alexa Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain.
Neurology

Neurology

Journal of Neuroinfectious Diseases

Author(s): Gaida W, Klinder K, Arndt K, Weiser T

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Abstract Neuropathic pain affects many patients, and treatment today is far from being perfect. Nav1.8 Na(+) channels, which are expressed by small fibre sensory neurons, are promising targets for novel analgesics. Na(+) channel blockers used today, however, show only limited selectivity for this channel subtype, and can cause dose-limiting side effects. Recently, the secretolytic ambroxol was found to preferentially inhibit Nav1.8 channels. We used this compound as a tool to investigate whether a Nav1.8-preferring blocker can suppress symptoms of chronic, neuropathic and inflammatory pain in animal models. The drug was tested in the formalin paw model, two models of mononeuropathy, and a model of monoarthritis in rats. Ambroxol's effects were compared with those of gabapentin. Ambroxol at a dose of 1g/kg had to be administered to rats to achieve the plasma levels that are reached in clinical use (for the treatment of infant and acute respiratory distress syndrome). Ambroxol (1g/kg) was only weakly effective in models for acute pain, but effectively reduced pain symptoms in all other models; in some cases it completely reversed pain behaviour. In most cases the effects were more pronounced than those of gabapentin (at 100mg/kg). These data show that a Nav1.8-preferring Na(+) channel blocker can effectively suppress pain symptoms in a variety of models for chronic, neuropathic and inflammatory pain at plasma levels, which can be achieved in the clinic. This article was published in Neuropharmacology and referenced in Journal of Neuroinfectious Diseases

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