraspinal responses to tactile stimulation were tallied. These supraspinal responses were used to develop a hypersensitivity score to separate animals that develop hypersensitivity, or pain‐like response to nonpainful stimuli. Similar to humans, the development of hypersensitivity could occur with the development of spasticity or hyperreflexia. Moreover, the time course and prevalence of hypersensitivity phenotypes (at‐, above‐, or below level) produced by this model were similar to that observed in humans with SCI. However, the amount of spared spinal matter in the cord did not explain the development of hypersensitivity, as previously reported. This approach can be used to study the mechanisms underlying the development of hypersensitivity separately from mechanisms related to injury alone.



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The influence of physical activity on the nociceptive flexion reflex in healthy people

ABSTRACT

Background

The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in an appropriate withdrawal response. The NFR is considered to be an objective physiological correlate of spinal nociception. Previous research has already demonstrated that physical activity (PA) can influence pain assessments. To date, no studies have directly examined the relationship between PA and spinal nociception. Hence, this study aimed to investigate whether the NFR threshold can be predicted by report‐based and monitor‐based measures of PA in healthy adults.

Methods

PA and the NFR threshold of 58 healthy adults were assessed. PA was evaluated by self‐report using the International Physical Activity Questionnaire and by monitor‐based accelerometry data. The NFR threshold was elicited through transcutaneous electrical stimulation of the sural nerve and quantified by the biceps femoris muscle electromyogram. Hierarchical linear regression analyses were performed to determine the relationship between PA and the NFR, while controlling for confounders.

Results

Monitor‐based measured step count and activities of moderate‐vigorous intensity predicted the NFR threshold accounting for 23.0% (p=0.047) to 37.1% (p=0.002) of the variance. Larger amounts of step counts and higher participation in moderate‐vigorous intensity activities predicted higher NFR thresholds. Monitor‐based activities of sedentary intensity predicted the NFR threshold accounting for 35.8% (p=0.014) to 35.9% (p=0.014) of the variance. Spending more time per day on activities of sedentary intensity predicted lower NFR thresholds.

Conclusions

The study provides preliminary evidence indicating that a physically active lifestyle may reduce spinal nociception in healthy adults, while a sedentary lifestyle enhances spinal nociception.



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Offset analgesia is reduced on the palm and increases with stimulus duration

Abstract

Background

A noxious stimulus following a more intense stimulus often feels less painful than continuous noxious stimulation. This effect, known as offset analgesia (OA), may be due to descending inhibitory control, to changes in peripheral neural transmission, or both. The timing and location of noxious thermal stimulation were manipulated to better understand the peripheral and central contributions to OA.

Methods

In a first experiment, participants (n=29) provided continuous pain ratings as stimuli were delivered to the palm or dorsum of each hand. Offset trials included 44 °C (T1), 45 °C (T2), and 44 °C (T3) stimulation periods. Baseline trials were identical except the T3 temperature fell to 35 °C. Constant trials were 44 °C throughout. The duration of T1 and T2 was either 1s or 6s, whereas T3 was always 12s. In a second experiment, participants (n=43) rated pain levels of noxious stimuli presented to the forearms with varying T1 and T2 durations (3, 6, 10 or 13s) and a 20s T3 period.

Results

OA effects became stronger with increasing inducing durations. OA, however, was not found on the palm even at longer durations.

Conclusions

The increase of OA with duration suggests that accumulated nociceptive signalling is more important to triggering OA than is a decrease in nociceptors’ instantaneous firing rates. The lack of OA on the palm, however, implies a key role for the rapidly adapting Type II AMH fibres that may be absent or not readily activated on the palm. Unravelling the relative central and peripheral contribution to OA requires further investigation.



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Herpes Zoster Duplex Unilateralis as a manifestation of severe lymphopenia in COVID19

Abstract

SARS‐CoV2 (severe acute respiratory syndrome coronavirus‐2) , a novel coronavirus was first reported in December of 2019 from Wuhan, China as an etiological agent causing a new infectious respiratory disease (coronavirus disease 2019‐ COVID‐19). The main clinical manifestations of COVID‐19 are fever, cough, fatigue, dyspnoea and muscle aches.



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A traumatic elbow injury

A 4 year old boy presented with pain in his right elbow after a fall from a bicycle onto his outstretched hand. His father had noticed him lying on his arm after the fall. The patient was guarding...


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Transcutaneous Electric Nerve Stimulation reduces acute postoperative pain and analgesic use after open inguinal hernia surgery: a randomized, double-blind, placebo-controlled trial

Worldwide, more than 20 million patients undergo inguinal hernia repair annually.25 Open tensionless repair techniques will be an important treatment for the foreseeable future.32 Lichtenstein repair is widely considered the “gold standard” in open tensionless inguinal hernia repair. Since the introduction of meshes, recurrence rates have decreased, with a current occurrence rate 1-2%, and great attention has been directed to postoperative acute and chronic pain treatment.22 Acute pain is the most common complaint reported by patients following inguinal hernia repair.

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Wednesday, December 9, 2020

OPTIMIZATION OF SPINAL MANIPULATIVE THERAPY PROTOCOLS: A FACTORIAL RANDOMIZED TRIAL WITHIN A MULTIPHASE OPTIMIZATION FRAMEWORK

Low back pain (LBP) is among the most common health conditions and a leading cause of disability globally.1, 38 The adverse societal impacts of ineffective LBP management are increasingly recognized. Back pain is the most costly health condition in the United States and is the most common diagnosis for which opioids are prescribed.22, 70 Practice guidelines recommend nonpharmacological treatment (NPT) for pain conditions including LBP.18, 23, 58 While many NPTs are effective for LBP, the magnitude of effects are small and highly heterogeneous within groups of patients.

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Cross-sectional study of prevalence, characterization and impact of chronic pain disorders in workers

The risks of developing a chronic disease increase when the psychosocial environment is unfavorable and repetitive physical efforts are added, for example, through handling work and static postures14,33. An unfavorable psychosocial environment corresponds to working conditions that may lead to psychosocial risks, for example: overwork and stress; conflicting requirements and lack of clarity about the missions to be performed; insufficient involvement of workers in decisions affecting them and their careers; insufficient management of job changes and job insecurity; insufficient communication and support from management or colleagues; psychological and sexual harassment.

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Thursday, December 3, 2020

[Perspectives] Things shameful to be spoken about

I'll tell you a secret: the day I graduated from medical school was the happiest day of my life. I was happy on my wedding day, but I threw up as soon as my husband and I arrived at our hotel after the reception—something I've never confided to anyone before. I was happy, too, of course, on the days I gave birth to my children, but that happiness was alloyed with pain and fear. The day I became a doctor I experienced no pain or fear or even gastrointestinal upset—those would come just a few weeks later when I started internship.

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[Clinical Picture] Primary herpes simplex virus type 2 hepatitis diagnosed during laparoscopy

A 31-year-old woman presented to our hospital with a 1-week history of fever, myalgia, and right upper quadrant abdominal pain. She had no significant medical history, history of recent travel, or alcohol use. She reported no genitourinary symptoms, rashes, oral ulcerations, or pharyngitis. She did say that she had been recently sexually active with a new male partner.

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Wednesday, December 2, 2020

Preoperative risk factors associated with chronic pain profiles following total knee arthroplasty

ABSTRACT

Background

One in five patients experiences chronic pain 12 months following total knee arthroplasty (TKA). This longitudinal study used a person‐centered approach to identify subgroups of patients with distinct chronic pain profiles following TKA and identified preoperative characteristics associated with these profiles.

Methods

On the day before surgery, 202 patients completed questionnaires that assessed pain, interference with functioning, fatigue, anxiety, depression, and illness perceptions. Average and worst pain were assessed prior to surgery, on postoperative day 4, at 6 weeks, and at 3 and 12 months following surgery. Using growth mixture modeling, two subgroups with distinct average and worst pain profiles were identified.

Results

Patients in the “lower average” and “lower worst” pain classes had moderate preoperative pain scores that decreased over the remaining 9 months following TKA. Patients in the “higher average” and “higher worst” pain classes had relatively higher preoperative pain scores that increased during the first three months and then decreased slightly over the remaining 9 months. Patients in the higher pain classes had higher interference with function scores; used opioids prior to surgery more often, were more likely to receive a continuous nerve block and ketamine; had higher preoperative fatigue severity and interference scores; and had worse perceptions of illness than patients in the lower pain classes.

Conclusions

These risk factors may be used to identify subgroups of patients at higher risk for more severe pain after TKA. Future studies should test whether modifying these risk factors can improve patients’ outcomes after TKA.



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Development and Validation of a Daily Injustice Experience Questionnaire

Abstract

Background

Patterns of cognitive appraisal related to chronic pain may manifest differentially across time due to a variety of factors, but variability of injustice appraisals across time has not been examined. The current study details the validation of a brief, daily version of the Injustice Experience Questionnaire (IEQ), which measures injustice appraisals related to the experience of pain and disability.

Methods

IEQ items were adapted for daily use and evaluated using cognitive interviews, and the resulting measure was administered for 10 days to 2 Internet‐based samples of US adults with cLBP.

Results

Study 1 (N = 126) refined the 12‐item IEQ measure into a 6‐item short form; exploratory factor analyses suggested optimal model fit for the 2‐factor model established in the original IEQ. Using confirmatory factor analyses, Study 2 (N = 131) replicated the 2‐factor structure and demonstrated significant correlations of the Daily IEQ with other relevant constructs to chronic pain, such as pain catastrophizing, pain intensity, pain‐related activity and social interference, depressed mood, and anxiety. Daily IEQ items showed a significant degree of clustering (intraclass correlations ranging from .577 to .735) but demonstrated sufficient variability at the daily level to allow for daily‐level analysis.

Conclusions

Injustice appraisals show a sufficient degree of daily variability to warrant their measurement as a time‐varying construct. Further examination of antecedents and correlates of daily injustice appraisals, as well as their potential role as mechanisms of effect, may better explain the dynamics of affective and behavioral responses to chronic pain.



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Early life chronic inflammatory conditions predict low back pain in adolescence and young adulthood

Abstract

Background

Associations between inflammatory conditions and low back pain (LBP) have been found frequently in older populations. However, the nature of these relationships in younger populations is unknown. This study aimed to investigate associations between early life chronic or recurrent inflammatory conditions and impactful LBP in adolescence and young adulthood.

Methods

In this longitudinal study we used data from the Raine Study Gen2 participants at the 1,2,3,5,8,10,14,17,20, and 22‐year follow‐ups (N=2868). Data were collected on inflammatory conditions from one to 22‐years of age and occurrences of impactful LBP from 14 to 22‐years of age. Longitudinal and cross‐sectional associations between inflammatory conditions and impactful LBP occurrence were examined. Potential dose response relationships between the number of inflammatory conditions and impactful LBP were also assessed. Logistic regression models were used in the analysis.

Results

Participants with respiratory or atopic conditions during childhood had increased odds of future impactful LBP in adolescence and young adulthood (odds ratio(OR)[95% confidence interval (CI)] = 1.29[1.07, 1.54], 1.23[1.02, 1.49] respectively). There were cross‐sectional associations between inflammatory conditions including respiratory, skin, musculoskeletal, autoimmune, and atopic conditions, with impactful LBP. Participants with two illnesses and three or more illnesses had an increased odds (OR[95% CI] = 1.68[1.30, 2.18]) and (OR[95% CI] = 2.12[1.54, 2.89]) respectively of reporting impactful LBP.

Conclusions

Overall, longitudinal and cross‐sectional associations of respiratory and atopic conditions with impactful LBP in adolescence and young adulthood were identified. More evidence is needed to determine if there is a causal relationship between chronic inflammatory conditions and impactful LBP.



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Child pain‐related injustice appraisals mediate the relationship between just‐world beliefs and pain‐related functioning

ABSTRACT

Background

Research among adult and pediatric 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 2174 children (Study 1) and a clinical sample of 146 pediatric 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.



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Impact of Check of Medication Appropriateness (CMA) in optimizing analgesic prescribing: an interrupted time series analysis

Abstract

Background

Pain therapy in inpatients is regularly suboptimal and might be improved by clinical pharmacy services. In our hospital, we have implemented a software‐supported ‘Check of Medication Appropriateness’ (CMA), which is a centralized pharmacist‐led service consisting of a clinical rule‐based screening for potentially inappropriate prescriptions (PIPs), and a subsequent medication review by pharmacists. We aimed to investigate the impact of the CMA on pain‐related prescribing.

Methods

A quasi‐experimental study was performed in a large teaching hospital, using an interrupted time series design. Pre‐implementation, patients were exposed to standard of care. Afterwards, a pain‐focused CMA comprising 12 specific clinical rules pertaining to analgesic prescribing were implemented in the post‐implementation period. A regression model was used to assess the impact of the intervention on the number of pain‐related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the post‐implementation period.

Results

At baseline, a median number of 13.1 (range: 9.5‐15.8) residual PIPs per day was observed. After the CMA intervention, the number was reduced to 2.2 (range: 0‐9.5) per day. Clinical rules showed an immediate relative reduction of 66% (p<0.0001) in pain‐related residual PIPs. A significant decreasing time trend was observed during the post‐implementation period. Post‐implementation, 1683 recommendations were given over one year with an acceptance rate of 74.3%.

Conclusions

We proved that the CMA approach reduced the number of pain‐related residual PIPs. More pharmacist involvement and the use of clinical rules during hospital stay should be further promoted to optimize appropriate prescribing of analgesics.



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Tuesday, December 1, 2020

Altered regulation of negative affect in patients with fibromyalgia: A diary study

Abstract

Background

Fibromyalgia is characterized by widespread musculoskeletal pain and often accompanied by cognitive and emotional problems. Adaptation to fibromyalgia may therefore also rely on one’s ability to regulate emotional problems. In this study, we examined two indices of emotion regulation, i.e., (1) affective instability, involving frequent large fluctuations in self‐reported affect, and (2) resting heart rate variability (HRV).

Methods

Participants were 46 patients with fibromyalgia (M age = 45.4 years; 39 females) and 46 matched healthy controls (M age = 44.9 years; 37 females). Heart rate was monitored under resting conditions to derive HRV. Subsequently, participants completed an electronic end‐of‐day diary for 14 consecutive days assessing daily levels of pain, disability, negative affect (NA) and positive affect (PA). Affective instability was operationalized as the mean square of successive differences in daily mood.

Results

Results indicate increased levels of NA instability and reduced levels of HRV in patients with fibromyalgia in comparison with healthy controls. Furthermore, HRV and NA instability were inversely related. Finally, in patients, higher NA instability was related to increased pain disability.

Conclusions

Current findings support the idea that patients with fibromyalgia are confronted with fluctuating emotions. These results may have important implications for treatment as they provide support for the use of emotion regulation skills training in patients with fibromyalgia to impact upon NA instability.



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A linguistic analysis of future narratives in adolescents with Complex Regional Pain Syndrome and their pain‐free peers

Abstract

Background

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that often develops after injury, with a typical onset in adolescence. The impact of chronic pain is far‐reaching, with many adolescents reporting atypical developmental trajectories compared with peers. Social Comparison Theory offers a framework for understanding how such comparisons influence wellbeing, whereby a heightened sense of disparity places adolescents at risk of poor cognitive, affective and social outcomes. Using a novel linguistic analysis programme, this study aims to investigate cognitive, affective and social language used by adolescents with CRPS in comparison to their peers during a task reflecting on their futures.

Methods

A story completion task was completed by adolescents with CPRS (n=49) and adolescents without pain (n=48). This task involved asking adolescents to describe their imagined future. Narratives were analysed using a novel linguistic analysis programme, focusing on the cognitive, affective and social dimensions.

Results

Findings revealed significant group differences in how adolescents with CRPS described their imagined futures. Adolescents with CRPS used significantly fewer positive affect and more negative affect, anger and sadness words, and greater insight and discrepancy words. No significant groups differences were found for social words.

Conclusions

Substantial differences in cognitive and affective words were found between adolescents with and without CRPS. Findings provide novel insights into current understandings of cognitive, affective and social processes in adolescents living with chronic pain, particularly with regard to adolescent developmental trajectories, and may in turn highlight potential targets in psychosocial interventions for adolescents living with chronic pain.



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Homotopic reduction of laser evoked potential amplitude and laser‐pain rating by abdominal acupuncture

Abstract

Background

The neural mechanism underlying the analgesic effect of acupuncture is largely unknown. We aimed at investigating the effect of abdominal acupuncture (AA) on the laser evoked potential (LEP) amplitude and laser‐pain rating to stimulation of body parts either homotopic or heterotopic to the treated acupoint.

Methods

LEPs were recorded from 13 healthy subjects to stimulation of the right wrist (RW), left wrist (LW), and right foot (RF). LEPs were obtained before, during, and after the AA stimulation of an abdominal area corresponding to the representation of the right wrist. Subjective laser‐pain rating was collected after each LEP recording.

Results

The amplitude of the N2/P2 LEP component was significantly reduced during AA and 15 minutes after needle removal to both RW (F=4.14, p=0.02) and LW (F=5.48, p=0.008) stimulation, while the N2/P2 amplitude to RF stimulation (F=0.94, p=0.4) remained unchanged. Laser‐pain rating was reduced during AA and 15 minutes after needle removal only to RW stimulation (F=5.67, p=0.007).

Conclusion

Our findings showing an AA effect on LEP components to both the ipsilateral and contralateral region homotopic to the treated area, without any LEP change to stimulation of a heterotopic region, suggest that the AA analgesia is mediated by a segmental spinal mechanism.



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