Neuropathic pain is primarily caused by nervous system lesions or dysfunction. Evidence strongly suggests that obesity, diabetes and cancer are common in chronic pain conditions, and pain complaints are common in these individuals. Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal models Mouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively.Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (Von Frey test) tests at baseline and 30, 60, 120 and 180 minutes after asprosin administration. Serum level of asprosin was quanti ed by ELISA.In all three neuropathic pain models (STZ, OXA and CCI), asprosin administration signi cantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. Asprosin levels were signi cantly lower in three types of neuropathic pain compare to controls (p < 0.05).The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.
Agomelatine, a novel antidepressant exerting its effects through melatonergic and serotonergic systems, implicated to be effective against pain including neuropathic pain but without any knowledge of mechanism of action. To explore the possible role of agomelatine on nociceptive transmission at the peripheral level, the effects of agomelatine on intracellular calcium ([Ca2+]i) signaling in peripheral neurons were investigated in cultured rat dorsal root ganglion (DRG) neurons. Using the fura‐2‐based calcium imaging technique, the effects of agomelatine on [Ca2+]i and roles of the second messenger‐mediated pathways were assessed. Agomelatine caused [Ca2+]i signaling in a dose‐dependent manner when tested at 10 and 100 μM concentration. Luzindole, a selective melatonin receptor antagonist, almost completely blocked the agomelatine‐induced calcium signals. The agomelatine‐induced calcium transients were also nearly abolished following pretreatment with the 100 ng/ml pertussis toxin, a Gi/o protein inhibitor. The stimulatory effects of agomelatine on [Ca2+]i transients were significantly reduced by applications of phospholipase C (PLC) and protein kinase C (PKC) blockers, 10 μM U73122, and 10 μM chelerythrine chloride, respectively. The obtained results of agomelatine‐induced [Ca2+]i signals indicates that peripheral mechanisms are involved in analgesic effects of agomelatine. These mechanisms seems to involve G‐protein‐coupled receptor activation and PLC and PKC mediated mechanisms.
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