Pain
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Chronic pain syndromes (CPS) are highly prevalent in the general population, and increasingly the evidence points to a common etiological pathway. Using a large cohort of twins (n=8564) characterized for chronic widespread musculoskeletal pain (CWP), chronic pelvic pain (PP), migraine (MIG), dry eye disease, and irritable bowel syndrome (IBS), we explored the underlying genetic and environmental factors contributing to CPS and the correlation between them. The sample was predominantly female (87.3%), with a mean age of 54.7 (±14.7) years. ⋯ Excluding MIG from further analyses, cross-twin cross-trait correlations were higher in monozygotic compared with dizygotic twin pairs, suggestive of shared genetic factors between CWP, PP, IBS, and dry eye disease. Twin modeling analysis revealed the common pathway model as the model best explaining the observed pattern of correlation between the traits, with an estimated heritability of 66% of the underlying latent variable. These results are evidence of shared genetic factors in conditions manifesting chronic pain and justify the search for underlying genetic variants.
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Case Reports
Hemibody pain relieved by microvascular decompression of the contralateral caudal medulla Case Report.
Microvascular decompression (MVD) of cranial nerves has become an established treatment for trigeminal and (vago)glossopharyngeal neuralgia and for hemifacial spasm. The authors present the case of a 64-year-old man who had a 3.5-year history of severe, drug-resistant hemibody pain with sensory and autonomic disturbance. The ipsilateral trigeminal, cochlear, and glossopharyngeal function also was affected. ⋯ After MVD of the medulla, there was an immediate and complete resolution of the pain and almost complete resolution of the sensory and autonomic disturbances. The pain later recurred mildly and transiently. The residual symptoms had resolved by 2 years.
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Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain. Data were used on 1632 subjects of the Netherlands Study of Depression and Anxiety. ⋯ For some LPS-stimulated inflammatory markers, we did find elevated levels in subjects with chronic multisite musculoskeletal pain both before and after adjustment for covariates. Pain severity was not associated with inflammation within chronic pain subjects. An enhanced innate immune response in chronic multisite musculoskeletal pain may be examined as a potential biomarker for the onset or perpetuation of chronic pain.
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Mas-related G-protein-coupled receptor subtype C (mouse MrgC11 and rat rMrgC), expressed specifically in small-diameter primary sensory neurons, may constitute a novel pain inhibitory mechanism. We have shown previously that intrathecal administration of MrgC-selective agonists can strongly attenuate persistent pain in various animal models. However, the underlying mechanisms for MrgC agonist-induced analgesia remain elusive. ⋯ These findings indicate that activation of endogenously expressed MrgC receptors at central terminals of primary sensory fibers may decrease peripheral excitatory inputs onto SG neurons. Together, these results suggest potential cellular and molecular mechanisms that may contribute to intrathecal MrgC agonist-induced analgesia. Because MrgC shares substantial genetic homogeneity with human MrgX1, our findings may suggest a rationale for developing intrathecally delivered MrgX1 receptor agonists to treat pathological pain in humans and provide critical insight regarding potential mechanisms that may underlie its analgesic effects.