Degenerative IVD conditioned media and acidic pH sensitize sensory neurons to cyclic tensile strain.
Degenerative IVD conditioned media and acidic pH sensitize sensory neurons to cyclic tensile strain.
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退化的IVD条件培养基和酸性pH使感觉神经元对循环拉伸应变敏感。
DOI：
10.1002/jor.24682
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发表时间：
2021-06
影响因子：
2.8
通讯作者：
Bowles, Robby D.
中科院分区：
文献类型：
--
作者：
Stover, Joshua D.;Lawrence, Brandon;Bowles, Robby D.
腰痛是全世界导致残疾的主要原因之一。退行性间盘(IVD)环境中含有病理性高水平的炎性细胞因子和酸性pH，推测通过使伤害性神经元对健康患者不会感到疼痛的刺激敏感，从而导致背痛。我们假设退行性IVD环境通过使伤害性神经元对机械负荷敏感来驱动间盘源性疼痛。为了验证这一假说，我们开发了一个体外模型，该模型有助于研究退行性IVD环境、支配IVD的伤害性神经元和机械负荷之间的相互作用，并识别退行性IVD诱导伤害性神经元敏化的潜在机制。在我们的模型中，大鼠背根神经节(DRG)神经元种植在牛纤维环组织上，暴露于退化的IVD条件培养液和/或酸性pH中，并在钙成像测量DRG感觉神经元活动的过程中受到循环拉伸应变(1 Hz；1%-6%应变)。利用这一模型，我们证明了退行性IVD条件培养液和退行性IVD酸性pH水平均可诱导伤害感受性神经元的激活，以响应生理水平的机械应变。此外，白介素6(IL-6)介导了退行性IVD条件培养液诱导的伤害性神经元的激活。这些结果表明，IL-6介导了退行性IVD诱导的神经元对机械负荷的敏化，并进一步确立了IL-6作为治疗间盘源性疼痛的潜在治疗靶点。数据进一步表明，退行性IVD环境包含多个神经元敏化途径(IL-6，pH)，这些通路可能有助于间盘源性疼痛。
Low back pain is among the leading causes of disability worldwide. The degenerative intervertebral disc (IVD) environment contains pathologically high levels of inflammatory cytokines and acidic pH hypothesized to contribute to back pain by sensitizing nociceptive neurons to stimuli that would not be painful in healthy patients. We hypothesized that the degenerative IVD environment drives discogenic pain by sensitizing nociceptive neurons to mechanical loading. To test this hypothesis, we developed an in vitro model that facilitated the investigation of interactions between the degenerative IVD environment, nociceptive neurons innervating the IVD and mechanical loading of the disc; and, the identification of the underlying mechanism of degenerative IVD induced nociceptive neuron sensitization. In our model, rat dorsal root ganglia (DRG) neurons were seeding onto bovine annulus fibrosus tissue, exposed to degenerative IVD conditioned media and/or acidic pH, and subjected to cyclic tensile strain (1 Hz; 1%–6% strain) during measurement of DRG sensory neuron activity via calcium imaging. Using this model, we demonstrated that both degenerative IVD conditioned media and degenerative IVD acidic pH levels induced elevated nociceptive neuron activation in response to physiologic levels of mechanical strain. In addition, interleukin 6 (IL-6) was demonstrated to mediate degenerative IVD conditioned media induced elevated nociceptive neuron activation. These results demonstrate IL-6 mediates degenerative IVD induced neuron sensitization to mechanical loading and further establishes IL-6 as a potential therapeutic target for the treatment of discogenic pain. Data further suggests the degenerative IVD environment contains multiple neuron sensitization pathways (IL-6, pH) that may contribute to discogenic pain.
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影响因子：
3.7
作者：
Mair N;Benetti C;Andratsch M;Leitner MG;Constantin CE;Camprubí-Robles M;Quarta S;Biasio W;Kuner R;Gibbins IL;Kress M;Haberberger RV
通讯作者：
Haberberger RV
影响因子：
4.9
作者：
Le Maitre, Christine Lyn;Hoyland, Judith Alison;Freemont, Anthony J
通讯作者：
Freemont, Anthony J
DOI：
10.1302/0301-620x.75b4.8331126
发表时间：
1993-07-01
影响因子：
--
作者：
MIYATSU, M;ATSUTA, Y;WATAKABE, M
通讯作者：
WATAKABE, M
影响因子：
3
作者：
Burke, JG;Watson, RWG;Fitzpatrick, JM
通讯作者：
Fitzpatrick, JM
DOI：
10.1016/j.spinee.2013.01.041
发表时间：
2013-03
期刊：
The spine journal : official journal of the North American Spine Society
影响因子：
--
作者：
Mayer JE;Iatridis JC;Chan D;Qureshi SA;Gottesman O;Hecht AC
通讯作者：
Hecht AC