Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats.
Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats.
复制标题
受体亚型介导神经性路易斯大鼠疼痛行为和异位放电的肾上腺素敏感性。
DOI：
10.1152/jn.1999.81.5.2226
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Chung,JM
中科院分区：
文献类型：
--
作者：
Lee,DH;Liu,X;Kim,HT;Chung,K;Chung,JM
受体亚型介导神经病刘易斯大鼠痛行为和异位放电的肾上腺素敏感性。 我们试图在刘易斯品系大鼠节段性脊髓损伤（SSI）模型中鉴定负责交感神经（肾上腺素能）依赖性神经病理性疼痛的α-肾上腺素能受体（α-AR）亚型。选择该模型是因为我们先前的研究表明，这种情况下的疼痛行为对全身注射酚妥拉明（PTL）（一种通用的α-AR阻滞剂）特别敏感。我们研究了特异性α1-和α2-AR阻断剂对1）机械性异常性疼痛的行为体征，2）在体内条件下记录的异位放电，和3）在体外设置中记录的异位放电的影响。在L5和L 6脊神经的紧密结扎后一周，足缩回的爪的机械阈值急剧降低;我们将这种变化解释为机械性异常性疼痛的迹象。全身注射PTL（α1-和α2-AR拮抗剂的混合物）或特拉唑嗪（TRZ，α1-AR拮抗剂）可显著缓解机械性异常性疼痛体征，但各种α2-AR拮抗剂（咪唑克生、萝芙木碱或育亨宾）均不能缓解，表明α1-AR是机械性异常性疼痛体征的部分介质。持续的异位放电记录损伤传入神经束的L5背根的神经病大鼠在体内记录设置。PTL或TRZ腹腔注射后，持续放电率显着降低，但咪唑克生没有。此外，通过使用体外记录设置，自发活动被记录在其中脊神经被预先结扎的节段中的被戏弄的背根纤维。应用肾上腺素灌注浴增强持续放电。这种诱发的活动被阻断预处理TRZ，但不与咪唑克生。这项研究表明，在刘易斯神经病大鼠中，机械性异常性疼痛的行为体征和受损传入神经的异位放电部分地由涉及α1-AR的机制介导。这些结果表明，在刘易斯品系大鼠神经病理性疼痛的交感神经依赖性是由AR α 1亚型介导的。
Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of α-adrenergic receptor (α-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general α-AR blocker. We examined the effects of specific α1- and α2-AR blockers on1) behavioral signs of mechanical allodynia,2) ectopic discharges recorded in the in vivo condition, and3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed α1- and α2-AR antagonist) or terazosin (TRZ, an α1-AR antagonist) but not by various α2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the α1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving α1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the α1subtype of AR.