Neural mechanism underlying hyperalgesic response to orofacial pain in Parkinson's disease model rats

Abstract

To investigate the neural mechanism of pain originating from the orofacial region in PD patients, we used PD model rats produced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. We investigated effects of nigrostriatal lesions on the behavioral response (face rubbing) to formalin injection into the upper lip. We also examined expression of c-Fos and phosphorylated extracellular signal-regulated kinase (pERK) in the trigeminal spinal subnucleus caudalis (Vc) and expression of c-Fos in the periaqueductal gray matter (PAG). Face rubbings following formalin injection showed a biphasic profile, with the first phase for the first 5 min and the second phase from 10 to 90 min. Rats with 6-OHDA lesions showed increased face rubbings in the second phase when formalin was injected ipsilaterally to the lesion, and c-Fos expression in the Vc increased. When formalin was injected contralaterally, face rubbings were reduced in the first phase, however, expression levels of c-Fos and pERK in the Vc were unchanged. No significant difference was found in c-Fos expression in the PAG between 6-OHDA- and saline-injected rats. These results suggest that unilateral dopamine depletion in the nigrostriatal pathway may be involved in hypersensitivity to noxious stimulation delivered to the orofacial region.

Keywords: 6-Hydroxydopamine; Formalin; Medial forebrain bundle; Parkinson's disease; Periaqueductal gray matter; Trigeminal spinal subnucleus caudalis; Tyrosine hydroxylase; c-Fos.