Role of peripheral 5-HT(4), 5-HT(6), and 5-HT(7) receptors in development and maintenance of secondary mechanical allodynia and hyperalgesia.
The role of 5-hydroxytryptamine (5-HT)(4), 5-HT(6), and 5-HT(7) receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia. Pretreatment (-10min) with cromoglycate (195-1950nmol/paw) partially inhibited acute nociceptive behaviors and completely prevented secondary allodynia and hyperalgesia on day 6 after injection. Ipsilateral peripheral pretreatment with the selective 5-HT(4) (ML-10302, 1-100nmol/paw), 5-HT(6) (EMD-386088, 0.001-0.01nmol/paw), and 5-HT(7) (LP-12, 0.01-100nmol/paw) receptor agonists significantly increased secondary allodynia and hyperalgesia in both paws. In contrast, ipsilateral peripheral pretreatment with the selective 5-HT(4) (GR-125487, 1-100nmol/paw), 5-HT(6) (SB-258585, 0.00001-0.001nmol/paw), and 5-HT(7) (SB-269970, 0.1-10nmol/paw) receptor antagonists significantly prevented formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of ML-10302 (100nmol/paw), EMD-386088 (0.01nmol/paw), and LP-12 (100nmol/paw) were completely prevented by GR-125487 (5-HT(4) antagonist, 1nmol/paw), SB-258585 (5-HT(6) antagonist, 0.00001nmol/paw), and SB-269970 (5-HT(7), antagonist, 0.01nmol/paw), respectively. Ipsilateral peripheral posttreatment with cromoglycate or GR-125487 (1-100nmol/paw), SB-258585 (0.001-0.1nmol/paw), and SB-269970 (0.1-10nmol/paw) reversed formalin-induced secondary allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT(4), 5-HT(6), and 5-HT(7) receptors participate in the development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. 5-hydroxytryptamine (5-HT) released in peripheral tissues after formalin injection sensitized primary afferent neurons via 5-HT(4), 5-HT(6), and 5-HT(7) receptors, leading to development and maintenance of secondary allodynia and hyperalgesia.
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México DF, Mexico.
Beatriz
B
Godínez-Chaparro
Paulino
P
Barragán-Iglesias
Gabriela
G
Castañeda-Corral
Héctor I
HI
Rocha-González
Vinicio
V
Granados-Soto
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D019540:Area Under Curve; D004205:Cromolyn Sodium / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D013997:Time Factors; D000094942:Nociceptin Receptor
D018927:Anti-Asthmatic Agents; D004205:Cromolyn Sodium; D005557:Formaldehyde; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; D018490:Serotonin Agents; D000094942:Nociceptin Receptor; C097216:serotonin 6 receptor; C104425:serotonin 7 receptor; C000722285:Oprl1 protein, rat
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