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Sex differences and the role of ovarian hormones in site-specific nociception of SHR rats.

The accurate diagnosis and treatment of pain is dependent upon the knowledge of variables that might alter this response. Some of these variables are the locality of the noxious stimulus, the sex of the individual, and the presence of chronic diseases. Among these chronic diseases, hypertension is considered a serious and silent disease that has been associated with hypoalgesia. The main goal of this study was to evaluate the potential nociceptive differences in spontaneously hypertensive rats (SHR) regarding the locality of the stimulus, the temporomandibular joint or paw, the sex, and the role of ovarian hormones in a model of mechanical nociception (Von Frey test) or formalin-induced inflammatory nociception. Our results indicate that SHR has lower orofacial mechanical nociception beyond the lower mechanical nociception in the paw compared to WKY rats. In a model of formalin-induced inflammatory nociception, SHR also has a decreased nociception compared to normotensive rats. We also sought to evaluate the influence of sex and ovarian hormones on orofacial mechanical nociception in SHR. We observed that female SHR has higher mechanical nociception than male SHR only in the paw, but it has higher formalin-induced orofacial nociception than male SHR. Moreover, the absence of ovarian hormones caused an increase in mean arterial pressure and a decrease in paw nociception in female SHR.

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Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome.

Little is known about the link between pathophysiologic factors and symptoms of irritable bowel syndrome (IBS), or whether these factors have cumulative effects on patient-reported outcomes (PROs). We investigated whether pathophysiologic alterations associated with IBS have cumulative or independent effects on PROs.

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Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study.

Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes.

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Do β-adrenoreceptor blocking drugs associate with reduced risk of symptomatic osteoarthritis and total joint replacement in the general population? A primary care-based, prospective cohort study using the Clinical Practice Research Datalink.

To investigate if β-adrenoreceptor blocking drug (β-blocker) prescription reduces the risk of knee or hip osteoarthritis, total joint replacement and analgesic prescription.

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Efficacy of a transdiagnostic emotion-focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial.

The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion-focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion-focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.

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Deep brain stimulation of chronic cluster headaches: Posterior hypothalamus, ventral tegmentum and beyond.

We present long-term follow-up results and analysis of stimulation sites of a prospective cohort study of six patients with chronic cluster headaches undergoing deep brain stimulation of the ipsilateral posterior hypothalamic region.

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Sensory, Affective, and Catastrophizing Reactions to Multiple Stimulus Modalities: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP).

Native Americans (NAs) have a higher prevalence of chronic pain than any other U.S. racial/ethnic group; however, little is known about the mechanisms for this pain disparity. This study used quantitative sensory testing (QST) to assess pain experience in healthy, pain-free adults (N=137 NAs [87 female], N=145 non-Hispanic whites [NHW; 68 female]) following painful electric, heat, cold, ischemic, and pressure stimuli. Following each stimulus, ratings of pain intensity, sensory pain, affective pain, pain-related anxiety, and situation-specific pain catastrophizing were assessed. Results suggested that NAs reported greater sensory pain in response to suprathreshold electric and heat stimuli, greater pain-related anxiety to heat and ischemic stimuli, and more catastrophic thoughts in response to electric and heat stimuli. Sex differences were also noted; however, with the exception of catastrophic thoughts to cold, these were not moderated by race/ethnicity. Together, findings suggest NAs experience heightened sensory, anxiety, and catastrophizing reactions to painful stimuli. This could place NAs at risk for future chronic pain and could ultimately lead to a vicious cycle that maintains pain (e.g., pain→anxiety/catastrophizing→pain). PERSPECTIVE: Native Americans experienced heightened sensory, anxiety, and catastrophizing reactions in response to multiple pain stimuli. Given the potential for anxiety and catastrophic thoughts to amplify pain, this may place them at risk for pain disorders and could lead to a vicious cycle that maintains pain.

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Reward for pain. Hyperalgesia and allodynia induced by operant conditioning: systematic review and meta-analysis.

Learning processes have been discussed in the context of pain chronicity for decades. Particularly, operant conditioning has been used to experimentally induce and modulate pain in healthy humans. In this systematic review and meta-analysis, research findings on pain facilitation (hyperalgesic effect) and pain elicitation (allodynic effect) are evaluated. The review was performed according to the PRISMA guideline and an a priori published protocol. Nine databases were searched for relevant publications: PubMed, Cochrane Register of Controlled Trials (CENTRAL), Web of Science™, ScienceDirect, EBSCO, PsycINFO, MEDLINE, PsycARTICLES and CINAHL. Studies were included if they investigated pain-free humans, exposed to an operant conditioning procedure of pain. Two independent assessors screened publications against eligibility criteria and assessed the risk of bias (RoB) with the Cochrane RoB scale. A total of 3155 records were screened of which 8 were included into the qualitative (401 participants) and 5 into the quantitative (110 participants) synthesis. Results showed that hyperalgesic (standardized mean difference [SMD] of -0.80, 95% CI: -1.33 to -0.27, p = 0.003) and allodynic effects (-1.27, 95% CI: -2.46 to -0.08, p = 0.04) can be induced in healthy humans, indicating that pain can be shaped by contingencies of reinforcement. However, the uncertainty of the effect is relatively high, mostly due to the small number of included studies, demand characteristics and the risk of bias. This is especially relevant for studies on allodynic effects where the decrease in nociception should be more rigorously controlled. PERSPECTIVE: Operant conditioning can be a mechanism of pain chronicity. All experimental studies investigating this hypothesis have been identified and summarized. It has been demonstrated that allodynic and hyperalgesic effects can be induced by operant conditioning.

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Mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn.

The long-term use of opioid analgesics is limited by the development of unwanted side-effects, such as tolerance. The molecular mechanisms of morphine anti-nociceptive tolerance are still unclear. The mitochondrial calcium uniporter (MCU) is involved in painful hyperalgesia, but the role of MCU in morphine tolerance has not been uncharacterised.

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Migraine and the trigeminovascular system-40 years and counting.

The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role for the neuropeptide-containing trigeminal nerve. This hypothesis led to a transformation in the migraine field and understanding of key concepts surrounding migraine, including the role of neuropeptides and their release from meningeal trigeminal nerve endings in the mechanism of migraine, blockade of neuropeptide release by anti-migraine drugs, and activation and sensitisation of trigeminal afferents by meningeal inflammatory stimuli and upstream role of intense brain activity. The study of neuropeptides provided the first evidence that antisera directed against calcitonin gene-related peptide (CGRP) and substance P could neutralise their actions. Successful therapeutic strategies using humanised monoclonal antibodies directed against CGRP and its receptor followed from these findings. Nowadays, 40 years after the initial proposal, the trigeminovascular system is widely accepted as having a fundamental role in this highly complex neurological disorder and provides a road map for future migraine therapies.

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