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Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain.

Tissue injury induces a long-lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ-opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β-funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. In naïve or sham controls, systemic naloxone (3 mg/kg) produced conditioned place aversion, and systemic naltrexone (3 mg/kg) increased Fos expression in the central nucleus of the amygdala (CeA). In LS animals tested 3 weeks after plantar incision, systemic naltrexone reinstated mechanical hypersensitivity and produced an even greater increase in Fos than in sham controls, particularly in the capsular subdivision of the right CeA. One third of Fos+ profiles co-expressed protein kinase C delta (PKCδ), and 35% of PKCδ neurons co-expressed tdTomato+ in Oprm1 ::tdTomato transgenic mice. CeA microinjection of naltrexone (1 µg) reinstated mechanical hypersensitivity only in male mice and did not produce signs of somatic withdrawal. Intra-CeA injection of the MOR-selective inhibitor CTAP (300 ng) reinstated hypersensitivity in both male and female mice. We conclude that MORs in the capsular subdivision of the right CeA prevent the transition from acute to chronic postoperative pain.

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Mindfulness-Based Virtual Reality Intervention for Children and Young Adults with Inflammatory Bowel Disease: A Pilot Feasibility and Acceptability Study.

The aim of this pilot study was to assess: (1) the feasibility and acceptability of a Mindfulness-Based Virtual Reality (MBVR) intervention among children and young adults with Inflammatory Bowel Disease (IBD), and (2) the preliminary efficacy of MBVR on key psychological (anxiety) and physical (pain) outcomes. Participants were 62 children to young adults with IBD (M = 15.6 years; 69.4% Crohn's disease; 58% male) recruited from an outpatient pediatric IBD clinic. Participants completed a baseline assessment, underwent the 6-min MBVR intervention, completed a post-intervention assessment and study satisfaction survey, and provided qualitative feedback. Results suggest strong feasibility and acceptability. Participants reported high levels of satisfaction with MBVR including high levels of enjoyment (M = 4.38; range 1-5) and relaxation (M = 4.35; range 1-5). Qualitative data revealed several key themes including participants interest in using MBVR in IBD medical settings (e.g., hospitalizations, IBD procedures, IBD treatments), as well as in their daily lives to support stress and symptom management. Preliminary analyses demonstrated improvements in anxiety ( = 4.79, = 0.001) and pain ( = 3.72, < 0.001) following MBVR. These findings provide initial support for the feasibility and acceptability of MBVR among children and young adults with IBD. Results also suggest MBVR may improve key IBD outcomes (e.g., anxiety, pain) and highlight the importance of conducting a randomized controlled trial and more rigorous research to determine intervention efficacy.

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The efficacy of an educational movie to improve pain and dysfunctional behavior in school children: A randomized controlled trial.

Chronic pain in children is a serious issue, therefore calling for effective prevention/intervention measures. This study aimed to evaluate the efficacy of an educational movie on pain knowledge in school children in general and on pain-related behaviours and pain intensity in those who are affected by chronic pain. Regarding those affected, the association between pain knowledge and intensity, as well as the potential mediating effect of pain-related behaviours, were investigated.

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The tunicate metabolite 2-(3,5-diiodo-4-methoxyphenyl)ethan-1-amine targets ion channels of vertebrate sensory neurons.

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Sex Differences, Sleep Disturbance and Risk of Persistent Pain Associated With Groin Hernia Surgery: A Nationwide Register-Based Cohort Study.

Persistent pain after groin hernia repair is a major health problem. Sleep disturbance is associated with heightened pain sensitivity. The main objective of this study was to examine the role of sleep disturbance in the development and long-term maintenance of chronic postherniorrhaphy inguinal pain (CPIP), with exploration of sex differences. From 2012-2017, a national cohort of patients with prior groin hernia repair (n=2084;45.8% females) were assessed for the development of CPIP 12 months after surgery. Patients then underwent long-term (median 5.0 years) follow-up to evaluate the contribution of sex and sleep disturbance on the maintenance of CPIP. Associations between pre- and postoperative sleep problems (assessed at long-term follow-up) and CPIP were tested using logistic regression. Females had higher rates of CPIP with negative impact on daily activities 12 months after surgery as compared to males (14.6 vs 9.2%,p<0.0005), and were more likely to have moderate-severe CPIP in the long-term (3.1 vs 1.2%,p=0.003). Preoperative sleep problems predicted development of CPIP 12 months after surgery (adjusted odds ratio (aOR) 1.76 (95%CI 1.26-2.46),p=0.001) and CPIP in the long-term (aOR 2.20 (1.61-3.00),p<0.0001). CPIP was associated with insomnia and depression. Sleep disturbance may increase the risk for CPIP, and contribute to maintenance of postsurgical pain. PERSPECTIVE: Females are at heightened risk for CPIP as compared to males. Increased severity of pain symptoms are linked to poorer sleep and psychiatric morbidity. Given the robust associations between sleep disturbance and CPIP, interventions which consolidate and promote sleep, especially in females, may improve long-term pain control.

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Validation of the Bath CRPS Body Perception Disturbance Scale.

The Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") measures alterations in body perception. We assessed its internal consistency, known group validity, construct validity, and associations with demographic and clinical characteristics. We also evaluated changes in, and baseline predictors of B-CRPS-BPDS scores at follow-up. We included people with CRPS (N=114) and pain-free controls (N=69). People with CRPS obtained higher scores than pain-free controls on all B-CRPS-BPDS items, except the item on attention. Because this item also had an insufficient corrected item-total correlation, we propose a revised B-CRPS-BPDS (r-B-CRPS-BPDS) excluding this item. The internal consistency of the r-B-CRPS-BPDS was good. The r-B-CRPS-BPDS showed a large positive relationship with "motor neglect-like symptoms", indicating good construct validity. The r-B-CRPS-BPDS showed positive relationships with pain intensity, fear of movement, depression, and upper limb disability. There were no independent relationships with handedness, affected side, affected limb, disease duration, CRPS severity score, tension, anger, fatigue, confusion, and vigour. Finally, r-B-CRPS-BPDS scores did not consistently change over time. Our results demonstrate the utility of the r-B-CRPS-BPDS for measuring body perception disturbances in CRPS. Perspective: This article evaluates the validity of the Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") in CRPS, and assesses relationships with demographic and clinical variables. The proposed revised B-CRPS-BPDS appears to be a valid measure of body perception disturbances in CRPS.

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fMRI findings in MTBI patients with headaches following rTMS.

Mild Traumatic Brain Injury (MTBI) patients with persistent headaches are known to have diminished supraspinal modulatory connectivity from their prefrontal cortices. Repetitive transcranial magnetic stimulation (rTMS) is able to alleviate MTBI-related headache (MTBI-HA). This functional magnetic resonance imaging (fMRI) study assessed supraspinal correlates associated with the headache analgesic effect of rTMS at left prefrontal cortex (LPFC), hypothesizing real rTMS would significantly increase modulatory functions at LPFC in comparison to sham treatment. Subjects with MTBI-HA were randomized to receive either real or sham rTMS treatments and subjected to pre- and post-treatment resting state and evoked heat-pain fMRI as described in a prior study. Real rTMS consisted of 2000 pulses delivered at 10 Hz and 80% of the resting motor threshold at left dorsolateral prefrontal cortex, whereas sham treatment was delivered with same figure-of-eight coil turned 180 degrees. Follow-up fMRI was performed one-week post-treatment. All fMRI data was processed using BrainVoyager QX Software. 14 subjects receiving real and 12 subjects receiving sham treatments completed the study. The REAL group demonstrated significant (P < 0.02) decreases in headache frequency and intensity at one week following treatment. fMRI scans in the REAL group showed increased evoked heat pain activity (P < 0.002) and resting functional connectivity (P < 0.0001) at the LPFC after rTMS. Neither this significant analgesic effect nor these fMRI findings were seen in the sham group. Sham treatment was, however, associated with a decrease in resting state activity at the LPFC (P < 0.0001). This study correlates the demonstrated analgesic effect of rTMS in the treatment of MTBI-HA with enhanced supraspinal functional connectivity in the left prefrontal cortex, which is known to be involved in "top-down" pain inhibition along the descending midbrain-thalamic-cingulate pathway. Trial Registration: This study was registered on September 24, 2013, on ClinicalTrials.gov with the identifier: NCT01948947. https://clinicaltrials.gov/ct2/show/NCT01948947 .

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Cohort profile: DOLORisk Dundee: a longitudinal study of chronic neuropathic pain.

Neuropathic pain is a common disorder of the somatosensory system that affects 7%-10% of the general population. The disorder places a large social and economic burden on patients as well as healthcare services. However, not everyone with a relevant underlying aetiology develops corresponding pain. DOLORisk Dundee, a European Union-funded cohort, part of the multicentre DOLORisk consortium, was set up to increase current understanding of this variation in onset. In particular, the cohort will allow exploration of psychosocial, clinical and genetic predictors of neuropathic pain onset.

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Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis.

Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics.

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Human cells and networks of pain: Transforming pain target identification and therapeutic development.

Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this challenge.

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