In vivo evaluation of the hippocampal glutamate, GABA and the BDNF levels associated with spatial memory performance in a rodent model of neuropathic pain.
Patients with chronic pain usually suffer from learning and memory impairment which may significantly decrease their quality of life. Despite laboratory and clinical studies, the mechanism underlying this memory impairment remains elusive. We evaluated the effect of chronic pain on the glutamate and GABA levels and BDNF expression in the CA1 region of hippocampus as a possible explanation for memory impairment related to neuropathic pain.



In this respect, 30 male rats were randomly allocated to 3 groups as control, sham and neuropathic. Neuropathic pain was induced by a chronic constriction injury of the sciatic nerve (CCI) and mechanical allodynia and the spatial memory was assessed using the Von Frey filaments and Morris water maze respectively. To determine the potential mechanisms, the in vivo extracellular levels of glutamate and γ-aminobutyric acid (GABA) were measured by microdialysis and the brain-derived neurotrophic factor (BDNF) expression was determined by using western blots technique in the hippocampus on days 14 and 21 post-CCI.



We showed that CCI impaired spatial learning and memory in Morris water maze (MWM) task. BDNF expression level and glutamate concentration significantly decreased in rats with chronic constriction injury of the sciatic nerve (P<0.001, F=7.3, F=23.23). In addition, GABA increased in hippocampal CA1 region (P<0.001, F=39.2) when the pain threshold was minimum. Nevertheless, these changes reversed while pain was relieved spontaneously.



Chronic pain induced by constriction of the sciatic nerve impairs the spatial learning and memory function in rats. This effect exerts through the increase in GABA concentration and decrease in the glutamate and BDNF levels in the CA1 region of the hippocampus.
Neuroscience Research Center of Kerman, University of Medical Science, Kerman, Iran.
S
S
Saffarpour
Neuroscience Research Center of Kerman, University of Medical Science, Kerman, Iran.
M
M
Shaabani
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
N
N
Naghdi
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
M
M
Farahmandfar
Physiology Research Center, Department of Physiology, Iran University of Medical Sciences, Tehran, Iran.
A
A
Janzadeh
Physiology Research Center, Department of Physiology, Iran University of Medical Sciences, Tehran, Iran. Electronic address: nasirinezhad.f@iums.ac.ir.
F
F
Nasirinezhad
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology*; D017551:Microdialysis; D009437:Neuralgia / Q000150:complications* / Q000473:pathology*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
Brain-derived neurotrophic factor (BDNF); Chronic constriction injury (CCI); Glutamate; Hippocampus; Morris water maze task; Neuropathic pain; Spatial memory; γ-Aminobutyric acid (GABA)