Does COX2-dependent PGE2 play a role in neuropathic pain?

Neuropathic pain (NeP) is a common chronic pain state with unmet medical needs. Due to poorly defined underlying mechanisms, current therapies for NeP are far from satisfactory. Mounting evidence suggests that long-term plasticity in pain signaling pathways underpins the pathogenesis of NeP. Inflammatory responses in injured nerves have been recognized as important events initially sensitizing nociceptive neurons and subsequently inducing long-term plasticity in the dorsal root ganglion. Inflammatory cells such as invading macrophages and Schwann cells produce a wide array of inflammatory mediators. Cyclooxygenase 2-dependent prostaglandin E2 (COX2/PGE2) is one of the important mediator abundantly produced in injured nerves and involved in the genesis of NeP. In this mini-review, we highlight possible novel mechanisms underlying the role of COX2/PGE2 in injured nerves in the genesis of NeP. Long lasting COX2/PGE2 in injured nerves may induce chronic effects on nociceptors to facilitate the synthesis of pain-related molecules by stimulating 'en passant' injured or spared axons. COX2/PGE2 may also induce chronic effects on local inflammatory cells in injured nerves to facilitate the synthesis of inflammatory mediators via autocrine and paracrine pathways. COX2/PGE2 in injured nerves and downstream PGE2 EP receptor signaling should be considered as therapeutic targets to more effectively treat chronic NeP.