scholarly journals Ceftriaxone Relieves Trigeminal Neuropathic Pain Through Suppression of Spatiotemporal Synaptic Plasticity via Restoration of Glutamate Transporter 1 in the Medullary Dorsal Horn

2020 ◽  
Vol 14 ◽  
Author(s):  
Xiao Luo ◽  
Ting He ◽  
Yan Wang ◽  
Jiang-Lin Wang ◽  
Xue-Bin Yan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Synaptic Plasticity ◽  
Dorsal Horn ◽  
Glutamate Transporter ◽  
Trigeminal Neuropathic Pain ◽  
Medullary Dorsal Horn ◽  
Glutamate Transporter 1

scholarly journals Adenosine Monophosphate–activated Protein Kinase Regulates Interleukin-1β Expression and Glial Glutamate Transporter Function in Rodents with Neuropathic Pain

2015 ◽  
Vol 122 (6) ◽  
pp. 1401-1413 ◽  
Author(s):  
Dylan W. Maixner ◽  
Xisheng Yan ◽  
Mei Gao ◽  
Ruchi Yadav ◽  
Han-Rong Weng
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Adenosine Monophosphate ◽  
Interleukin 1Β ◽  
Spinal Dorsal ◽  
Glial Glutamate Transporter ◽  
Glutamate Transporter 1

Abstract Background: Neuroinflammation and dysfunctional glial glutamate transporters (GTs) in the spinal dorsal horn are implicated in the genesis of neuropathic pain. The authors determined whether adenosine monophosphate–activated protein kinase (AMPK) in the spinal dorsal horn regulates these processes in rodents with neuropathic pain. Methods: Hind paw withdrawal responses to radiant heat and mechanical stimuli were used to assess nociceptive behaviors. Spinal markers related to neuroinflammation and glial GTs were determined by Western blotting. AMPK activities were manipulated pharmacologically and genetically. Regulation of glial GTs was determined by measuring protein expression and activities of glial GTs. Results: AMPK activities were reduced in the spinal dorsal horn of rats (n = 5) with thermal hyperalgesia induced by nerve injury, which were accompanied with the activation of astrocytes, increased production of interleukin-1β and activities of glycogen synthase kinase 3β, and suppressed protein expression of glial glutamate transporter-1. Thermal hyperalgesia was reversed by spinal activation of AMPK in neuropathic rats (n = 10) and induced by inhibiting spinal AMPK in naive rats (n = 7 to 8). Spinal AMPKα knockdown (n = 6) and AMPKα1 conditional knockout (n = 6) induced thermal hyperalgesia and mechanical allodynia. These genetic alterations mimicked the changes of molecular markers induced by nerve injury. Pharmacological activation of AMPK enhanced glial GT activity in mice with neuropathic pain (n = 8) and attenuated glial glutamate transporter-1 internalization induced by interleukin-1β (n = 4). Conclusions: These findings suggest that enhancing spinal AMPK activities could be an effective approach for the treatment of neuropathic pain.

scholarly journals Astroglia in Medullary Dorsal Horn (Trigeminal Spinal Subnucleus Caudalis) Are Involved in Trigeminal Neuropathic Pain Mechanisms

2009 ◽  
Vol 29 (36) ◽  
pp. 11161-11171 ◽  
Author(s):  
A. Okada-Ogawa ◽  
I. Suzuki ◽  
B. J. Sessle ◽  
C.-Y. Chiang ◽  
M. W. Salter ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Pain Mechanisms ◽  
Trigeminal Neuropathic Pain ◽  
Medullary Dorsal Horn

Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons

Pain ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1082-1092 ◽  
Author(s):  
Zongqin Zhang ◽  
Xiaobao Ding ◽  
Zhiwei Zhou ◽  
Zhuang Qiu ◽  
Naihao Shi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Synaptic Plasticity ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Sirtuin 1 ◽  
Diabetic Neuropathic Pain ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

scholarly journals Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain

2021 ◽  
Author(s):  
Nuria García-Magro ◽  
Yasmina B. Martin ◽  
Pilar Negredo ◽  
Francisco Zafra ◽  
Carlos Avendaño
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Substantial Reduction ◽  
Negative Control ◽  
Infraorbital Nerve ◽  
Survival Times ◽  
Medullary Dorsal Horn ◽  
Inhibitory Circuitry ◽  
Basic Features ◽  
Heterogeneous Reduction

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse areas of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

scholarly journals Effects of Co-exposure to Lead and Manganese on Learning and Memory Deficits

2021 ◽  
Author(s):  
Rui-Li Guan ◽  
Tao Wang ◽  
Xiao-Ru Dong ◽  
Ke-Jun Du ◽  
Juan Li ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Real Life ◽  
Glutamate Transporter ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Metal Exposure ◽  
Combined Exposure ◽  
Sprague Dawley ◽  
Significant Difference ◽  
Glutamate Transporter 1

Abstract Background: Lead and manganese are common neurotoxins. However, individuals are subject to co-exposures in real life, and it is therefore important to study these metals in combination. Methods: Weaning Sprague-Dawley rats were given ad libitum access to drinking water solutions containing lead (100 ppm), manganese (2.5 mg/mL) or a mixture, and each treatment has its own minocycline (50 mg/Kg.d) supplement group. Results: The results showed a significant difference in spatial memory and the induction levels of hippocampal long-term potentiation (LTP) in all exposure groups when compared with controls. The combined exposure group exhibited the most pronounced effect when compared with each of the single metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5, accompanied by decreased expression levels of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Furthermore, the levels of the glutamate in the synaptic cleft increased significantly. When microglial activation was inhibited by minocycline, the activation of astrocytes, and the expression of GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment, the hippocampal LTP impairment and the cognitive injury were significantly alleviated in each of the exposure groups. Conclusions: These results suggest that combined exposure to lead and manganese can cause greater effects on cognition and synaptic plasticity when compared to single metal exposure groups. And the reason may involve in microglia abnormal activation leading to an excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and lead to perturbed cognition and synaptic plasticity.

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