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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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome.
Learn More >Many of those aging with HIV suffer from distal neuropathic pain (DNP) due to HIV-associated sensory neuropathy (HIV-SN). Prior studies have linked chronic pain conditions to a variant of the catechol-O-methyltransferase (COMT), ValMet. This variant confers reduced enzymatic activity and results in higher synaptic dopamine levels. Here we examined the role of ValMet as a predictor of DNP in HIV-SN.
Learn More >Prehabilitation programs have led to improved postoperative outcomes in several surgical contexts, but there are presently no guidelines for the prehabilitation phase before lumbar fusion surgery.
Learn More >Pain is reported to affect over 70% of individuals with inflammatory bowel diseases (IBD), with abdominal and musculoskeletal (MSK) pain representing the most common complaints. MSK pain is typically considered within the narrow framework of inflammatory extraintestinal manifestations of IBD, resulting in a limited scope for the nature and underlying mechanisms participating in MSK pain experiences in this population. Symptoms related to central sensitization have recently demonstrated association with active IBD and worse MSK pain experiences, suggesting a potential roll for central mechanisms in MSK-related pain. Current literature exploring persistent pain in chronic inflammatory and MSK populations propose complex pain models comprised of dynamic nervous system relationships influenced by primary disease features and concomitant pain states, as well as affective and cognitive components. Nervous system contributions in the development and maintenance of persistent pain are postulated to include mechanisms of peripheral and central sensitization, changes in descending central modulation, as well as structural brain changes. These models go beyond current MSK pain models described in IBD literature, highlighting the need for new frameworks for considering MSK-related pain in IBD. Consequently, this paper proposes a broader theoretical model whereby central mechanisms, such as central sensitization and grey matter changes, as well as psychological and disease factors are suggested to modulate pain experiences in this population. Exploration of relationships within the proposed framework may provide not only a deeper understanding of the generation and maintenance of persistent MSK pain in IBD, but also highlight the need for new targeted management pathways in this population. This paper hypothesizes that exploration of central sensitization in IBD patients will demonstrate altered somatosensory functioning in patients with MSK pain, and that IBD activity and psychological factors will be associated with altered somatosensory functioning and worse pain experiences.
Learn More >We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.
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