Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats

Yeo, Ji‐Youn; Jung, Hyuk; Lee, Hye-Rim

doi:10.1155/2017/7394626

Cited by 8 publications

(6 citation statements)

References 30 publications

(38 reference statements)

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“…Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating neuropathic pain condition that usually affects the limb and is not accompanied with a clinically verifiable nerve injury [1]. CRPS-I usually develops after an initial injury, which includes ischemia, soft tissue trauma, surgery, or fractures to the extremity [2,3]. CRPS-I can develop into chronic pain state that severely affects the patient's life quality [4].…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

Chen

Yin

et al. 2020

J Neuroinflammation

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Background Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition. The mechanisms of CRPS-I still remain poorly understood. We aim to explore expression profiles of genes relevant to pain and neuroinflammation mechanisms involved in CRPS-I. Methods The rat chronic post-ischemic pain (CPIP) model that mimics human CRPS-I was established. RNA-sequencing (RNA-Seq), qPCR, Western blot, immunostaining, and pharmacological studies were used for profiling gene changes in ipsilateral spinal cord dorsal horn (SCDH) of CPIP model rat and further validation. Results CPIP rats developed persistent mechanical allodynia in bilateral hind paws, accompanied with obvious glial activation in SCDH. RNA-Seq identified a total of 435 differentially expressed genes (DEGs) in ipsilateral SCDH of CPIP rats. qPCR confirmed the expression of several representative genes. Functional analysis of DEGs identified that the most significantly enriched biological processes of upregulated genes include inflammatory and innate immune response. We further identified NLRP3 inflammasome expression to be significantly upregulated in SCDH of CPIP rats. Pharmacological blocking NLRP3 inflammasome reduced IL-1β overproduction, glial activation in SCDH as well as mechanical allodynia of CPIP rats. Conclusion Our study revealed that immune and inflammatory responses are predominant biological events in SCDH of CPIP rats. We further identified NLRP3 inflammasome in SCDH as a key contributor to the pain and inflammation responses in CPIP rats. Thus, our study provided putative novel targets that may help to develop effective therapeutics against CRPS-I.

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Section: Introductionmentioning

confidence: 99%

Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

Chen

Yin

et al. 2020

J Neuroinflammation

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“…By means of this model, several mechanisms, including central glial activation, central pain sensitization, reactive oxygen species increase and activation of peripheral TRPA1, etc. have been proposed to contribute to CRPS-I (Klafke et al, 2016; Kim et al, 2017;Yeo et al, 2017; Tang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1

Wang

et al. 2019

Front. Pharmacol.

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Complex regional pain syndrome type 1 (CRPS-I) is a debilitating pain condition that significantly affects life quality of patients. It remains a clinically challenging condition and the mechanisms of CRPS-I have not been fully elucidated. Here, we investigated the involvement of TRPV1, a non-selective cation channel important for integrating various painful stimuli, in an animal model of CRPS-I. A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. TRPV1 expression was significantly increased in hind paw tissue and small to medium-sized dorsal root ganglion (DRG) neurons of CPIP rats. CPIP rats showed increased TRPV1 current density and capsaicin responding rate in small-sized nociceptive DRG neurons. Local pharmacological blockage of TRPV1 with the specific antagonist AMG9810, at a dosage that does not produce hyperthermia or affect thermal perception or locomotor activity, effectively attenuated thermal and mechanical hypersensitivity in bilateral hind paws of CPIP rats and reduced the hyperexcitability of DRG neurons induced by CPIP. CPIP rats showed bilateral spinal astrocyte and microglia activations, which were significantly attenuated by AMG9810 treatment. These findings identified an important role of TRPV1 in mediating thermal and mechanical hypersensitivity in a CRPS-I animal model and further suggest local pharmacological blocking TRPV1 may represent an effective approach to ameliorate CRPS-I.

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“…Glutamate and glutathione also contribute to the measured Glx peak. Treatment with the latter has been shown to attenuate mechanical allodynia in a rat model of centralized pain analogous to complex regional pain syndrome [83]. In patients with FMS, augmentation of glutathione, a prevalent antioxidant, with coenzyme Q10, reduced clinical pain and increased pressure pain threshold in addition to reducing neural activity [67].…”

Section: Discussionmentioning

confidence: 99%

Altered Neurotransmitter Ratio in the Prefrontal Cortex is Associated with Pain in Fibromyalgia Syndrome

Bishop

Faerman

Geoly

et al. 2021

Preprint

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The central mechanisms underlying fibromyalgia syndrome (FMS) remain undetermined. The dorsolateral prefrontal cortex (DLPFC) is particularly relevant to FMS because it is implicated in cognitive, affective, and top-down pain regulation. Imbalances in excitatory (Glutamate) and inhibitory (Gamma aminobutyric acid; GABA) neurochemicals may play a critical role in the pathophysiology of the condition and more generally in homeostatic function within cortical circuits. Although the balance of excitation and inhibition are intrinsically linked no investigations to date have investigated the E/I ratio in FMS. Thus, the primary objective of this study was to determine whether the E/I ratio in the DLPFC is altered in participants with FMS compared to healthy controls using magnetic resonance spectroscopy. Additionally, we examined the relationship between E/I ratio and pain metrics. We hypothesized that the E/I ratio within the DLPFC would be altered in participants with FMS compared to controls and, secondly, that E/I ratio would be associated with both clinical pain and thermal pain sensitivity. The Brief Pain Inventory (BPI) self-assessment was used to evaluate pain severity and impact on physical functioning and acute pain sensitivity was determined via quantitative sensory testing to define thermal (heat) pain threshold and tolerance. Our results revealed an elevation in the E/I ratio in FMS compared to controls. A positive relationship between E/I ratio and thermal pain sensitivity measures was identified in the FMS cohort. Collapsing across groups, there was a positive relationship between E/I ratio and BPI score. These findings suggest that dysfunction in the balance between excitation and inhibition within cognitive brain circuitry may play a role in pain processing in FMS.

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Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats

Cited by 8 publications

References 30 publications

Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1

Altered Neurotransmitter Ratio in the Prefrontal Cortex is Associated with Pain in Fibromyalgia Syndrome

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