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

作者：Hama Aldric T^*; Plum Ann Woodhouse; Sagen Jacqueline

来源：Pharmacology Biochemistry and Behavior, 2010, 97(2): 249-255.

DOI：10.1016/j.pbb.2010.08.006

• Allodynia
• Hyperalgesia
• Local anesthetic
• Mucolytic
• Off-label use
• Voltage-gated Na(+) channel

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.

• 出版日期2010-12