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TECHNOLOGY, COMPUTING, AND SIMULATION

Intraarticular Pretreatment with Ketamine and Memantine Could Prevent Arthritic Pain: Relevance to the Decrease of Spinal c-Fos Expression in Rats

Guo Hua Zhang, MD PhD^*, Sun Seek Min, PhD^*, Kyu Sang Lee, MS^*, Seung Keun Back, MS^*, Seong Jun Yoon, MD PhD, Young Wook Yoon, MD PhD^*, Yang In Kim, PhD, Heung Sik Na, MD PhD^*, Seung Kil Hong, MD PhD^*, and Hee Chul Han, MD PhD^*

*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

Address correspondence and reprint requests to Hee Chul Han, MD, PhD, Department of Physiology, College of Medicine, Korea University, 126-1 Anam-dong 5 ga, Sungbuk-gu, Seoul 136-705, Korea. Address e-mail to heehan{at}korea.ac.kr

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 µL) 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.

IMPLICATIONS: This study demonstrated that peripheral pretreatment with ketamine and memantine suppressed both arthritic pain-related behavior and spinal c-Fos expression. These results indicate that both ketamine and memantine have prophylactic analgesia and provide support for their potential use as peripheral analgesics for joint pain.

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