Dual effect of serotonin on formalin-induced nociception in the rat spinal cord.
To examine the role of the descending serotonergic system in the regulation of spinal nociceptive processing, the effects of serotonin (5-HT) and selective ligands for 5-HT receptor subtypes on persistent nociception were investigated. Formalin (5% formaldehyde) injected into the plantar region of the rat hindpaw induced two phases of aversive responses such as licking and biting. Intrathecal administration of selective 5-HT3 receptor antagonists, granisetron (0.1-100 pmol/rat) and ondansetron (1-1000 pmol/rat), reduced the second phase of the formalin-induced aversive responses without affecting the first one. The antinociceptive effect of granisetron (100 pmol/rat) was abolished when 5-HT was depleted from the lumbar cord by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT). In the 5,7-DHT-treated rats, intrathecal administration of 1-(m-chlorophenyl)-biguanide, a selective 5-HT3 receptor agonist, facilitated the aversive responses in the second phase whereas that of 8-OH-DPAT, a selective 5-HT1A receptor agonist, suppressed them. Intrathecal administration of 5-HT showed a dual effect on the second phase of the aversive responses in the 5,7-DHT-treated rats; 5-HT inhibited the aversive responses when administered at a low dose (0.1 nmol/rat) but facilitated them at a high dose (1 nmol/rat). In addition, the inhibitory and facilitatory effects of intrathecal 5-HT were blocked by its co-administration with NAN190, a 5-HT1A receptor antagonist, and granisetron, respectively. These results suggest that 5-HT suppresses formalin-induced nociception in the spinal cord via the 5-HT1A receptor and facilitates it via the 5-HT3 receptor.
Oyama
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Ueda
M
M
Kuraishi
Y
Y
Akaike
A
A
Satoh
M
M
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D017829:Granisetron / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D015116:5,7-Dihydroxytryptamine; D005557:Formaldehyde; D017829:Granisetron; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists