Pretreatment with antiserum against dynorphin, substance P, or cholecystokinin enhances the morphine-produced anti-allodynia in the sciatic nerve ligated mice.
It is generally accepted that neuropathic pain is resistant to amelioration by morphine in clinical studies and insensitivity to intrathecal (i.t.) administered morphine in experimental models of neuropathic pain has been demonstrated. This study is to determine if endogenous dynorphin, substance P or cholecystokinin is involved in the lack of anti-allodynia of morphine in a partial sciatic nerve ligation (PSL) model of CD-1 mice. Mice exhibited tactile allodynia in the ipsilateral hind paw 1 day after PSL, and reached its maximal allodynic effect at 2 days and remained allodynic for 7 days. Morphine (3.0 nmol) given i.t. did not alter the tactile allodynic threshold in ipsilateral paw of mice pretreated i.t. with normal rabbit serum 2 days after PSL. However, the same dose of morphine (3.0 nmol) given i.t. reduced markedly allodynia in mice pretreated for 2h with antiserum against dynorphin A(1-17) (200 microg); the morphine-produced anti-allodynia developed slowly, reached its peak effect at 30 min and returned to an allodynic state in 60 min. Similarly, i.t. injection of morphine reduced the allodynia in PSL mice pretreated with antiserum against substance P (10 microg) or cholecystokinin (200 microg) for 2h. Intrathecal pretreatment with antiserum against dynorphin A(1-17), substance P or cholecystokinin for 2h injected alone did not affect the baseline mechanical tactile threshold in ipsilateral paw 2 days after PSL. The results indicate that endogenous dynorphin A(1-17), substance P and cholecystokinin are involved in PSL-induced neuropathic allodynia to attenuate the anti-allodynic effect of morphine.
Department of Anesthesiology, Medical College of Wisconsin, Medical Education Building, Room M4308, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Hsiang-En
HE
Wu
Emma T
ET
Schwasinger
Jau-Shyong
JS
Hong
Leon F
LF
Tseng
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000819:agonists; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D004399:Dynorphins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology*; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000819:agonists*; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000701:Analgesics, Opioid; D000906:Antibodies; D007106:Immune Sera; D013373:Substance P; D004399:Dynorphins; D009020:Morphine; D002766:Cholecystokinin