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.