Hossein Ali Safakhah1,2, Farkhondeh Damghanian1,2, Ahmad-Reza Bandegi3, Hossein Miladi-Gorji4,5. 1. Laboratory of Animal Addiction Models, Research Center of Physiology, School of Medicine, Semnan University of Medical Sciences, P.O. Box 35131-38111, Semnan, Iran. 2. Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 3. Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 4. Laboratory of Animal Addiction Models, Research Center of Physiology, School of Medicine, Semnan University of Medical Sciences, P.O. Box 35131-38111, Semnan, Iran. Miladi331@yahoo.com. 5. Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Miladi331@yahoo.com.
Abstract
BACKGROUND: Chronic use of morphine treatment for neuropathic pain leads to morphine-induced analgesic tolerance. Crocin contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. This study examined the effects of crocin on morphine tolerance and serum BDNF levels on neuropathic pain induced by chronic constriction injury (CCI) in rats. METHODS: CCI model of neuropathic pain was done in male Wistar rats (200-250 g). Rats were treated with crocin (15 or 30 mg/kg, intraperitoneally) alone or simultaneously with morphine (10 mg/kg, subcutaneously) during or after induction of CCI. Pain behavioral responses including mechanical allodynia and thermal hyperalgesia were measured from days of 15-27 after CCI. Then, rats were evaluated for serum BDNF levels on days 14 and/or 27. RESULTS: We found that morphine tolerance developed after the induction of neuropathic pain. The injection of crocin (15 and 30 mg/kg) was able to enhance analgesic effect of morphine by reduction of mechanical allodynia on days 15-27 post-surgery in CCI rats. While preemptive administration of crocin at a lower dose (15 mg/kg) maintained the analgesic effect of morphine. Morphine injection and/or co-administration with crocin (15, 30 mg/kg) decreased serum BDNF levels in CCI rats. CONCLUSION: These findings indicate that crocin may have a therapeutic effect to maintain morphine analgesic efficacy and also to prevent the development of morphine tolerance in neuropathic pain, but probably not through BDNF.
BACKGROUND: Chronic use of morphine treatment for neuropathic pain leads to morphine-induced analgesic tolerance. Crocin contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. This study examined the effects of crocin on morphine tolerance and serum BDNF levels on neuropathic pain induced by chronic constriction injury (CCI) in rats. METHODS:CCI model of neuropathic pain was done in male Wistar rats (200-250 g). Rats were treated with crocin (15 or 30 mg/kg, intraperitoneally) alone or simultaneously with morphine (10 mg/kg, subcutaneously) during or after induction of CCI. Pain behavioral responses including mechanical allodynia and thermal hyperalgesia were measured from days of 15-27 after CCI. Then, rats were evaluated for serum BDNF levels on days 14 and/or 27. RESULTS: We found that morphine tolerance developed after the induction of neuropathic pain. The injection of crocin (15 and 30 mg/kg) was able to enhance analgesic effect of morphine by reduction of mechanical allodynia on days 15-27 post-surgery in CCIrats. While preemptive administration of crocin at a lower dose (15 mg/kg) maintained the analgesic effect of morphine. Morphine injection and/or co-administration with crocin (15, 30 mg/kg) decreased serum BDNF levels in CCIrats. CONCLUSION: These findings indicate that crocin may have a therapeutic effect to maintain morphine analgesic efficacy and also to prevent the development of morphine tolerance in neuropathic pain, but probably not through BDNF.
Authors: Abbas Ali Vafaei; Hossein Ali Safakhah; Simin Jafari; Azin Tavasoli; Ali Rashidy-Pour; Ali Ghanbari; Seyed Ali Seyedinia; Parnia Tarahomi Journal: J Exp Pharmacol Date: 2020-04-28