Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats
Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats
复制标题
DOI：
10.1152/jn.2002.87.6.2726
复制
发表时间：
2002-06-01
影响因子：
2.5
通讯作者：
Pan, HL
中科院分区：
文献类型：
--
作者：
Chen, SR;Pan, HL
糖尿病性神经性疼痛通常被认为是由周围神经病变引起的。中枢神经系统在这种病理状态的参与还没有得到很好的记录。脊髓背角神经元超敏反应的发生与创伤性神经损伤引起的神经病理性疼痛有关。在本研究中，我们确定了脊髓丘脑束（STT）神经元的功能变化及其与糖尿病神经病理性疼痛的相关性。腹腔注射链脲佐菌素诱导大鼠糖尿病模型。通过对施加到后爪的压力、辐射热和von Frey细丝的撤回反应来评估痛觉过敏和异常性疼痛。记录麻醉大鼠腰髓STT神经元的单位活动。本实验观察了糖尿病大鼠和正常大鼠STT神经元对机械刺激和热刺激的反应以及对吗啡的敏感性。12只糖尿病大鼠在注射链脲佐菌素后2周内出现机械性痛觉超敏和痛觉过敏，但不出现热性痛觉过敏，并持续≥ 7周。与正常动物的32个STT神经元相比，糖尿病大鼠的37个STT神经元显示出更高的自发放电活动和更大的感受野。此外，糖尿病大鼠的STT神经元表现出较低的阈值和机械刺激的反应增强。静脉注射吗啡2.5mg/kg可明显抑制12只非糖尿病大鼠STT神经元对伤害性刺激的反应。然而，吗啡对STT神经元诱发反应的这种抑制作用在14只糖尿病动物中减弱。这项电生理研究提供了新的信息，脊髓背角投射神经元的超敏性的发展可能与糖尿病引起的神经病理性疼痛症状密切相关。此外，吗啡对糖尿病STT神经元诱发反应的抑制作用减弱可能是其在这种临床形式的神经性疼痛中镇痛功效降低的原因。
Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for greater than or equal to7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.