title: Morphine can enhance the antiallodynic effect of intrathecal R-PIA in rats with nerve ligation injury.
abstract: Nerve ligation injury may produce a tactile allodynia. Intrathecal adenosine receptor agonists or morphine have an antiallodynic effect. In this study, we examined the effect of intrathecal morphine on the antiallodynic state induced by the adenosine A1 receptor agonist, N(6)-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA), in a rat model of nerve ligation injury. Rats were prepared with ligation of left L5-6 spinal nerves and intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments to the lesioned hindpaw. Thresholds for withdrawal response were assessed. Morphine and R-PIA were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50)s were administered concurrently to establish the ED(50) of the drug combination. The drug interaction was analyzed using the isobolographic method. Intrathecal 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1 receptor antagonist, and naloxone were administered to examine the reversal of the antiallodynic effect. Side effects were also observed. Intrathecal morphine and R-PIA and their combination produced a dose-dependent antagonism without severe side effects. Intrathecal morphine synergistically enhanced the antiallodynic effect of R-PIA when coadministered. Intrathecal naloxone and DPCPX reversed the maximal antiallodynic effect in the combination group. These results suggest that activation of mu-opioid and A1 receptors at the spinal level is required for the synergistic interaction on tactile allodynia.
authors.affiliation: Department of Anesthesia and Pain Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Jai-Hyun
authors.initials: JH
authors.lastname: Hwang
authors.forename: Gyu-Sam
authors.initials: GS
authors.lastname: Hwang
authors.forename: Sung-Kang
authors.initials: SK
authors.lastname: Cho
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Han
mesh_terms: D058907:Adenosine A1 Receptor Agonists; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010660:Phenylisopropyladenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000627:therapeutic use
chemical_list: D058907:Adenosine A1 Receptor Agonists; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D014970:Xanthines; D010660:Phenylisopropyladenosine; D009270:Naloxone; D009020:Morphine; C051360:1,3-dipropyl-8-cyclopentylxanthine