Electroacupuncture Relieves CCI-Induced Neuropathic Pain Involving Excitatory and Inhibitory Neurotransmitters

Abstract

Neuropathic pain caused by peripheral tissue injuries to the higher brain regions still has no satisfactory therapy. Disruption of the balance of excitatory and inhibitory neurotransmitters is one of the underlying mechanisms that results in chronic neuropathic pain. Targeting neurotransmitters and related receptors may constitute a novel approach for treating neuropathic pain. We investigated the effects of electroacupuncture (EA) on chronic constriction injury- (CCI-) induced neuropathic pain. The mechanical allodynia and thermal hyperalgesia pain behaviors were relieved by 15 Hz EA but not by 2 and 50 Hz. These phenomena were associated with increasing γ-amino-butyric acid (GABA) receptors in the hippocampus and periaqueductal gray (PAG) but not N-methyl-D-aspartate receptors. Furthermore, excitatory neurotransmitter glutamate was decreased in the hippocampus and inhibitory neurotransmitter GABA was increased in the PAG under treatment with EA. These data provide novel evidence that EA modulates neurotransmitters and related receptors to reduce neuropathic pain in the higher brain regions. This suggests that EA may be a useful therapy option for treating neuropathic pain.

Electroacupuncture at Zusanli and at Neiguan characterized point specificity in the brain by metabolomic analysis

“…Metabolite sample preparation and derivatization. Rat tissue samples were processed with similar procedures as our previous work 33 . Cerebral cortex, hippocampus, and hypothalamus tissues were respectively homogenized using 1.0-mm zirconium oxide bead grinding with a ratio of 1 mg of tissue to 10 μL of ultrapure water and then centrifuged at 14,000 rpm for 10 min.…”

“…Liquid chromatography-mass spectrometry. Samples were analyzed by our previously established methods 33 . The liquid chromatography-mass spectrometry (LC-MS) system consisted of an ultraperformance liquid chromatography (UPLC) system (ACQUITY UPLC I-Class, Waters) and an ESI/APCI source of 4 kDa quadrupole time-of-flight mass spectrometer (Waters VION, Waters).…”

Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review

“…Since MAPKs significantly contribute to the development of hyperalgesia, the inhibition of any of the three pathways, namely the ERK, p38, and JNK pathways, can rescue inflammatory or neuropathic pain. Several studies have reported that 2- and 15-Hz EA can downregulate cerebral TRPV4 expression and attenuate chronic constriction injury (CCI)-induced neuropathic pain in an animal model [ 173 , 174 , 175 , 176 , 177 , 178 , 179 ]. Furthermore, Huang et al reported that EA modulates both excitatory and inhibitory neurotransmitters to relieve neuropathic pain in the higher brain regions [ 175 ].…”

“…Several studies have reported that 2- and 15-Hz EA can downregulate cerebral TRPV4 expression and attenuate chronic constriction injury (CCI)-induced neuropathic pain in an animal model [ 173 , 174 , 175 , 176 , 177 , 178 , 179 ]. Furthermore, Huang et al reported that EA modulates both excitatory and inhibitory neurotransmitters to relieve neuropathic pain in the higher brain regions [ 175 ]. The hippocampus plays an integral role in the transition from acute to chronic pain in the limbic system by activating NMDA receptors and subsequently prolonging acute nociceptive stimuli that continue activating the descending pathways of pain ( Figure 6 ).…”

Neuropathic pain syndrome in wistar rats at different stages of chronic brain epileptization (chemical kindling)

“…При этом увеличение эндогенных уровней глутамата и снижение уровней ГАМК или блокирование чувствительных к стрихнину глициновых рецепторов в инсулах коры животных контрольной группы приводило к существенному увеличению тепловой гиперальгезии и механической аллодинии [25]. Применение электроакупунктуры у крыс после лигирования седалищного нерва приводило к снижению механической аллодинии и термической гиперальгезии, которое, по мнению авторов, связано с увеличением экспрессии ГАМК А -рецепторов в гиппокампе и периакведуктальном сером веществе, со снижением уровня возбуждающего нейротрансмиттера глутамата в гиппокампе и повышением уровня тормозного нейротрансмиттера ГАМК в периакведуктальном сером веществе [31]. Эти результаты и данные других исследований [27,32] свидетельствуют о том, что нарушение баланса между возбуждающими и ингибирующими нейротрансмиттерами является ключевым в патогенезе как боли, так и эпилепсии.…”