Mol Pain
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Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of μ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition. ⋯ We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system.
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Koumine is an alkaloid monomer found abundantly in Gelsemium plants. It has been shown to reverse thermal hyperalgesia and mechanical allodynia induced by sciatic nerve chronic constriction injury (CCI) in rats in a dose-dependent manner. Interestingly, this effect is mediated by elevated allopregnanolone levels in the spinal cord (SC). Since 3α-hydroxysteroid oxidoreductase (3α-HSOR), the key synthetase of allopregnanolone, is responsible for allopregnanolone upregulation in the SC, the objective of the present study was to investigate the role of its expression in the SC in koumine-induced analgesia using a rat model of neuropathic pain following peripheral nerve injury. ⋯ This study demonstrates that 3α-HSOR is an important molecular target of koumine for alleviating neuropathic pain. Koumine may prove a promising compound for the development of novel analgesic agents effective against intractable neuropathic pain.