Intraarticular pretreatment with ketamine and memantine could prevent arthritic pain: relevance to the decrease of spinal c-fos expression in rats.
To determine whether intraarticular pretreatment with N-methyl-D-aspartic (NMDA) receptor antagonist ketamine or memantine currently used in humans has prophylactic analgesia in arthritic pain, we examined the effects of their intraarticular injection before carrageenan injection into the knee joint on pain-related behavior and spinal c-Fos expression in rats. Injection of ketamine (0.2 mg and 1 mg) or memantine (0.1 mg, 0.2 mg, and 1 mg) into the knee joint, but not the abdominal cavity, immediately before carrageenan injection (2%, 40 microL) significantly prevented pain-related behavior. The intraarticular injection of ketamine (1 mg) or memantine (0.2 mg) also suppressed c-Fos expression in the laminae I-II and laminae V-VI at the L3-4 spinal level. Subsequent statistical analyses revealed that the degree of the spinal c-Fos expression was correlated with the extent of the pain-related behavior. These results suggest that peripheral administration of NMDA receptor antagonists has prophylactic analgesic effects in arthritic pain, which might be associated with the decrease of central nociceptive signaling. Because ketamine and memantine are currently used in humans and considered clinically safe, they may have therapeutic value in the treatment of joint pain.
*Department of Physiology, College of Medicine and Neuroscience Research Institute, Medical Science Research Center, Korea University, Seoul; and †Department of Obstetrics & Gynecology, Gil Medical Center, Gachon Medical School, Inchon, South Korea.
Guo Hua
GH
Zhang
Sun Seek
SS
Min
Kyu Sang
KS
Lee
Seung Keun
SK
Back
Seong Jun
SJ
Yoon
Young Wook
YW
Yoon
Yang In
YI
Kim
Heung Sik
HS
Na
Seung Kil
SK
Hong
Hee Chul
HC
Han
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002351:Carrageenan; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016474:Weight-Bearing / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D002351:Carrageenan; D008559:Memantine