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.
Anesthesiology Research Laboratory, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung Hsien, Taiwan.
C R
CR
Lin
Y C
YC
Chuang
J T
JT
Cheng
C J
CJ
Wang
L C
LC
Yang
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