title: Cyclooxygenase-2 inhibitor SC-236 attenuates mechanical allodynia following nerve root injury in rats.
abstract: Low back pain is a common problem, affecting approximately two-thirds of the adult population. Of these individuals, a significant percentage will exhibit symptoms of radicular pain or sciatica. The purpose of this study was to determine the effect of one systemic (2 mg/kg) or intrathecal (0.2 mg/kg) dose of a selective cyclooxygenase-2 inhibitor (SC-236) in decreasing existing mechanical allodynia in a rat model of radiculopathy. Gait disturbance and mechanical allodynia (increased response to non-noxious von Frey monofilament stimuli) were assessed daily until the rats were killed 7 days after surgery. Robust mechanical allodynia developed in the rats in all groups except for those in the sham group by day 1 after surgery. Mechanical allodynia was significantly lower in the rats that received the systemic or the intrathecal dose of SC-236 than in those in the vehicle control group (analysis of variance followed by Bonferroni multiple comparison test, p = 0.002). The intrathecal drug route of administration produced greater attenuation in allodynia than the systemic dose, supporting a central mechanism of action of the cyclooxygenase-2 inhibitor (p = 0.002). The hypothesis that cyclooxygenase-2 is involved in spinal nociceptive processing after a nerve root injury was supported by this study. In addition, these data support continued basic science research to further elucidate central inflammatory processes that follow nerve root injury.
authors.affiliation: Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, USA. joyce.a.deleo@dartmouth.edu
authors.forename: T A
authors.initials: TA
authors.lastname: Deleo
authors.forename: H
authors.initials: H
authors.lastname: Hashizume
authors.forename: M D
authors.initials: MD
authors.lastname: Rutkowski
authors.forename: T N
authors.initials: TN
authors.lastname: Weinstein
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003714:Denervation / Q000009:adverse effects; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D017116:Low Back Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D011720:Pyrazoles / Q000494:pharmacology*; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides