Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia.
Peripheral nerve lesions can result in exaggerated pain responses to low intensity mechanical stimuli (tactile allodynia). In the present work, the pharmacology of voltage-dependent calcium channels (VDCCs) involved in the transmission of neuropathic pain was characterized by examining the effects of antagonists specific to the N-, L- and P-type VDCCs, as well as an antagonist at a non-L-, non-N-type site. Drugs were administered via chronic lumbar intrathecal, i.v. or regional nerve block catheters implanted in rats with tactile allodynia induced by tight ligation of the left fifth and sixth lumbar spinal nerves. Intrathecally delivered N-type VDCC (omega-conopeptides SNX239, SNX159 and SNX111) produced dose-dependent blockade of tactile allodynia. Intrathecal L-type (diltiazem, verapamil and nimodipine), non-N-, non-L-type (omega-conopeptide SNX230) and P-type (omega-agatoxin IVA) VDCC antagonists had no effect on pain behavior at the highest doses examined. No VDCC antagonist suppressed paw withdrawal when administered i.v. SNX239, although effective when administered intrathecally, was without effect when applied regionally to the injured portion of the nerve. These results emphasize the importance of N-type, but not L- or P- type, VDCCs in the spinal cord on systems mediating persistent tactile allodynia after nerve injury.
Anesthesiology Research Laboratory, University of California, San Diego.
S R
SR
Chaplan
J W
JW
Pogrel
T L
TL
Yaksh
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000209:etiology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects; D013127:Spinal Nerves / Q000293:injuries*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C078452:ziconotide