Involvement of ventrolateral orbital cortex 5-HT 1-7 receptors in 5-HT induced depression of spared nerve injury allodynia

The present study examined the roles of ventrolateral orbital cortex (VLO) 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptor subtypes in mediating 5-HT-induced antiallodynic actions in the rat spared nerve injury (SNI) pain model. Changes in paw withdrawal threshold (PWT) were measured using von-Frey filaments. Microinjection of 5-HT (2, 5 and 10 μg, in 0.5 μl) into the VLO depressed allodynia induced by SNI, and the PWT increased in a dose-dependent manner. Microinjection of selective 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT5A, 5-HT6 and 5-HT7 receptor antagonists, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190) (10 μg), cyproheptadine (50 ng), granisetron hydrochloride (granisetron) (10 μg), 1-[2-[(methylsulfonyl)-amino]ethyl]-4-piperidinyl]methyl1-methyl-1H-indole-3-carboxylate (GR113808) (5 μg), SB699551 dihydrochloride (SB699551) (10 μg), SB258585 dihydrochloride (SB258585) (2 μg) or SB269970 hydrochloride (SB269970) (10 μg) into the VLO 5-min prior to 5-HT (10 μg) injection, all antagonized the 5-HT-induced inhibition of allodynia. In addition, these antagonists applied alone to VLO did not influence allodynia. These results suggest that although 5-HT1-7 receptor subtypes in the VLO do not have a tonic modulatory action on the allodynia induced by SNI, they are involved in mediating the depression of the SNI allodynia produced by injection of 5HT into VLO.

95Highlights► 5-HT applied to VLO reduced mechanical allodynia induced by SNI in rats. ► 5-HT 1-7 receptor antagonist reduced 5-HT-induced inhibition of allodynia. ► 5-HT 1-7 receptor subtypes mediated antiallodynia of 5-HT in VLO.