Targeting invading macrophage-derived PGE2, IL-6 and calcitonin gene-related peptide in injured nerve to treat neuropathic pain.

Immune and inflammatory responses occurring in an injured nerve have been generally believed to contribute to the generation and maintenance of neuropathic pain. In this review, the authors demonstrate the upregulation of COX-2/prostaglandin E2, IL-6 and calcitonin gene-related peptide in invading macrophages and discuss possible mechanisms involved in their upregulation and how they contribute to the maintenance of neuropathic pain. By acting on nociceptors in dorsal root ganglion and local inflammatory cells via autocrine or paracrine pathways, these inflammatory mediators facilitate spontaneous ectopic activity and sustain nociceptive responses, an important mechanism underlying both ongoing and evoked neuropathic pain state. Targeting these mediators in injured nerve may provide novel therapeutic avenues to more successfully treat nerve injury-associated neuropathic pain.