Capturing the aversive state of cephalic pain preclinically.
Capturing the aversive state of cephalic pain preclinically.
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DOI：
10.1002/ana.23922
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发表时间：
2013-08
影响因子：
11.2
通讯作者：
Porreca, Frank
中科院分区：
文献类型：
--
作者：
DeFelice, Milena;Eyde, Nathan;Dodick, David;Dussor, Gregory O.;Ossipov, Michael H.;Fields, Howard L.;Porreca, Frank
通过疼痛缓解奖励的行为评估对头痛进行临床前评估。将炎症介质（IM）或对照溶液应用于大鼠硬脑膜，以引起假定的头痛状态。在单独的动物组中使用后爪切口以模拟非头部手术后疼痛。给药系统或显微注射在头端腹内侧延髓（RVM），核（NAc）或头端前扣带皮层（rACC）。周围神经阻滞（PNB）产生的水平，并使用诱发的感觉刺激或条件性位置偏爱（CPP）的行为进行了评估。进行免疫组织化学和脑微透析测量。硬脑膜IM产生持久的全身性皮肤异常性疼痛（CA）。RVM利多卡因可产生CPP，选择性增加NAc c FOS和多巴胺（DA）的释放，CPP可被多巴胺能受体拮抗剂α-氟哌噻吨阻断。静脉注射α-CGRP（8-37）可产生选择性位置偏爱（CPP），并可选择性地诱发NAc多巴胺释放。预先损伤rACC或全身性舒马曲坦或αCGRP（8-37）治疗可消除IM治疗大鼠中RVM利多卡因诱导的CPP。在接受RVM利多卡因的IM治疗大鼠中，舒马曲坦治疗阻断NAc多巴胺释放。全身舒马曲坦并没有改变疼痛缓解诱导的CPP大鼠切口损伤。通过评估寻求缓解的动机行为，揭示大鼠的头部疼痛。疼痛的缓解激活多巴胺能奖赏通路，引起行为的负强化。临床上对偏头痛有效的药物选择性地缓解持续的头部疼痛，但不能缓解手术后的非头部疼痛。这些研究为探索偏头痛的病理生理学和发现新的头痛疗法提供了一个平台。
Preclinical evaluation of headache by behavioral assessment of reward from pain relief. Inflammatory mediators (IM) or control solutions were applied to the rat dura mater to elicit a presumed state of cephalic pain. Hindpaw incision was used in separate groups of animals to model non- cephalic post-surgical pain. Drugs were given systemically or microinjected within the rostral ventromedial medulla (RVM), nucleus accumbens (NAc) or rostral anterior cingulate cortex (rACC). Peripheral nerve block (PNB) was produced at the level of the popliteal fossa and behavior was assessed using evoked sensory stimuli or conditioned place preference (CPP). Immunohistochemistry and brain microdialysis measurements were performed. Dural IM produced long-lasting generalized cutaneous allodynia (CA). RVM lidocaine produced CPP, increased NAc c-FOS and dopamine (DA) release selectively in rats receiving dural IM; CPP was blocked by intra-NAc α-flupenthixol, a dopaminergic antagonist. Intravenous αCGRP(8-37) produced CPP and elicited NAc dopamine release selectively in rats with dural IM. Prior lesion of the rACC or treatment with systemic sumatriptan, or αCGRP(8-37) abolished RVM lidocaine-induced CPP in IM-treated rats. Sumatriptan treatment blocked NAc dopamine release in IM treated rats receiving RVM lidocaine. Systemic sumatriptan did not alter pain-relief induced CPP in rats with incisional injury. Cephalic pain was unmasked in rats by assessment of motivated behavior to seek relief. Relief of pain activates the dopaminergic reward pathway to elicit negative reinforcement of behavior. Medications clinically effective for migraine headache selectively elicit relief of ongoing cephalic, but not post-surgical, non-cephalic pain. These studies provide a platform for exploring migraine pathophysiology and for the discovery of new headache therapies.
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影响因子：
16.2
作者：
Baliki, Marwan N.;Geha, Paul Y.;Fields, Howard L.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
5
作者：
Dodick, David;Silberstein, Stephen
通讯作者：
Silberstein, Stephen
影响因子：
9.9
作者：
Ho, T. W.;Mannix, L. K.;Rapoport, A. M.
通讯作者：
Rapoport, A. M.
影响因子：
2.7
作者：
Laviolette, SR;Nader, K;van der Kooy, D
通讯作者：
van der Kooy, D
影响因子：
4.1
作者：
FOLTZ, EL;WHITE, LE
通讯作者：
WHITE, LE