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  • 08월 28일 16시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

Decline of morphine efficacy over time following nerve injury in a rat model

2008년 8월 21일 11시 33분 29초
금19G1심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
금 09시 : 20분
의약화학 - Recent Drug Development of Chronic Pain and Neuropathic Pain
저자 및
고려대학교 의과대학 생리학교실, Korea
Morphine has been considered as a potent analgesic, but its analgesic efficacy in neuropathic pain is highly controversial. In addition, glial cell activation is likely to contribute to neuropathic pain as well as opioid tolerance. In present study, we examined whether the morphine efficacy in neuropathic pain changes over time following nerve injury, and whether this change is related to spinal glial responses. To meet these aims, we evaluated the morphine (1 or 2 mg/kg, i.p.) efficacy in alleviating mechanical allodynia in rats at different times after partial injury of tail-innervating nerves; 2 and 16 weeks after the nerve injury. Morphine efficacy was more prominent in the 2W group than in the 16W group, suggesting that morphine efficacy reduced as the pain progresses. To address the involvement of spinal glia in the reduction of morphine efficacy, we investigated whether suppression of spinal glia could reverse the diminished morphine efficacy in the 16W group. While single treatment of morphine (1 mg/kg, i.p.) or AV411 (2.5 μg/rat, i.t.), a glia-specific phosphodiesterase inhibitor, did not attenuate mechanical allodynia, the coinjection of morphine (1 mg/kg, i.p.) with intrathecal AV411 (2.5 g/rat) significantly suppressed mechanical allodynia. Our data suggest that morphine efficacy to neuropathic pain reduced as the pain progresses and the reduction may be involved, in part, in spinal glial responses after peripheral nerve injury.