Role of ventrolateral orbital cortex 5-HTreceptors in formalin-induced secondary mechanical allodynia and hyperalgesia.

Abstract

BACKGROUND: Formalin injection in hindpaw of rat produced acute nociceptive behaviors (flinching and licking/lifting) followed by secondary mechanical allodynia and hyperalgesia. Our previous study suggests that 5-HTreceptors in the ventrolateral orbital cortex (VLO) are involved in Formalin produced acute nociceptive behaviors, but it is not clear whether 5-HTreceptors are involved in secondary mechanical allodynia and hyperalgesia. The purpose of this present study is to unveil the role of 5-HTreceptors in the VLO and the underlying mechanisms in formalin-induced secondary mechanical allodynia and hyperalgesia. RESULTS: The expression level of 5-HTreceptors were significantly increased in the VLO tissues at 6 days after formalin injection. Microinjection of the 5-HTreceptors agonist DOI into the VLO decreases formalin-induced secondary mechanical allodynia and hyperalgesia in the ipsilateral paw, but not contralateral paw, which was antagonized by pre-treatment with 5-HTreceptors antagonist Ketanserin. Furthermore, the antinociceptive effect of DOI was blocked by the phospholipase C (PLC) inhibitor U73122 and the protein kinase C (PKC) inhibitor Chelerythrine, or the non-selective glutamate receptor antagonist Kynurenic acid. respectively. And the antinociceptive effect of DOI was blocked by pre-treatment with GABA in the ventrolateral periaqueductal grey (PAG). CONCLUSIONS: These data suggest that 5-HTreceptors in the VLO are involved in mediating the antinociceptive effect of formalin-induced long-lasting hypersensitivity. The possible mechanism underlying this effect is that 5-HTreceptors activation regulate glutamatergic neuron transmission via the Gq-PLC-PKC pathway, leading to activation of VLO neurons projecting to the PAG. This could activate the PAG brainstem descending inhibitory system and depression of nociceptive information transmission at the spinal cord level.