Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats.
In patients and animals with painful peripheral neuropathies, spontaneous ectopic discharge from injured primary afferents is hypothesized to maintain a central state of hyperexcitability that underlies hyperalgesia and allodynia. Temporary suppression of this discharge allows the central state to normalize, such that hyperalgesia and allodynia are absent or reduced until the resumption of the discharge rekindles central hyperexcitability. Previous work suggests that Ca++ channels are involved in the genesis of spontaneous discharge from injured afferents. We applied SNX-111 and SNX-124 (0.1-3.0 micrograms), synthetic homologs of omega-conopeptides (MVIIA and GVIA, respectively) and potent blockers of neuronal N-type voltage-sensitive Ca++ channels, to the site of nerve injury via chronically implanted perineural cannulae in rats with an experimental painful peripheral neuropathy (the chronic constriction injury model). Heat-hyperalgesia and mechano-allodynia were reduced for at least 3 hr. Drug application to a normal nerve had no effect on responses to heat or mechanical stimuli. These results suggest that N-type Ca++ channel blockers may be useful in the treatment of the abnormal pains that occur after nerve injury.
Xiao
W H
WH
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA.
Bennett
G J
GJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D020960:omega-Conotoxins; C078452:ziconotide; D020866:omega-Conotoxin GVIA