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

Neuropharmacology. 2005 Dec;49(8):1220-7. doi: 10.1016/j.neuropharm.2005.08.004. Epub 2005 Sep 21.


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.

MeSH terms

  • Ambroxol / pharmacology*
  • Amines / pharmacology
  • Analgesics*
  • Animals
  • Behavior, Animal / drug effects
  • Constriction, Pathologic / prevention & control
  • Constriction, Pathologic / psychology
  • Cyclohexanecarboxylic Acids / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Formaldehyde
  • Gabapentin
  • Inflammation / complications*
  • Inflammation / psychology
  • Ligation
  • Male
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / drug effects*
  • Pain / drug therapy*
  • Pain / etiology*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Wistar
  • Sciatic Neuropathy / complications*
  • Sciatic Neuropathy / psychology
  • Sodium Channel Blockers / pharmacology*
  • Sodium Channels / drug effects*
  • gamma-Aminobutyric Acid / pharmacology


  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Scn10a protein, rat
  • Sodium Channel Blockers
  • Sodium Channels
  • Formaldehyde
  • Ambroxol
  • gamma-Aminobutyric Acid
  • Gabapentin