Treatment with a carbon monoxide-releasing molecule (CORM-2) inhibits neuropathic pain and enhances opioid effectiveness in rats

Abstract Background Experiments were conducted to evaluate the contribution of P2X4 receptors to the modulation of neuropathy and their ability to amplify opioid effectiveness. Methods The study consisted of behavioral and biochemical analysis of the effect of a carbon monoxide donor – CORM-2, on the development of neuropathic pain in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Here, we exam if chronic intraperitoneal or intrathecal administration of CORM-2 influences CCI-induced allodynia and hyperalgesia. In parallel, changes of spinal microglial and/or astroglial activation were studied. CORM-2 was administered intrathecally [20 μg/5 μl] or intraperitoneally [10 mg/kg]. Results Here, we report that intraperitoneal or intrathecal chronic administration of the carbon monoxide donor CORM-2 significantly reduced the allodynia/hyperalgesia induced by CCI, with a parallel reduction of spinal microglial and/or astroglial activation. Furthermore, even a single intraperitoneal administration of CORM-2 had antiallodynic potency and moreover, increased morphine/buprenorphine analgesia compared to the effects of these drugs alone, completely eliminating the neuropathic pain symptoms. When CORM-2 was administered for 7 consecutive days, the antinociceptive effect of CORM-2 after CCI was stronger on day 7 than on day 2, which indicates that this effect built up over time. We are the first to demonstrate that even a single intraperitoneal injection of CORM-2 potentiates the antihyperalgesic and antiallodynic properties of morphine/buprenorphine in a CCI rat model. Conclusions Our data suggest that P2X4 receptors play a significant role in neuropathic pain development, suggesting that their blockade may have potential therapeutic utility.