Hyperalgesia due to nerve injury: role of prostaglandins.
The hypothesis that prostaglandins contribute to hyperalgesia resulting from nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. Subcutaneous injection of indomethacin (a classic inhibitor of cyclo-oxygenase) into the affected hindpaw relieved mechanical hyperalgesia for up to 10 days after injection. Subcutaneous injection of meloxicam or SC-58125 (selective inhibitors of cyclo-oxygenase-2) into the affected hindpaw also relieved mechanical hyperalgesia, but with a shorter time-course. Subcutaneous injection of SC-19220 (an EP1 prostaglandin receptor blocker) into the affected hindpaw produced significant relief of mechanical and thermal hyperalgesia. Comparable injections into the contralateral paw or abdomen had no effect on mechanical or thermal hyperalgesia, suggesting that the effects we observed were local rather than systemic. We conclude that prostaglandins, probably prostaglandin E1 or E2, contribute to the peripheral mechanisms underlying hyperalgesia following nerve injury. These data provide further evidence that inflammatory mediators contribute to neuropathic pain, and may warrant further study of peripherally administered non-steroidal anti-inflammatory drugs as a possible treatment for such pain in patients.
Syriatowicz
J P
JP
School of Anatomy, University of New South Wales, Sydney, Australia.
Hu
D
D
Walker
J S
JS
Tracey
D J
DJ
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007839:Functional Laterality; D006614:Hindlimb; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D000077239:Meloxicam; D011453:Prostaglandins / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D013843:Thiazines; D013844:Thiazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D000077239:Meloxicam; D007213:Indomethacin