Role of 5-HT1B/1D receptors in the reduction of formalin-induced nociception and secondary allodynia/hyperalgesia produced by antimigraine drugs in rats.

AIMS: The present study analyzed the potential antinociceptive effect of the antimigraine drugs sumatriptan, dihydroergotamine or methysergide in rats submitted to the formalin test. Moreover, by using selective antagonists, the role of 5-HT1B/1D serotonergic receptors was investigated in the antinociception induced by these antimigraine drugs. MAIN METHODS: The formalin test was used to assess the nociceptive activity. Overt pain-like behavior (flinching, 1h) and evoked nociception (long-lasting secondary mechanical allodynia and hyperalgesia, 6 days) were determined in the same rat. KEY FINDINGS: Ipsilateral, but not contralateral, pre-treatment (in µg/paw) with sumatriptan (10-300), methysergide (1-30) or dihydroergotamine (1-30) significantly prevented flinching behavior (at 1h) as well as secondary allodynia and hyperalgesia (at day 6) induced by formalin. Interestingly, the antinociceptive (flinching), antiallodynic and antihyperalgesic effects of sumatriptan were completely prevented by peripheral pre-treatment with selective antagonists at the 5-HT1B (SB 224289; 100) or 5-HT1D (BRL 15572; 100) receptors. In contrast, the acute antinociceptive effects of methysergide and dihydroergotamine were partially prevented by SB 224289 and BRL 15572. The antiallodynic and antihyperalgesic effects of both drugs were completely prevented by BRL 15572 and partially prevented by SB 224289. Given alone, SB 224289 or BRL 15572 did not modify per se the long-lasting secondary allodynia and hyperalgesia. SIGNIFICANCE: The above findings suggest that: (i) the antimigraine drugs sumatriptan, methysergide and dihydroergotamine reduce the acute and chronic nociception induced by formalin; and (ii) this antinociceptive effect results from activation of peripheral 5-HT1B/1D serotonergic receptors.

Acid increases inflammatory pain in rats: effect of local peripheral ASICs inhibitors.

The purpose of this study was to assess the possible antinociceptive effect of the acid sensing ion channels (ASICs) inhibitors amiloride and benzamil after local peripheral administration in three models of inflammatory pain in rats. Reduction of pH, from 7.4 to 5.8 units, significantly increased the flinching/licking behavior induced by either 0.1% serotonin, 0.1% capsaicin or 0.5% formalin. Local peripheral ipsilateral, but not contralateral, injection of amiloride or benzamil significantly reduced nociceptive behaviors (flinching and licking/lifting) induced by serotonin, capsaicin or formalin in acidic conditions (pH 6.2). Interestingly, benzamil produced antinociception at low doses (0.001-0.1 microM/paw) while higher doses (1 microM/paw) did not affect capsaicin- or formalin-induced licking/lifting. Our data suggest that local peripheral inhibition of ASICs play an important role in inflammatory pain.