Pharmacologic reversal of pertussis toxin-induced thermal allodynia in mice.
We have previously demonstrated that the intrathecal administration of pertussis toxin produces a long-lasting thermal allodynia in mice. The purpose of the present studies was to compare the antinociceptive and the antiallodynic effects of drugs that are commonly used in treating neuropathic allodynia in untreated mice and in mice which had been administered vehicle or pertussis toxin intrathecally 7 days previously. In untreated mice, morphine, fentanyl, clonidine, oxymetazoline, desipramine and lidocaine, but not MK801, produced dose-related antinociception when tested using a 55 degrees C water tail-flick test. However, 7 days after the intrathecal injection of pertussis toxin, which induced a condition of thermal allodynia when tested using a 45 degrees C water bath, the full opioid and the full alpha(2)-adrenergic receptor agonists fentanyl and clonidine, but not the partial opioid nor the partial alpha(2)-adrenergic receptor agonists morphine and oxymetazoline, reversed the pertussis toxin-induced thermal allodynia. Moreover, lidocaine, desipramine, carbamazepine and MK801 failed to reverse the pertussis toxin-induced thermal allodynia. The present results suggest that decrements in G(i)/G(o)-protein function may be involved in initiating and/or maintaining some neuropathic pain states. Moreover, the results of the present study suggest that the use of full, but not partial, opioid or alpha(2)-agonists may be useful in the treatment of thermal allodynic pain states which may be due at least in part to inhibitory second messenger system dysfunction. Further, the underlying biochemistry of the apparent allodynic pain state induced by intrathecal administration of pertussis toxin warrants further investigation.
Womer
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DE
Lilly Research Laboratories, Lilly Corporate Center, 46285-0510, Indianapolis, IN, USA.
Shannon
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HE
D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement; D037342:Pertussis Toxin; D013696:Temperature; D010566:Virulence Factors, Bordetella / Q000009:adverse effects*
D010566:Virulence Factors, Bordetella; D002220:Carbamazepine; D016291:Dizocilpine Maleate; D009020:Morphine; D010109:Oxymetazoline; D008012:Lidocaine; D037342:Pertussis Toxin; D003000:Clonidine; D003891:Desipramine; D005283:Fentanyl