title: Enhanced GABA action on the substantia gelatinosa neurons of the medullary dorsal horn in the offspring of streptozotocin-injected mice.
abstract: Peripheral neuropathy is a frequent complication of diabetes mellitus and a common symptom of neuropathic pain, the mechanism of which is complex and involves both peripheral and central components of the sensory system. The lamina II of the medullary dorsal horn, called the substantia gelatinosa (SG), is well known to be a critical site for processing of orofacial nociceptive information. Although there have been a number of studies done on diabetic neuropathy related to the orofacial region, the action of neurotransmitter receptors on SG neurons in the diabetic state is not yet fully understood. Therefore, we used the whole-cell patch clamp technique to investigate this alteration on SG neurons in both streptozotocin (STZ)-induced diabetic mice and offspring from diabetic female mice. STZ (200 mg/kg)-injected mice showed a small decrease in body weight and a significant increase in blood glucose level when compared with their respective control group. However, application of different concentrations of glycine, gamma-aminobutyric acid (GABA) and glutamate on SG neurons from STZ-injected mice did not induce any significant differences in inward currents when compared to their control counterparts. On the other hand, the offspring of diabetic female mice (induced by multiple injections of STZ (40 mg/kg) for 5 consecutive days) led to a significant decrease in both body weight and blood glucose level compared to the control offspring. Glycine and glutamate responses in the SG neurons of the offspring from diabetic female mice were similar to those of control offspring. However, the GABA response in SG neurons of offspring from diabetic female mice was greater than that of control offspring. Furthermore, the GABA-mediated responses in offspring from diabetic and control mice were examined at different concentrations ranging from 3 to 1,000 μM. At each concentration, the GABA-induced mean inward currents in the SG neurons of offspring from diabetic female mice were larger than those of control mice. These results demonstrate that SG neurons in offspring from diabetic mice are more sensitive to GABA compared to control mice, suggesting that GABA sensitivity may alter orofacial pain processing in offspring from diabetic female mice.
authors.affiliation: Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Hoang Thi Thanh
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Janardhan Prasad
authors.initials: JP
authors.lastname: Bhattarai
authors.affiliation: Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Soo Joung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Orthodontics, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Jeong Chae
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Chonbuk National University Hospital and School of Medicine, Jeonju, Republic of Korea. Electronic address: obgyn2001@hanmail.net.
authors.forename: Dong Hyu
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea. Electronic address: skhan@jbnu.ac.kr.
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Han
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D016640:Diabetes, Gestational / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005155:Facial Nerve Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005157:Facial Pain / Q000150:complications / Q000209:etiology; D005260:Female; D047109:Fetal Development; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006130:Growth Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology; D013311:Streptozocin; D013376:Substantia Gelatinosa / Q000378:metabolism*; D009435:Synaptic Transmission; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013311:Streptozocin; D005998:Glycine
keywords: Diabetes mellitus; GABA; Patch clamp; Streptozotocin; Substantia gelatinosa neuron