title: Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain.
abstract: 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.
authors: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ahama@med.miami.edu
authors: Aldric T
authors: AT
authors: Hama
authors: Ann Woodhouse
authors: AW
authors: Plum
authors: Jacqueline
authors: J
authors: Sagen
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D026941:Sodium Channel Blockers; D000551:Ambroxol