Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression: a hybridization study using two different rat models for nociception.

The density and distribution of N-methyl-D-aspartate receptor (NMDAR1) mRNA expression in the rat midbrain Periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation or chronic constrictive injury (CCI) as models for chronic peripheral nociception were examined using the in situ hybridization technique. The NMDAR1 hybridization signal intensities increased significantly in the ventrolateral areas of the caudal and middle thirds of the PAG after 3 days of Complete Freund's Adjuvant (CFA) injection. Likewise, rats subjected to CCI showed significant increases in hybridization signal intensities in comparison to sham operated animals in both the ipsi and contra-lateral ventrolateral quadrants of the caudal and middle thirds of the PAG. In the caudal dorsal raphe, the CFA and the CCI treated animals showed a significant increase in signal hybridization compared to control and sham operated groups while the rostral dorsal raphe showed no significant changes in either CCI or CFA treated groups. In contrast, there was no significant change in signal intensity of NMDAR1 mRNA in the dorsal subdivisions of the PAG following either CCI or CFA treatment. These results demonstrate significant bilateral increase in NMDAR1 mRNA expression in the ventrolateral areas of the caudal and middle thirds of the PAG and the caudal half of the dorsal raphe following chronic nociception. The up-regulation phenomenon may constitute a reactive mechanism against chronic neuropathic pain in the PAG.