BJA Advance Access published online on May 28, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aen107
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Neuropathic pain: emerging treatments
AstraZeneca Research and Development, 7171 Frederick Banting Street, Montreal, Canada H4S 1Z9
* E-mail: andy.dray{at}astrazeneca.com
Neuropathic pain remains one of the most challenging of all neurological diseases and presents a large unmet need for improved therapies. Many mechanistic details are still lacking, but greater knowledge of overlapping mechanisms and disease comorbidities has highlighted key areas for intervention. These include peripheral and central hyperexcitability. Among the molecular drivers are ion channels (Nav1.7, Nav1.8, Nav1.3, Cav2.2, and alpha2-delta subunits) whose expression is changed during neuropathic pain and their block shows therapeutic utility. Block of a number of ligand-gated channels [transient receptor potential (TRP)V1, TRPM8, and neuronal nicotinic receptors (NNRs)], important in neural sensitization, may also prove beneficial. Other approaches, such as the modulation of peripheral excitability via CB1 receptors, reduction of spinal excitability through block of glutamate receptors (metabotropic glutamate receptor 5 and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate), block of activated spinal neuroglial (CCR2 and P2X7), or increasing spinal inhibition by enhancing monoaminergic activity, all offer exciting opportunities currently being validated in the clinic. Finally of note is the emergence of biological approaches, for example, antibodies, siRNA, gene therapy, offering powerful therapeutic additions with which to redress the neurological disease imbalances causing neuropathic pain.
Keywords: glia; ions, ion channels; neuroinflammation; pain, chronic; pathophysiology; receptors, cannabinoid; receptors, glutamate; receptors, TRP
Declaration of interest. A.D. works in Research and Development at AstraZeneca.
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