Evaluation of the anti-hyperalgesic and anti-allodynic effects of cathepsin S inhibition in a murine model of neuropathic pain

摘要

Cathepsin S has been identified as a potential target for therapeutic intervention in the treatment of neuropathic pain. Preclinical testing of cathepsin S inhibitors in rat models of neuropathic pain is complicated due to sequence heterogeneity both within and between different rat strains. To circumvent this issue we sought to validate a murine model of neuropathic pain. This study examined the effects of LHVS a known irreversible inhibitor of both mouse and human cathepsin S protease activity in a murine photochemically-induced partial sciatic nerve injury model. LHVS had anti-allodynic and anti-nociceptive effects on all the tests involving the partially denervated hindpaw, including mechanical, cold and radiant heat stimuli and on the tail flick test. These effects were comparable to that of morphine. This neuropathic pain model represents a suitable preclinical model for evaluating the anti-allodynic and anti-hyperalgesic effects of cathepsin S inhibitors during the drug development process.