Differential antinociceptive effects induced by a selective cyclooxygenase-2 inhibitor (SC-236) on dorsal horn neurons and spinal withdrawal reflexes in anesthetized spinal rats.
The aim of present study was to examine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor SC-236 (4 mg/kg) on the simultaneous responsiveness of spinal wide-dynamic range (WDR) neurons and single motor units (SMUs) from gastrocnemius soleus muscles to mechanical stimuli (pressure and pinch) and repeated suprathreshold (1.5xT, the intensity threshold) electrical stimuli with different frequencies (3 Hz, 20 Hz) under normal conditions and bee venom (BV, 0.2 mg/50 microl)-induced inflammation and central sensitization. During normal conditions, the responses of SMUs, but not WDR neurons, to mechanical and repeated electrical stimuli (3 Hz, wind-up) were depressed by systemic administration of SC-236 as well as its vehicle (100% dimethyl sulfoxide (DMSO)). The after-discharges of both the WDR neurons and the simultaneously recorded SMUs after electrical stimuli with 20 Hz were markedly depressed only by SC-236, indicating that the mechanisms underlying the generation of the C-fiber mediated late responses and the after-discharges may be different. The enhanced responsiveness of both WDR neurons and SMUs to mechanical pressure stimuli (allodynia) and pinch stimuli (hyperalgesia) in the BV experiments was apparently depressed by SC-236, but not its vehicle. For electrical stimulation, the enhanced late responses and after-discharges, but not early responses, of both the WDR neurons and the simultaneously recorded SMUs were markedly depressed only by SC-236. This indicates that different central pharmacological mechanisms underlie the generation of these enhanced early, late responses, and after-discharges during BV-induced inflammation. The data suggest that the COX-2 inhibitor SC-236 apparently depress the activities of both spinal cord dorsal horn neuron and spinal withdrawal reflex during BV-induced sensitization, indicating that COX-2 plays an important role in the maintenance of central sensitization.
You
H J
HJ
Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Fredrik Bajers Vej 7D-3, DK-9220, Aalborg, Denmark. lan@smi.auc.dk
Mørch
C D
CD
Chen
J
J
Arendt-Nielsen
L
L
D000200:Action Potentials; D000758:Anesthesia; D000818:Animals; D001514:Bee Venoms / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004576:Electromyography / Q000379:methods; D004594:Electrophysiology; D006614:Hindlimb / Q000294:innervation; D006930:Hyperalgesia; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D001514:Bee Venoms; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides