Title:Targeting of Peripherally Expressed Pain-Related Molecules in Injury- Induced Chronic Neuropathic Pain
Volume: 13
Issue: 5
Author(s): Takashi Hirai and Aldric Hama
Affiliation:
Keywords:
Animal models, gene-specific therapy, multi-target therapy, peripheral nervous system.
Abstract: Neuropathic pain is a chronic disability associated with a dysfunction of the nervous system, initiated by a
primary lesion or disease. Even after resolution of the initiating pathology, neuropathic pain often persists, leading to a
significantly diminished quality of life. A vast literature has documented alterations in the expression and distribution of
various pain-related proteins in the peripheral nervous system following injury or disease. The current review examines
pain-related molecules in the pathogenesis of peripheral nerve injury-induced pain and discusses potentially useful
therapeutic targets on the basis of preclinical findings in rodent neuropathic pain models. There are indeed a number of
cellular processes that are involved in maintaining the neuropathic pain state, but the current review will focus on
transmembrane proteins, particularly the voltage-gated and ligand-gated ion channels, which modulate peripheral nerve
function. Given the complexity of the process involved in peripheral nerves, clinical efficacy could be greatly enhanced if
several of these targets are engaged at once. A key advantage of therapy directed peripherally is that penetration of the
therapeutic into the CNS is not entirely necessary, thereby reducing the risk of adverse psychomotor effects. While a
number of fascinating targets have been identified in preclinical rodent models, there is a need to confirm that they are in
fact relevant to clinical neuropathic pain. Thus, the current review will also discuss the extent to which clinical data
confirms the findings of preclinical studies.