Dorsi Michael J, Chen Lun, Murinson Beth B, Pogatzki-Zahn Esther M, Meyer Richard A, Belzberg Allan J
Department of Neurosurgery, The Johns Hopkins University, School of Medicine, 5-181 Meyer Building, Baltimore, MD 21287, USA Department of Neurology, The Johns Hopkins University, School of Medicine, 5-181 Meyer Building, Baltimore, MD 21287, USA Applied Physics Laboratory, Johns Hopkins University, Laurel, MD, USA Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany.
Pain. 2008 Feb;134(3):320-334. doi: 10.1016/j.pain.2007.06.030. Epub 2007 Aug 27.
Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma. We describe a new animal model of neuroma pain in which the neuroma was located in a position that is accessible to mechanical testing and outside of the innervation territory of the injured nerve. This allowed testing of pain in response to mechanical stimulation of the neuroma (which we call neuroma tenderness) independent of pain due to mechanical hyperalgesia. In the tibial neuroma transposition (TNT) model, the posterior tibial nerve was ligated and transected in the foot just proximal to the plantar bifurcation. Using a subcutaneous tunnel, the end of the ligated nerve was positioned just superior to the lateral malleolus. Mechanical stimulation of the neuroma produced a profound withdrawal behavior that could be distinguished from the hyperalgesia that developed on the hind paw. The neuroma tenderness (but not the hyperalgesia) was reversed by local lidocaine injection and by proximal transection of the tibial nerve. Afferents originating from the neuroma exhibited spontaneous activity and responses to mechanical stimulation of the neuroma. The TNT model provides a useful tool to investigate the differential mechanisms underlying the neuroma tenderness and mechanical hyperalgesia associated with neuropathic pain.
周围神经损伤可能导致疼痛性神经瘤的形成。在患者中,触诊神经瘤上方的组织会在受损神经的分布区域引发感觉异常/感觉障碍。以往的神经性疼痛动物模型主要关注远离损伤部位产生的机械性痛觉过敏和异常性疼痛,而不是直接刺激神经瘤引起的疼痛。我们描述了一种新的神经瘤疼痛动物模型,其中神经瘤位于可进行机械测试的位置且在受损神经的支配区域之外。这使得能够独立于机械性痛觉过敏引起的疼痛,测试对神经瘤机械刺激的疼痛反应(我们称之为神经瘤压痛)。在胫神经瘤移位(TNT)模型中,胫后神经在足底分叉近端的足部被结扎并切断。通过皮下隧道,将结扎神经的末端置于外踝上方。对神经瘤的机械刺激产生了强烈的退缩行为,这与后爪出现的痛觉过敏不同。局部注射利多卡因和近端切断胫神经可逆转神经瘤压痛(但不能逆转痛觉过敏)。源自神经瘤的传入神经表现出自发性活动以及对神经瘤机械刺激的反应。TNT模型为研究与神经性疼痛相关的神经瘤压痛和机械性痛觉过敏的不同机制提供了一个有用的工具。