Ranolazine attenuates behavioral signs of neuropathic pain

Abstract

Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.

Conflict of interest statement

Conflicts: HJG is a research consultant for Gilead Sciences. ID is Vice President for Neuroscience for Gilead Sciences.

Figures

Figure 1

I.p. administration of ranolazine dose-dependently increases paw withdrawal threshold to a mechanical stimulus (A) and reduces response duration to a cool stimulus (B). Values represent mean ± SEM. Number of animals per group are in parentheses. +p<0.05 saline vs 100; *p<0.05 saline vs 100 and 30; (star) p<0.05 saline vs 100 and 30 and 10.

Figure 2

Oral administration of ranolazine dose-dependently increases paw withdrawal threshold to a mechanical stimulus (A) and reduces response duration to a cool stimulus (B). Values represent mean ± SEM. Number of animals per group are in parentheses. +p<0.05 saline vs 100; *p<0.05 saline vs 100 and 30; (star) p<0.05 saline vs 100 and 30 and 10.