Role of Cyclooxygenase Isoforms in Peripheral Neuropathic Pain Model

In human, the neuropathic pain evoked by nerve injury includes severe mechanical allodynia and hyperalgesia in the region where the nerve innervates. The mechanism of the development of neuropathic pain was not yet well known and the solution for it was not also elucidated. The ligation of L5 spinal nerve entering the dorsal root ganglia developed mechanical hyperalgesia within 1 day, and showed similar symptoms as in human with neuropathic pain. We investigated whether COX isoforms, rate-limiting enzymes that synthesize the prostaglandins, were 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 intraperitoneally 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 and COX protein in the dorsal root ganglia (DRG), entering sensory information into the spinal cord were significantly increased. The immunoreactivity of COX-2 and tumor necrosis factor α (TNFα) were also increased in the lesioned spinal nerve, which were closely correlated with neuropatic mechanical hyperalgesia. The data thus suggests that the COX isoforms in the nervous system might participate 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 TNFα immunoreactivity of the nerve with inflammation was significantly increased, whereas the COX-2 immunoreactivity was significantly changed in only 3 days after inflammation. The expression of COX-2 and TNFα in neuritis was little correlated with the neuritis-induced pain behavior. The results might suggest that the expression of TNFα and COX-2 in neuropathic pain is related not with inflammation, but with neuropathic pain mechanism. In conclusion, the COX-2 and TNFα 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.

Author dc:creator

• 이, 우용

Contributors dc:contributor

• 백, 은주
• 대학원 의학과
• 200124294

• neuropathic pain
• cyclooxygenase
• prostaglandin
• spinal nerve
• 신경병증 통증
• 척수신경

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000279
000000000279

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/2291