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Alterations in cellular energy metabolism have been implicated in chronic pain suggesting a role for mitochondrial DNA (mtDNA). Previous studies reported associations of a limited number of mtDNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions. A discovery cohort consisting of 609 participants either with or without a complex persistent pain conditions (CPPC) was examined. mtDNA was subjected to deep sequencing for identification of rare mutations, common variants, haplogroups, and heteroplasmy associated with five CPPCs: episodic migraine, irritable bowel syndrome, fibromyalgia, vulvar vestibulitis, or temporomandibular disorders. The strongest association found was the presence of the C allele at the single nucleotide polymorphism (SNP) m.2352T>C (rs28358579) that significantly increased the risk for fibromyalgia (OR=4.6, P=4.3×10). This relationship was even stronger in women (OR=5.1, P=2.8×10), and m.2352T>C was associated with all other CPPCs in a consistent risk-increasing fashion. This finding was replicated in another cohort (OR=4.3, P=2.6×10) of the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study consisting of 1754 female participants. To gain insight into the cellular consequences of the associated genetic variability, we conducted an assay testing metabolic reprogramming in human cell lines with defined genotypes. The minor allele C was associated with decreased mitochondrial membrane potential under conditions where oxidative phosphorylation is required, indicating a role of oxidative phosphorylation in pathophysiology of chronic pain. Our results suggest that cellular energy metabolism, modulated by m.2352T>C, contributes to fibromyalgia and possibly other chronic pain conditions.
Learn More >To evaluate the influence of self-reported physical activity and sleep quality on conditioned pain modulation (CPM) in the orofacial region.
Learn More >Chronic pain is one of the most common and challenging symptoms in fibromyalgia (FM). Currently, self-reported pain is the main criterion used by clinicians assessing patients with pain. However, it is subjective, and multiple factors can affect pain levels. In this study, we investigated the neural correlates of FM pain using conditioned pain modulation (CPM), electroencephalography (EEG), and transcranial magnetic stimulation (TMS).
Learn More >Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis.
Learn More >The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects.
Learn More >Remote electrical neuromodulation (REN) is a novel acute treatment of migraine. Upper arm peripheral nerves are stimulated to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. The REN device (Nerivio, Theranica Bio-Electronics LTD., Israel) is FDA-authorized for acute treatment of migraine in adults who do not have chronic migraine. The current study assessed the consistency of response over multiple migraine attacks in people with chronic migraine who are typically characterized with severe pain intensity, high disability, and less robust response to triptans.
Learn More >Chronic Post Traumatic Headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic non-traumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of the present study was to investigate whether circulating oxylipins measured in the acute setting following TBI, could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days post-injury with a neurobehavioral symptom inventory (NSI) and satisfaction with-life-survey (SWLS). Liquid chromatography tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosaheaxaenoic acid (DHA), and n-6 arachidonic acid (AA) and linoleic acid (LA).Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or SWLS scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (an LA derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.
Learn More >Tapentadol is a dual-acting mu-opioid receptor agonist and noradrenaline reuptake inhibitor with non-inferior analgesic efficacy to oxycodone and better gastrointestinal tolerability than full mu-opioid receptor agonists. Tapentadol is approved for cancer pain in Japan; however, real-world evidence on tapentadol's effectiveness and safety for cancer-related pain in Japan is limited.
Learn More >Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis.
Learn More >Pain is one of the most common symptoms that people with cancer experience. Identification of demographic, physiologic, and behavioral correlates of pain among cancer survivors could help identify subgroups most in need of pain management.
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