Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury.
Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury.
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DOI：
10.1186/s13293-017-0163-5
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发表时间：
2018-01-03
影响因子：
7.9
通讯作者：
Jankowski MP
中科院分区：
文献类型：
--
作者：
Ross JL;Queme LF;Lamb JE;Green KJ;Jankowski MP
慢性疼痛状况在女性中更普遍，但大多数关于疼痛产生机制的临床前研究都是使用雄性动物进行的。此外，而第III和IV组伤害性肌肉传入引起中枢敏感化更有效地比他们的皮肤对应，少是已知的这个关键群体的肌肉伤害性感受器。在这里，我们比较了未受伤的男性和女性的个别肌肉传入的生理。然后，我们表征短暂性缺血和再灌注损伤（I/R）的分子，生理和行为效应，我们在男性和女性中广泛研究的模型。使用离体肌肉/神经/背根神经节（DRG）/脊髓记录制备比较了对机械、热和化学刺激的响应特性和表型。损伤相关变化的分析也通过测定诱发和自发性疼痛相关行为以及受影响肌肉和DRG的mRNA表达来进行。对每项测量进行适当的方差分析和事后检验（需要时进行错误发现率校正）。女性有更多的机械敏感的肌肉传入，并表现出更大的机械和热反应比男性。与I/R，两种性别显示较少的细胞响应无害的代谢物溶液（ATP，乳酸，质子），并降低机械阈值在个人传入;然而，女性也具有改变热反应，这可能与性别相关的基因表达的变化在受影响的DRG。无论如何，两种性别在I/R诱导的疼痛样行为中表现出相似的增加。在这里，我们说明了一个独特的现象，其中离散的，性别依赖性机制的初级肌肉传入敏感缺血性损伤后的周边可能是性别之间的类似行为变化的基础。此外，虽然第三组和第四组肌肉传入功能完全发达，差异机制的敏感性表现在性成熟之前。因此，这项研究表明迫切需要进一步探索整个生命周期中传入功能的性别差异，以用于开发适当的针对性疼痛治疗。本文的在线版本（10.1186/s13293-017-0163-5）包含补充材料，可供授权用户使用。
Chronic pain conditions are more prevalent in women, but most preclinical studies into mechanisms of pain generation are performed using male animals. Furthermore, whereas group III and IV nociceptive muscle afferents provoke central sensitization more effectively than their cutaneous counterparts, less is known about this critical population of muscle nociceptors. Here, we compare the physiology of individual muscle afferents in uninjured males and females. We then characterize the molecular, physiological, and behavioral effects of transient ischemia and reperfusion injury (I/R), a model we have extensively studied in males and in females. Response properties and phenotypes to mechanical, thermal, and chemical stimulation were compared using an ex vivo muscle/nerve/dorsal root ganglia (DRG)/spinal cord recording preparation. Analyses of injury-related changes were also performed by assaying evoked and spontaneous pain-related behaviors, as well as mRNA expression of the affected muscle and DRGs. The appropriate analyses of variance and post hoc tests (with false discovery rate corrections when needed) were performed for each measure. Females have more mechanically sensitive muscle afferents and show greater mechanical and thermal responsiveness than what is found in males. With I/R, both sexes show fewer cells responsive to an innocuous metabolite solution (ATP, lactic acid, and protons), and lower mechanical thresholds in individual afferents; however, females also possess altered thermal responsiveness, which may be related to sex-dependent changes in gene expression within the affected DRGs. Regardless, both sexes show similar increases in I/R-induced pain-like behaviors. Here, we illustrate a unique phenomenon wherein discrete, sex-dependent mechanisms of primary muscle afferent sensitization after ischemic injury to the periphery may underlie similar behavioral changes between the sexes. Furthermore, although the group III and IV muscle afferents are fully developed functionally, the differential mechanisms of sensitization manifest prior to sexual maturity. Hence, this study illustrates the pressing need for further exploration of sex differences in afferent function throughout the lifespan for use in developing appropriately targeted pain therapies. The online version of this article (10.1186/s13293-017-0163-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/s1521-6942(03)00042-1
发表时间：
2003-08-01
影响因子：
5.2
作者：
Gran, JT
通讯作者：
Gran, JT
DOI：
10.1016/s0967-2109(02)00070-4
发表时间：
2002-12-01
期刊：
CARDIOVASCULAR SURGERY
影响因子：
--
作者：
Blaisdell, FW
通讯作者：
Blaisdell, FW
影响因子：
4
作者：
Gaskin, Darrell J.;Richard, Patrick
通讯作者：
Richard, Patrick
影响因子：
5.3
作者：
Doyle, Hillary H.;Eidson, Lori N.;Murphy, Anne Z.
通讯作者：
Murphy, Anne Z.
DOI：
10.1016/j.berh.2015.04.024
发表时间：
2015-02-01
影响因子：
5.2
作者：
Clauw, Daniel J.
通讯作者：
Clauw, Daniel J.