Changes of Neuropathic Pain in nNOS Knock-out Mice
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신경손상 후 척수나 후근신경절에서 NO 생성 변화가 이질통(allodynia)에 관여하는 것으로 알려져 있다. 반면 nNOS의 발현이 이질통의 유발과 유지에 관여하지 않는다는 보고도 있다. 본 연구에서는 감각신경계통의 nNOS의 발현이 신경병증성 통증에서의 역할을 규명하고자 하였다. 정상조군 및 nNOS 결핍 생쥐에서 말초신경 손상 후 von Frey 및 아세톤 테스트를 시행하였으며, 이들 쥐에 nNOS 억제제를 투여하여 통증의 변화를 확인하였다. nNOS 결핍 생쥐에서는 말초신경 손상 후 정상대조군 생쥐보다 물리적 이질통이 약간 감소하였다. 정상대조군에서는 nNOS 억제제인 L-NAME 투여에 의해 물리적 이질통이 약간 감소하였다. 반면에, gabapentin은 정상대조 군 및 nNOS 결핍 생쥐 모두에서 신경병증성 통증(물리적 및 냉 이질통)을 현저히 감소시켰다. 이상의 결과는 생쥐의 신경병증성 모델에서 감각신경계의 nNOS의 발현이 물리적 이질통의 유발과 유지에 일부 관여하고 있음을 보여준다.
Abstract
Changes in nitric oxide production in spinal cord or dorsal root ganglion have been known to contribute to allodynia after nerve injury. However, regulation of nNOS expression was also reported not to be responsible for the development and/or maintenance of neuropathic allodynia. The aim of this study was to elucidate role of nNOS expression in the sensory nervous system in neuropathic pain. Von Frey and acetone tests were performed in a model of peripheral neuropathy, ligation of 5th lumbar and 6th lumbar spinal nerves, in wild type and nNOS (-/-) mice. The effect of nNOS inhibitor was evaluated in neuropathic pain behavior in the mice. Mechanical allodynia was slightly reduced in nNOS (-/-) mice compared with wild type mice after peripheral neuropathy. nNOS inhibitor, L-NAME, reduced minimally mechanical allodynia, not cold allodynia, but gabapentin reduced remarkably neuropathic pain behavior (mechanical and cold allodynia) in both wild type and nNOS (-/-) mice. These results suggested that nNOS expression in the sensory nervous system may be partially associated with development and/or maintenance of mechanical allodynia in a mouse model of peripheral neuropathy.
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