title: Upregulation of glutamatergic transmission in anterior cingulate cortex in the diabetic rats with neuropathic pain.
abstract: 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.
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: Lihuaendo01@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D013311:Streptozocin; D009435:Synaptic Transmission; D014110:Touch; D015854:Up-Regulation; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D000099221:Protein Kinase C zeta
chemical_list: D018698:Glutamic Acid; D011493:Protein Kinase C; D017470:Receptors, Glutamate; D013311:Streptozocin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000099221:Protein Kinase C zeta
keywords: Anterior cingulate cortex; Diabetic neuropathic pain; Glutamatergic transmission; Protein kinase M ζ