title: Analysis of interactions between serotonin and gabapentin or adenosine in the spinal cord of rats.
abstract: We evaluated the nature of the pharmacologic interaction after concurrent administration of 5-HT-gabapentin and 5-HT-adenosine at the spinal level. Intrathecal catheters were placed in the subarachnoid space of male Sprague-Dawley rats. Nociception was induced by subcutaneous injection of formalin solution (5%, 50 microl) into the hind paw. A fixed dose analysis and an isobolographic analysis were used to determine the properties of interaction. Intrathecal 5-HT dose-dependently suppressed the flinching response during phase 1 of the formalin test, while neither gabapentin nor adenosine affected the phase-1 flinching response. All three intrathecal drugs attenuated the phase-2 flinching response in a dose-dependent manner. The intrathecal combination of 5-HT with a fixed dose of gabapentin or adenosine in phase 1 had little effect or increased the antinociception of 5-HT alone. Isobolographic analysis in phase 2 revealed an additive or a synergistic interaction after intrathecal delivery of 5-HT-gabapentin or 5-HT-adenosine mixture. Taken together, the combination of 5-HT with either gabapentin or adenosine may offer a potential remedy in the treatment of the facilitated state as well as acute pain in the spinal cord.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.forename: Heon Chang
authors.initials: HC
authors.lastname: Park
authors.forename: Hong Beom
authors.initials: HB
authors.lastname: Bae
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Jeong
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Jeong
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000077206:Gabapentin; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000241:Adenosine