Temporal changes of preproenkephalin mRNA and leu-enkephalin-like immunoreactivity in the neurons of the caudal spinal trigeminal nucleus and upper cervical cord after noxious stimuli.

The changing levels of preproenkephalin (PPE) mRNA expression and leu-enkephalin-like immunoreactivity (L-ENK-LI) in the caudal spinal trigeminal nucleus (Vc) and the upper cervical cord subsequent to subcutaneous injection of formalin into orofacial region were examined using in situ hybridization histochemistry and immunohistochemistry. Formalin injection resulted in a significant increase in the number of neurons expressing PPE mRNA in the superficial (laminae I-II) and deep (lamina V) layers of the ipsilateral Vc and the first cervical cord (C1). The expression of PPE mRNA increased 2 h and 4 h after formalin injection in the neurons of deep layer and superficial layers of the Vc, respectively. An increased expression of PPE gene could still be observed 48 h after formalin injection. The PPE mRNA expression in the neurons of the C1 had similar temporal changes as in the Vc. In parallel, the L-ENK-LI did not show any significant changes in the Vc and C1. These results indicate that peripheral noxious stimulation trans-synapticaly activates the expression of PPE gene in the neurons of the Vc and C1 and suggest that enkephallin (ENK) plays an important role in the processing and modulation of the oroficial noxious stimulation.