Differential expression of the AP-1/CRE-binding proteins FOS and CREB in preproenkephalin mRNA-expressing neurons of the rat parabrachial nucleus after nociceptive stimulation.

Several subgroups in the brainstem parabrachial nucleus (PB), which is a major target for nociresponsive neurons in the medullary and spinal dorsal horn, contain large numbers of preproenkephalin (ppENK) mRNA-expressing neurons. To elucidate how noxious stimuli may regulate ppENK transcription in these neurons, we have in the present study investigated whether immunoreactivity for the transcription factors FOS and phosphorylated CREB (pCREB), respectively, is displayed in the ppENK mRNA-expressing neurons after peripheral nociceptive stimulation. Rats received injection of formalin into one hindpaw, and were killed 30-80 min later. With a combination of immunohistochemistry and in situ hybridization, we found that only a small number of ppENK mRNA-expressing neurons in PB displayed FOS-immunoreactivity after nociceptive stimulation. In contrast, large numbers of ppENK mRNA-expressing neurons displayed pCREB-like immunoreactivity after nociceptive stimulation. Most of the ppENK mRNA/pCREB-expressing neurons were found in the Kölliker-Fuse and internal lateral subnuclei, but many double-labeled cells were also seen in the ventral lateral and central lateral subnuclei. In addition, a cluster of ppENK mRNA/pCREB-expressing neurons was found in the medial part of the medial parabrachial nucleus. Our findings suggest that CREB rather than FOS regulates nociceptive-related second messenger activation of ppENK transcription in parabrachial neurons.