Evidence for a spinal serotonergic control of the peripheral inflammation in the rat.
We investigated the effect of serotonergic agonists and antagonists injected intrathecally by direct punction of the spinal cord at the lumbar level (between L5-L6) on peripheral inflammatory edema. Edema was induced by carrageenan injected subcutaneously in one hindpaw 30 min after spinal treatments. Serotonin (0.1, 1, 10 pmol) caused a graded-inhibition of the inflammatory paw edema. The corticosteroid inhibitor aminoglutethimide (100 mg/kg, p.o. 1.5 h before spinal treatment) did not modify this effect. The 5-HT1A agonist buspirone and the 5-HT1B/1D agonist sumatriptan (0.1, 1.0 and 10 nmol) also inhibited paw edema. The 5-HT1,2 antagonist methysergide (10 and 100 pmol) enhanced edema, but higher doses ( 4 and 8 nmol) diminished edema. NAN-190 (5-HT1 antagonist; 1 and 10 nmol) increased paw edema, while ritanserin (5-HT2 antagonist; 1 nmol) inhibited paw edema. Ondansetron (5-HT3 antagonist; up to 10 nmol) did not affect edema, but metoclopramide (5-HT3 antagonist / 5-HT4 agonist; 5, 10 and 30 pmol) inhibited edema. These data suggest that a tonic release of serotonin in the spinal cord may occurs during ongoing peripheral inflammation, modulating the neurogenic component of edema either by an inhibitory action on 5-HT1 receptors or by a stimulatory action on 5-HT2 receptors. A disfunction in such mechanism may be involved in the pathophysiology of certain types of headaches or migraine, which seem to depend on neurogenic vasodilation, and may also help to explain the therapeuthic effectiveness of some serotonergic agents in these conditions.
Daher
Josélia B
JB
Department of Pharmacology, CCB, Federal University of Santa, Catarina, Florianópolis, SC, 88040-900, Brazil.
de Melo
Marielle D
MD
Tonussi
Carlos R
CR
D000818:Animals; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006614:Hindlimb / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D013116:Spinal Cord / Q000503:physiopathology*
D016166:Free Radical Scavengers; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin