Medullary pain facilitating neurons mediate allodynia in headache-related pain.
Medullary pain facilitating neurons mediate allodynia in headache-related pain.
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DOI：
10.1002/ana.21537
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发表时间：
2009-02
影响因子：
11.2
通讯作者：
Porreca, Frank
中科院分区：
文献类型：
--
作者：
Edelmayer, Rebecca M.;Vanderah, Todd W.;Majuta, Lisa;Zhang, En-Tan;Fioravanti, Beatriz;De Felice, Milena;Chichorro, Juliana G.;Ossipov, Michael H.;King, Tamara;Lai, Josephine;Kori, Shashi H.;Nelsen, Andrew C.;Cannon, Keri E.;Heinricher, Mary M.;Porreca, Frank
开发和验证由硬脑膜炎症引发的与头痛相关的疼痛的皮肤异常性痛模型。探讨头外异常性疼痛的神经机制。将炎症介质（IM）通过预先植入的套管注入未麻醉大鼠的硬脑膜，并对面部和后肢的感觉阈值进行表征。IM引起强烈的面部和后爪异常性疼痛，在3小时内达到高峰。这些效应让人想起偏头痛或其他原发性头痛患者的皮肤异位性疼痛，并被临床用于治疗偏头痛的药物逆转，包括舒马曲坦、萘普生和cgrp拮抗剂。与临床观察一致，NK-1拮抗剂不影响异常性疼痛。在确定了面部和后爪异常痛症作为头痛相关异常痛症的有用动物替代物后，我们接下来表明，在吻侧腹内侧髓质（RVM）阻断疼痛促进过程会干扰其表达。布比卡因，破坏假定的疼痛促进神经元或阻断胆囊收缩素受体可以预防或显著减轻im引起的异常性疼痛。电生理研究证实了IM后促进疼痛的RVM ON细胞的激活和RVM OFF细胞的短暂抑制。与硬脑膜刺激相关的面部和后爪异常痛是与原发性头痛（包括偏头痛）相关的疼痛的有用替代，并且可能在机制上用于开发新的头痛治疗策略。数据还表明，颅和颅外皮肤异痛症的表达需要激活RVM的下行促进，并且与头痛疾病相关的异痛症的脑干产生器一致。
To develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches. To explore neural mechanisms underlying cephalic and extracephalic allodynia. Inflammatory mediators (IM) were applied to the dura of unanesthetized rats via previously implanted cannulas and sensory thresholds of the face and hindpaws were characterized. IM elicited robust facial and hindpaw allodynia which peaked within 3 hr. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in treatment of migraine, including sumatriptan, naproxen, and a CGRP-antagonist. Consistent with clinical observations the allodynia was unaffected by an NK-1 antagonist. Having established facial and hindpaw allodynia as a useful animal surrogate of headache-associated allodynia, we next showed that blocking pain-facilitating processes in the rostral ventromedial medulla (RVM) interfered with its expression. Bupivacaine, destruction of putative pain-facilitating neurons or block of cholecystokinin receptors prevented or significantly attenuated IM-induced allodynia. Electrophysiological studies confirmed activation of pain-facilitating RVM ON cells and transient suppression of RVM OFF cells following IM. Facial and hindpaw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for development of novel therapeutic strategies for headache pain. The data also demonstrate the requirement for activation of descending facilitation from the RVM for the expression of cranial and extracranial cutaneous allodynia and are consistent with a brainstem generator of allodynia associated with headache disorders.
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影响因子：
5
作者：
Dodick, David;Silberstein, Stephen
通讯作者：
Silberstein, Stephen
影响因子：
11.2
作者：
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Goadsby, PJ
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