Differential sensitization of silent nociceptors to low pH stimulation by prostaglandin E2 in human volunteers
Differential sensitization of silent nociceptors to low pH stimulation by prostaglandin E2 in human volunteers
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DOI：
10.1002/ejp.532
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Schmelz, M.
中科院分区：
文献类型：
--
作者：
Namer, B.;Schick, M.;Schmelz, M.
背景炎症介质激活和增敏伤害感受器。组织酸中毒与低pH值为5.5往往伴随着炎症，并可以增强炎性疼痛和sensitization. Methods动作电位从单一的机械反应（CM）和机械不敏感（CMi）的C-伤害性感受器的腓神经皮束在健康志愿者的显微神经造影术记录。将含有和不含前列腺素E2（PGE 2）的低pH溶液两次（间隔约5 min）注射到C-纤维感受野的两个点中。热阈值的C-纤维之前和之后得到的每个inject.ResultsInjections的低pH值的解决方案立即诱导CM伤害感受器的阶段性反应，而CMi纤维响应后，延迟几秒钟的持续响应。更多的CMi纤维比CM纤维表现出持续放电后，低pH值注射，但持续时间和强度的反应，第一次低pH值注射没有显着差异。重复后，pH值的反应的持续时间和强度增加了两倍以上，CMi纤维。此外，pH和PGE 2的组合应用仅在CMi纤维中敏化反应。相比之下，热激活阈值敏化低pH值和PGE 2在两个fiberclass.ConclusionsOur结果证实伤害感受器类独立的热敏化PGE 2这可能是介导的瞬时受体电位vanilloid 1磷酸化。然而，在低pH/PGE 2刺激后，人类中延长和增加的疼痛反应似乎主要依赖于CMi纤维，而CM伤害感受器似乎对阶段性反应至关重要。
BackgroundInflammatory mediators activate and sensitize nociceptors. Tissue acidosis with low pH of 5.5 often accompanies inflammation and could enhance inflammatory pain and sensitization.MethodsAction potentials from single mechano-responsive (CM) and mechano-insensitive (CMi) C-nociceptors of cutaneous fascicles of the peroneal nerve in healthy volunteers were recorded by microneurography. Low pH solutions with and without prostaglandin E2 (PGE2) were injected twice (with an interval of approximately 5min) into two spots of the receptive fields of C-fibres. Heat thresholds of the C-fibres were obtained before and after each injection.ResultsInjections of the low pH solutions immediately induced phasic responses in CM nociceptors, whereas CMi fibres responded after a delay of several seconds with a sustained response. More CMi fibres than CM fibres showed ongoing discharge after low pH injection, but the duration and intensity of the responses to the first low pH injection did not differ between them. Upon repetition, duration and intensity of the pH responses increased more than twofold in CMi fibres only. Furthermore, combined application of pH and PGE2 sensitized the response in CMi fibres only. In contrast, heat activation thresholds were sensitized by the combination of low pH and PGE2 in both fibre classes.ConclusionsOur results confirm nociceptor class independent heat sensitization by PGE2 which is probably mediated by transient receptor potential vanilloid 1 phosphorylation. However, prolonged and increased pain responses in humans upon low pH/PGE2 stimulation appear to be primarily dependent on CMi fibres, whereas CM nociceptors appear crucial for phasic responses.