Hyperalgesic effects of divalent cations and antinociceptive effects of a calcium chelator in naive and morphine-dependent mice.
Using a modified tail-flick procedure we have found a highly significant hyperalgesic response in narcotic dependent mice peaking 12 hr following the removal of chronically implanted morphine pellets. Withdrawal-induced hyperalgesia correlated well with other signs of opiate withdrawal behavior. Intracerebroventricular injections of CaCl2, MnCl2 further enhanced the hyperalgesic response in morphine-dependent mice; morphine-dependent mice were more than twice as sensitive to calcium-induced hyperalgesia as placebo-treated controls. On the other hand, i.c.v. injections of the calcium-specific chelator EGTA produced highly significant, dose-dependent antinociceptive responses in both morphine-dependent and control mice, but morphine dependent mice were only half as sensitive to EGTA-induced analgesia as controls. Withdrawal hyperalgesia and EGTA analgesia may be directly related to changes in brain localization of calcium that have been reported previously; it is concluded that morphine and EGTA-induced analgesia may be associated with a calcium depleted state within a relatively small calcium pool of the nerve cell and that opiate withdrawal hyperalgesia is a sensitive measure of narcotic dependency that is likely associated with an increased Ca++ content in the same region.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002412:Cations; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005026:Ethylene Glycols / Q000494:pharmacology*; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000188:drug therapy / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology*
D002412:Cations; D005026:Ethylene Glycols; D004533:Egtazic Acid; D002118:Calcium