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.
Original language | English (US) |
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Pages (from-to) | 249-255 |
Number of pages | 7 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 97 |
Issue number | 2 |
DOIs | |
State | Published - Dec 2010 |
Keywords
- Allodynia
- Hyperalgesia
- Local anesthetic
- Mucolytic
- Off-label use
- Voltage-gated Na channel
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Pharmacology
- Toxicology
- Behavioral Neuroscience
- Biological Psychiatry