Preemptive effects of intrathecal cyclooxygenase inhibitor or nitric oxide synthase inhibitor on thermal hypersensitivity following peripheral nerve injury.
The present study provides an important implication for the management of chronic neuropathic pain, focusing on prostaglandin (PG) and nitric oxide (NO) in the spinal cord. To determine if spinally administered cyclooxygenase (COX) inhibitor or nitric oxide synthase (NOS) inhibitor had preemptive analgesia on thermal hypersensitivity induced by chronic constrictive nerve injury, Sprague-Dawley rats were chronically implanted with an intrathecal (i.t.) catheter. The left sciatic nerve was loosely ligated with 2-mm polyethylene tubing to produce painful mononeuropathy. Animals received tenoxicam (7.5, 15 or 30 micromol/10 microl, i.t.), NS-398 (15 or 30 micromol), or L-NAME (30, 150 or 300 micromol) immediately before the nerve injury, followed by daily injection extending into the four postoperative days. The hindpaw was immersed into a hot (42 degrees C, 44 degrees C and 46 degrees C) or cold (10 degrees C) water bath. The paw immersion test revealed significant thermal hyperalgesia and allodynia 5 day after nerve injury in vehicle control animals. Tenoxicam (7.5, 15 or 30 micromol) or L-NAME (30, 150 or 300 micromol) dose-dependently attenuated hyperalgesia and allodynia. Equimolar dose of NS-398 (15 or 30 micromol) also diminished these nociceptive behaviors. Higher dose of either drug primarily produced longer duration of inhibition. The inhibitory effect of tenoxicam (30 micromol) on hyperalgesia was more effective than that of an equimolar dose of NS-398 or L-NAME. These results demonstrated that intrathecally administered COX inhibitor or NOS inhibitor provides preemptive analgesia on thermal hypersensitivity following chronic constrictive nerve injury in rats.
Lui
Ping-Wing
PW
Department of Anesthesiology, Chang Gung Memorial Hospital and Chang Gung University, Linkou, Taiwan. pwlui@adm.cgmh.org.tw
Lee
Chen-Hwa
CH
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D009578:Nitrobenzenes / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013449:Sulfonamides / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester; C032801:tenoxicam