The role of peripheral 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F serotonergic receptors in the reduction of nociception in rats.
This study assessed the possible antinociceptive role of peripheral 5-HT(1) receptor subtypes in the rat formalin test. Rats were injected into the dorsum of the hind paw with 50 microl of diluted formalin (1%). Nociceptive behavior was quantified as the number of flinches of the injected paw. Reduction of flinching was considered as antinociception. Ipsilateral, but not contralateral, peripheral administration of the 5-HT(1) receptor agonists R(+)-UH-301 (5-HT(1A); 0.1-3 microg/paw), CGS-12066A (5-HT(1B); 0.01-0.3 microg/paw), GR46611 (5-HT(1B/1D); 0.3-10 microg/paw), BRL54443 (5-HT(1E/1F); 3-300 microg/paw) or LY344864 (5-HT(1F); 3-300 microg/paw) significantly reduced formalin-induced flinching. The corresponding vehicle was devoid of any effect by itself. The local antinociceptive effect of R(+)-UH-301 (0.3 microg/paw) was significantly reduced by WAY-100635 (30-100 microg/paw; a 5-HT(1A) receptor antagonist). Moreover, the antagonists GR55562 (30-100 microg/paw; 5-HT(1B/D)) or SB224289 (30-100 microg/paw; 5-HT(1B)) dose-dependently reduced the antinociceptive effect of CGS-12066A (0.3 microg/paw) whereas GR55562 (30-100 microg/paw) or BRL15572 (30-100 microg/paw, 5-HT(1D)) reduced the antinociceptive effect of GR46611 (0.3 microg/paw). Interestingly, the effects of BRL54443 and LY344864 (300 microg/paw each) were partially reduced by methiothepin, but not by the highest doses of WAY-100635, SB224289 or BRL15572. The above antagonists did not produce any effect by themselves. These results suggest that peripheral activation of the 5-HT(1A,) 5-HT(1B), 5-HT(1D), 5-HT(1F) and, probably, 5-HT(1E) receptor subtypes leads to antinociception in the rat formalin test. Thus, the use of selective 5-HT(1) receptor agonists could be a therapeutic strategy to reduce inflammatory pain.
Granados-Soto
V
V
Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada Tenorios 235, México, DF, Mexico. vgranados@prodigy.net.mx
Argüelles
C F
CF
Rocha-González
H I
HI
Godínez-Chaparro
B
B
Flores-Murrieta
F J
FJ
Villalón
C M
CM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde; D007839:Functional Laterality; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000096642:Receptor, Serotonin, 5-HT1F
D005557:Formaldehyde; D044282:Receptor, Serotonin, 5-HT1A; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F; C076396:serotonin 1E receptor