Effect of long-term ketamine administration on vocalization to paw pressure and on spinal wind-up activity in monoarthritic rats.
The antinociceptive effect of long-lasting ketamine administration (mini-osmotic pump) was studied in monoarthritic rats by using hindpaw pressure testing and wind-up measurement in a C-fiber reflex paradigm. Chronic ketamine induced antinociception in the monoarthritic paw and significantly suppressed mechanical hyperalgesia during the 14-day treatment period. The treatment also reduced C-reflex wind-up in the monoarthritic hindpaw. After pump removal, vocalization thresholds and spinal wind-up scores from the monoarthritic paw returned to control values, while hyperalgesia developed in the normal paw. Results suggest that ketamine upregulates NMDA receptors upon long-term administration, resulting in hyperalgesic response in the normal paw after drug withdrawal.
Pelissier
Teresa
T
Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Alvarez
Pedro
P
Hernández
Alejandro
A
D000700:Analgesics / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001170:Arthritis, Infectious / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D002908:Chronic Disease; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects; D012044:Regression Analysis; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D005620:Freund's Adjuvant