Therapeutic targets for the management of peripheral nerve injury-induced neuropathic pain.

Neuropathic pain is a debilitating form of treatment resistant chronic pain and responds poorly to the clinically available therapies. Studies from animal models of neuropathic pain have led to understanding of its pathobiology which includes complex interrelated pathways leading to peripheral and central neuronal sensitization. Advancements in the elucidation of neuropathic pain mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses these therapeutic targets including noradrenaline and 5-HT reuptake inhibitors; sodium, calcium and potassium channels; inhibitory and excitatory neurotransmitters; neuropeptides including bradykinin, tachykinin, cholecystokinin, neuropeptide Y, vasoactive intestinal peptide, and CGRP; pro-inflammatory cytokines; MAP kinases; PPAR γ; Na(+)/Ca(2+) exchanger; nitric oxide; purinergic receptors; neuronal nicotinic receptors; cation-dependent chloride transporters; oxidative stress; matrix metalloproteinase and plasminogen activators; growth factors; transient receptor potential (TRP) channels; endocannabinoids; histamine receptors; dopamine; sigma receptors, beta adrenergic receptors, endothelins, and D-amino acid oxidase. The exploitation of these targets may provide effective therapeutic agents for the management of peripheral nerve injury-induced neuropathic pain.