Agnieszka M Jurga1, Anna Piotrowska2, Joanna Starnowska3, Ewelina Rojewska4, Wioletta Makuch5, Joanna Mika6. 1. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: jurga@if-pan.krakow.pl. 2. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: ania.piotrowska@uj.edu.pl. 3. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: joanna.starnowska@gmail.com. 4. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: rojewska@if-pan.krakow.pl. 5. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: makuch@if-pan.krakow.pl. 6. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: joasia272@onet.eu.
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 [20μg/5μl] or intraperitoneally [10mg/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.
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 monoxidedonor - 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 [20μg/5μl] or intraperitoneally [10mg/kg]. RESULTS: Here, we report that intraperitoneal or intrathecal chronic administration of the carbon monoxidedonor 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 CCIrat 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.
Authors: Agnieszka M Jurga; Anna Piotrowska; Wioletta Makuch; Barbara Przewlocka; Joanna Mika Journal: Front Pharmacol Date: 2017-02-16 Impact factor: 5.810