European journal of pain : EJP
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P2X7 receptor antagonists have potential for treating various central nervous system (CNS) diseases, including neuropathic pain, although none have been approved for clinical use. Reasons may include insufficient understanding of P2X7 receptor signalling in pain, and the lack of a corresponding preclinical mechanistic biomarker. ⋯ Sub-optimal translation of preclinical molecules has hindered the clinical development of novel mechanism of action analgesics. We have undertaken a comprehensive in vitro analysis of migroglial signalling mechanisms recruited upon P2X7 receptor activation, a number of which were shown to be modulated by a selective P2X7 receptor antagonist in a well characterized animal model of neuropathic pain. Subject to further confirmation in other neuropathic models, this opens up the possibility to investigate their clinical utility as potential pain biomarkers in patients.
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Bladder pain syndrome/interstitial cystitis (BPS/IC) is a refractory disease accompanied by bladder-related pain and hyperactivity. Studies have shown that the translocator protein (TSPO) modulates neuroinflammation and central sensitisation associated with pain. Moreover, we previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates neuroinflammation and mechanical allodynia in cyclophosphamide (CYP)-induced cystitis through activation of glial cells. Here, we aimed to explore whether activation of TSPO attenuates mechanical allodynia and bladder dysfunction by regulating BDNF induced neuroinflammation in a CYP-induced cystitis model. ⋯ This study examined the mechanism underlying the ability of the translocator protein to modulate bladder pain syndrome/interstitial cystitis.
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Whereas previous studies revealed positive effects of emotional expressions such as swearing and laughing on acute pain, systematic research on the effects of crying on pain is missing. The rationale for the current study is that either a mere emotional distraction or changes in oxytocin and opioid levels represent a mechanism through which crying modulates pain, with the timing of mood changes as crucial information for distinguishing between potential mechanisms. ⋯ Despite previous findings on pain alleviating effects of emotional expression and the widespread idea about the generally beneficial consequences of emotional crying, research on the possible pain alleviating effects of crying is largely missing. Two quasi-experimental studies demonstrated that crying induced in laboratory conditions does not alleviate acute pain responses, suggesting that role of crying in pain interventions is doubtful. Less directly, results cast light on the role of emotional distraction from acute pain and possible crying-related neurochemical changes.