Anesthesia and analgesia
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Anesthesia and analgesia · Jan 2006
Comparative StudyThe antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors?
Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channels, N-methyl-d-aspartic acid (NMDA) receptors, and Ca2+ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. ⋯ The Ca2+ channel blocker of N-type (omega-conotoxin GVIA, 0.1-3 microg), but not of P/Q-type (omega-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and omega-conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca2+ channel activator. These results provide correlative evidence to support the contention that N-type Ca2+ channels, but not K(ATP) channels or NMDA or GABA(A) receptors, might be involved in the antiallodynic effect of intrathecal gabapentin.
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Anesthesia and analgesia · Jan 2006
Comparative StudyDoxepin by topical application and intrathecal route in rats.
The tricyclic antidepressant, doxepin, has been reported to be a potent local anesthetic in rat sciatic nerve blockade. We hypothesized that topical doxepin has significantly longer antinociception compared with control and intrathecally compared with bupivacaine. Solutions of 0.3 mL of doxepin at 50, 75, and 100 mM and control (only the vehicle solution) were applied as a patch to the shaved dorsal skin of rats. ⋯ Topical doxepin at concentrations of 75 mM and 100 mM was significantly more effective than control (P < 0.05). Complete recovery for the 100-mM concentration occurred at 60 h, although two of five rats demonstrated erythema and scarring. Intrathecally, 20 mM of doxepin was not significantly different for motor and proprioceptive function from 23 mM (0.75%) bupivacaine; however, neurotoxicity (defined as persistent neurological deficit) commenced at 50 mM.