Li Weifang, Wang Peng, Li Hua
Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China.
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China.
Neurosci Lett. 2014 May 7;568:29-34. doi: 10.1016/j.neulet.2014.03.038. Epub 2014 Mar 28.
Peripheral neuropathic pain is a common complication in the diabetic patients, and the underlying central mechanism remains unclear. Forebrain anterior cingulate cortex (ACC) is critically involved in the supraspinal perception of physical and affective components of noxious stimulus and pain modulation. Excitatory glutamatergic transmission in the ACC extensively contributed to the maintenance of negative affective component of chronic pain. The present study examined the adaptation of glutamatergic transmission in the ACC in rats with diabetic neuropathic pain. Injection with streptozotocin (STZ) induced hyperglycemia, thermal hyperalgesia and mechanical allodynia in the rats. In these rats, significant enhanced basal glutamatergic transmission was observed in the ACC neurons. The increased presynaptic glutamate release and enhanced conductance of postsynaptic glutamate receptors were also observed in the ACC neurons of these modeled rats. Increased phosphorylation of PKMζ, but not the expression of total PKMζ, was also observed in the ACC. Microinjection of PKMζ inhibitor ZIP into ACC attenuated the upregulation of glutamate transmission and painful behaviors in STZ-injected rats. These results revealed a substantial central sensitization in the ACC neurons in the rodents with diabetic neuropathic pain, which may partially underlie the negative affective components of patients with diabetic neuropathic pain.
外周神经病理性疼痛是糖尿病患者常见的并发症，其潜在的中枢机制尚不清楚。前脑前扣带回皮质（ACC）在脊髓上对有害刺激的躯体和情感成分的感知以及疼痛调节中起关键作用。ACC中的兴奋性谷氨酸能传递广泛地参与了慢性疼痛负面情感成分的维持。本研究检测了糖尿病性神经病理性疼痛大鼠ACC中谷氨酸能传递的适应性变化。注射链脲佐菌素（STZ）可诱导大鼠出现高血糖、热痛觉过敏和机械性异常性疼痛。在这些大鼠中，观察到ACC神经元的基础谷氨酸能传递显著增强。在这些模型大鼠的ACC神经元中还观察到突触前谷氨酸释放增加和突触后谷氨酸受体电导增强。在ACC中还观察到PKMζ的磷酸化增加，但总PKMζ的表达未增加。向ACC微量注射PKMζ抑制剂ZIP可减弱STZ注射大鼠中谷氨酸传递的上调和疼痛行为。这些结果揭示了糖尿病性神经病理性疼痛啮齿动物的ACC神经元中存在显著的中枢敏化，这可能是糖尿病性神经病理性疼痛患者负面情感成分的部分原因。
