当在生理性机械或无痛化学暴露之前发生时，生理性关节面囊伸展可诱发疼痛并上调背根神经节中的基质金属蛋白酶-3。

Physiologic facet capsule stretch can induce pain & upregulate matrix metalloproteinase-3 in the dorsal root ganglia when preceded by a physiological mechanical or nonpainful chemical exposure.

作者信息

Singh Sagar, Kartha Sonia, Bulka Ben A, Stiansen Nicholas S, Winkelstein Beth A

机构信息

Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104, USA.

Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104, USA.

出版信息

Clin Biomech (Bristol). 2019 Apr;64:122-130. doi: 10.1016/j.clinbiomech.2018.01.009. Epub 2018 Jan 31.

DOI:10.1016/j.clinbiomech.2018.01.009

PMID:29523370

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6067996/

Abstract

BACKGROUND

Neck pain from cervical facet loading is common and induces inflammation and upregulation of nerve growth factor (NGF) that can sensitize the joint afferents. Yet, the mechanisms by which these occur and whether afferents can be pre-conditioned by certain nonpainful stimuli are unknown. This study tested the hypothesis that a nonpainful mechanical or chemical insult predisposes a facet joint to generate pain after a later exposure to typically nonpainful distraction.

METHODS

Rats were exposed to either a nonpainful distraction or an intra-articular subthreshold dose of NGF followed by a nonpainful distraction two days later. Mechanical hyperalgesia was measured daily and C6 dorsal root ganglia (DRG) tissue was assayed for NGF and matrix metalloproteinase-3 (MMP-3) expression on day 7.

FINDINGS

The second distraction increased joint displacement and strains compared to its first application (p = 0.0011). None of the initial exposures altered behavioral sensitivity in either of the groups being pre-conditioned or in controls; but, sensitivity was established in both groups receiving a second distraction within one day that lasted until day 7 (p < 0.024). NGF expression in the DRG was increased in both groups undergoing a pre-conditioning exposure (p < 0.0232). Similar findings were observed for MMP-3 expression, with a pre-conditioning exposure increasing levels after an otherwise nonpainful facet distraction.

INTERPRETATION

These findings suggest that nonpainful insults to the facet joint, when combined, can generate painful outcomes, possibly mediated by upregulation of MMP-3 and mature NGF.

摘要

背景

颈椎小关节负荷引起的颈部疼痛很常见，会诱发炎症并导致神经生长因子（NGF）上调，进而使关节传入神经敏感化。然而，这些现象发生的机制以及传入神经是否能通过某些非疼痛性刺激进行预处理尚不清楚。本研究检验了以下假设：非疼痛性机械或化学损伤会使小关节在随后暴露于通常为非疼痛性的牵张刺激后更容易产生疼痛。

方法

将大鼠暴露于非疼痛性牵张刺激或关节内阈下剂量的NGF中，两天后再给予非疼痛性牵张刺激。每天测量机械性痛觉过敏，并在第7天检测C6背根神经节（DRG）组织中NGF和基质金属蛋白酶-3（MMP-3）的表达。

结果

与首次应用相比，第二次牵张刺激增加了关节位移和应变（p = 0.0011）。在预处理组或对照组中，任何初始暴露都未改变行为敏感性；但是，在接受第二次牵张刺激的两组中，一天内均建立了敏感性，并持续到第7天（p < 0.024）。在接受预处理暴露的两组中，DRG中的NGF表达均增加（p < 0.0232）。MMP-3表达也有类似发现，在非疼痛性小关节牵张刺激后，预处理暴露会增加其水平。