Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2013151 | Pharmacology Biochemistry and Behavior | 2010 | 7 Pages |
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.