Pain- and morphine-associated transcriptional regulation of neuropeptide FF and the G-protein-coupled NPFF2 receptor gene.

Neuropeptide FF (NPFF) is involved in pain modulation, especially plasticity during inflammatory and neuropathic pain, and opiate interactions. Its nociceptive functions may be mediated by the NPFF2 receptor. To elucidate the role of the NPFF system in plasticity associated with pathologic pain, we studied the changes of NPFF mRNA and NPFF2 receptor mRNA in rat models of acute colonic inflammation, inflammatory pain, and neuropathic pain. Furthermore, we studied the mRNA levels of both NPFF and NPFF2 receptor in morphine-tolerant rats and after acute morphine injections. We found an activation of spinal NPFF and NPFF2 receptor during early inflammatory pain. Supraspinally, we found an up-regulation of NPFF2 receptor mRNA during acute colonic inflammation and neuropathic pain. Acute, but not chronic, morphine activated the genes supraspinally. The results give further evidence for the involvement of the NPFF system in pain modulation and may provide new therapeutic opportunities for pathologic pain.