Nigrostriatal dopaminergic depletion produces orofacial static mechanical allodynia.

Abstract

Dopamine is implicated in different orofacial pain-related diseases. The mechanisms underlying this invalidating pain are not yet understood. Therefore, the present study investigated if unilateral or bilateral lesions of the medial forebrain bundle (MFB) could induce a trigeminal static mechanical allodynia (SMA) comparable to that obtained after chronic construction injury of the infraorbital nerve (CCI-IoN) in rats. Unilateral and bilateral nigrostriatal lesions were obtained by injecting 6-hydroxydopamine into the MFB, and peripheral lesion was obtained by CCI-IoN. Static allodynia behaviour was tested by a mild non-noxious static von Frey filament stimulus. The analgesic effects of bromocriptine (D2R agonist) were assessed by both intraperitoneal and intracisternal injections. Finally, immunohistochemical study was done to investigate the implication of the protein kinase c isoform gamma (PKCγ) and the phosphorylated form of extracellular signal-related kinase 1/2 (pERK1/2) in pain sensitization at segmental level. 6-OHDA-lesioned animals developed SMA in the orofacial region as assessed by non-noxious stimuli. Intraperitoneal and intracisternal injections of bromocriptine alleviated this allodynic behaviour. Investigations within the medullary dorsal horn revealed an increase in PKCγ expression, a protein implicated in the chronicity of pain, within superficial laminae in 6-OHDA-lesioned rats. Also static mechanical stimulations of the orofacial region evoked increased expression of the molecular pain marker pERK1/2 in 6-OHDA-lesioned rats. Our data show that unilateral and bilateral dopamine depletion promoted trigeminal SMA comparable to that obtained after CCI-IoN. This allodynia can be alleviated by D2R activation, making D2R agonist a potential analgesic for orofacial neuropathic pain.