Mol Pain
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Background Chronic pain affects millions of people worldwide; however, its cellular and molecular mechanisms have not been completely elucidated. It is thought that chronic pain is triggered by nociceptive sensitization, which produces elevated nocifensive responses. A model has been developed in Drosophila melanogaster to investigate the underlying mechanisms of chronic pain using ultraviolet-induced tissue injury to trigger thermal allodynia, a nociceptive hypersensitivity to a normally innocuous stimulus. ⋯ The effects on pain perception appear to be specific to the sensitization system, as the ability to respond to a normally noxious stimulus in the absence of injury was left intact, and no nociceptor morphological defects were observed. Conclusion These results provide further support of the hypothesis that the BMP pathway plays a crucial role in the development of nociceptive sensitization. Because of its strong conservation between invertebrates and mammals, the BMP pathway may be worthy of future investigation for the development of targeted treatments to alleviate chronic pain.
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Background Offset analgesia is a disproportionate decrease of pain perception following a slight decrease of noxious thermal stimulus and attenuated in patients with neuropathic pain. We examined offset analgesia in patients with heterogeneous chronic pain disorders and used functional magnetic resonance imaging to explore modification of cerebral analgesic responses in comparison with healthy controls. Results We recruited seventeen patients with chronic pain and seventeen age-, sex-matched healthy controls. ⋯ The present findings might implicate both behavioral and cerebral plastic alterations contributing to chronification of pain. Clinical trial registry: The Japanese clinical trials registry (UMIN-CTR, No. UMIN000011253; http://www.umin.ac.jp/ctr /).
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Vortioxetine is a multimodal antidepressant that potently antagonizes 5-HT3 serotonin receptors, inhibits the high-affinity serotonin transporter, activates 5-HT1A and 5-HT1B receptors, and antagonizes 5-HT1D and 5-HT7 receptors. 5-HT3 receptors largely mediate the hyperalgesic activity of serotonin that occurs in response to nerve injury. Activation of 5-HT3 receptors contributes to explain why selective serotonin reuptake inhibitors, such as fluoxetine, are not indicated in the treatment of neuropathic pain. Here, we studied the analgesic action of vortioxetine in the chronic constriction injury model of neuropathic pain in mice. ⋯ Vortioxetine enhanced mechanical pain thresholds in chronic constriction injury mice without changing motor activity, as assessed by the open-field and horizontal bar tests. None of the three antidepressants caused analgesia in the complete Freund's adjuvant model of chronic inflammatory pain. These findings raise the attractive possibility that vortioxetine can be effective in the treatment of neuropathic pain, particularly in patients with comorbid depression and cognitive dysfunction.
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Background The aim of this study was to assess peripheral measures and central metabolites associated with lipids using magnetic resonance spectroscopy. Results Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy controls participated. Using magnetic resonance spectroscopy, we measured the levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine (tCr) levels in the right and left thalamus. ⋯ On the other hand, there were positive correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients. There were significant correlations between Lip13a/tCr or Lip09/tCr and different peripheral measures depending on the side of the thalamus (right or left) in CRPS patients. Conclusion This is the first report indicating that abnormal interactions of Lip13a and Lip09 in the thalamus with peripheral measures and central metabolites may mediate the complex pathophysiological mechanisms underlying CRPS.
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Objective To investigate brain morphometric changes in medication-overuse headache with excessive intake of caffeine-containing combination analgesics. Materials and methods We recruited 32 medication-overuse headache patients overusing caffeine-containing combination analgesics and 26 normal controls with matched sex and age. Magnetic resonance T1-weighted images were processed by automatic volume algorithm of brain regions over the whole brain according to the neuromorphometrics template. ⋯ In regression analyses, the volume of bilateral middle occipital gyrus had negative association with migraine duration, and the volume of right lateral orbital gyrus and right superior parietal lobe was negatively correlated with number of medications per month. Conclusions Volume changes of brain regions involved in affective and cognitive processing, visual and auditory perception, and pain sensory/discrimination suggested a particular role of those regions in the pathogenesis of medication-overuse headache overusing caffeine-containing combination analgesics. Morphometric changes in multiple visual processing areas and volume gain in lower headache frequency and less anxiety and depression may be specific features related to overusing caffeine-containing combination analgesics.