Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggest that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain.

Research Highlights
► The mucolytic and local anesthetic drug ambroxol was tested in a rat model of neuropathic spinal cord injury pain.
► Systemic administration of ambroxol significantly attenuated below-lesion cutaneous hypersensitivity.
► A possible mechanism of the antinociceptive effect is via block of voltage-gated sodium channels found on peripheral nociceptors since ambroxol, at the tested doses, does not pass the blood–brain barrier.
► Ambroxol could be a clinically useful analgesic drug for a variety of neuropathic pain states.