Analysis of interactions between serotonin and gabapentin or adenosine in the spinal cord of rats.
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.
Yoon
Myung Ha
MH
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr
Choi
Jeong Il
JI
Park
Heon Chang
HC
Bae
Hong Beom
HB
Jeong
Seong Wook
SW
Jeong
Chang Young
CY
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*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000241:Adenosine