Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain.
A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT) clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and antihyperalgesic effects of IT clonidine were examined post-treatment in a rat model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia. Using a chronic model of spinal cord dialysis, we examined the effect of the adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the development of chronic pain and assessed the antinociceptive effects and mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups receiving IT clonidine in discrete doses of 1, 10 or 50 microg, 3 or 24 hr post-inflammation. Measurement of total NOx (NO + NO2- + NO3-) was used to determine NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed using a radiant heat thermal hyperalgesia model. CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation. A dose-dependent suppression of thermal hyperalgesia and spinal NO release was observed after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain model suggests that clonidine's spinal antihyperalgesic mechanisms act through inhibition of spinal NO release.
Lin
C R
CR
Anesthesiology Research Laboratory, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung Hsien, Taiwan.
Chuang
Y C
YC
Cheng
J T
JT
Wang
C J
CJ
Yang
L C
LC
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology; D019329:Idazoxan / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009187:Myelitis / Q000139:chemically induced* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester; D019329:Idazoxan