Exp Neurobiol 2005; 14(1): 11-20
Published online November 30, -0001
© The Korean Society for Brain and Neural Sciences
Eun Joo Baik1,2*, Kyungsoon Chung3, Woo Yong Lee4, Kyoung Ja Kwon1,2 and You-Na Jang1,2
1Department of Physiology, 2Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-749, 3Department of Anatomy and Neuroscience, University of Texas Medical Branch, Galveston, TX 77555-1069, 4Department of Anesthesia and Pain Medicine Sanggyepaik Hospital, Inje University, Seoul 139-707, Korea
Correspondence to: *To whom correspondence should be addressed.
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In human, the neuropathic pain by nerve injury evoked severe mechanical allodynia and hyperalgesia in the region where the nerve innervate. The mechanism of the development of neuropathic pain was not yet well known and the solution for neuropathic pain had been not established. The ligation of L5 spinal nerve entering the dorsal root ganglia developed mechanical hyperalgesia within 1 day, and showed similar symptoms as a human with neuropathic pain. We investigated whether COX isoforms, a rate-limiting enzyme synthesize the prostaglandins, in the nervous system was involved in the pain behavior of spinal nerve-ligated rats. After ligation of left L5 spinal nerve in anesthetized rats, the foot withdrawal thresholds to mechanical stimuli applied to the affected hind paw (mechanical thresholds) were decreased significantly indicating the development of mechanical hyperalgesia, and the mechanical hyperalgesia lasted for 5 weeks. Nimesulide (5 mg/kg), a selective COX-2 inhibitor intraperitoneously administered everyday alleviated significantly the mechanical hyperalgesia, however acetylsalicylic acid (5 mg/kg), a preferential COX-1 inhibitor did not significantly alleviate them. COX- isoforms mRNA in the dorsal root ganglia (DRG), entering sensory information into the spinal cord were significantly increased in time. The immunoreactivity of COX-2 were also increased in the lesioned spinal nerve, which were closely correlated with neuropatic mechanical hyperalgesia. The data thus suggest the COX isoforms in the nervous system might be participated in the transmission of neuropathic pain. We also investigated the involvement of inflammatatory reaction in the development of neuropathic pain using neuritis models. The maintenance of neuritis-induced pain, which was milder and shorter than neuropathic pain, was not affected by nimesulide though nimesulide could subside transiently the pain. The COX-2 immunoreactivity was significantly changed in only 3 days after inflammation. The expression of COX-2 in neuritis was little correlated with the neuritis-induced pain behavior. The results might be suggested the expression of COX-2 in neuropathic pain was not indicated according to inflammation, but their expression in the nervous system was implicated with chronic pain behavior. In conclusion, the COX-2 in neuropathic states probably plays an important role in the early development and maintenance of mechanical hyperalgesia in neuropathic-specific condition beyond the inflammatory states.
Keywords: neuropathic pain, cyclooxygenase, inflammarion