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Resveratrol-decreased hyperalgesia mediated by the P2X7 receptor in gp120-treated rats.

ABSTRACT: Background Chronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120 (gp120) can directly cause hyperalgesia by stimulating primary sensory afferent nerves. The P2X7 receptor in the dorsal root ganglia (DRG) is closely related to neuropathic and inflammatory pain. In this study, we aimed to explore the effect of resveratrol (RES) on gp120-induced neuropathic pain that is mediated by the P2X7 receptor in the rat DRG. Results Mechanical hyperalgesia in rats treated with gp120 was increased compared with that in the sham group. The P2X7 expression levels in rats treated with gp120 were higher than those in the sham group. Co-localization of the P2X7 receptor and glial fibrillary acidic protein (GFAP, a marker of satellite glial cells [SGCs]) in the DRG SGCs of the gp120 group exhibited more intense staining than that of the sham group. RES decreased the mechanical hyperalgesia and P2X7 expression levels in gp120 treatment rats. Co-localization of the P2X7 receptor and GFAP in the gp120+ RES group was significantly decreased compared to the gp120 group. RES decreased the IL-1? and TNF-? receptor (R) expression levels and ERK1/2 phosphorylation levels as well as increased IL-10 expression in the DRG of gp120-treated rats. Whole cell clamping demonstrated that RES significantly inhibited adenosine triphosphate-activated currents in HEK293 cells that were transfected with the P2X7 plasmid. Conclusions RES relieved mechanical hyperalgesia in gp120-treated rats by inhibiting the P2X7 receptor.

SUBMITTER: Wu B

PROVIDER: S-EPMC5453631 | biostudies-literature | 2017 Jan-Dec

REPOSITORIES: biostudies-literature

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Resveratrol-decreased hyperalgesia mediated by the P2X<sub>7</sub> receptor in gp120-treated rats.

Wu Bing B Ma Yucheng Y Yi Zhihua Z Liu Shuangmei S Rao Shenqiang S Zou Lifang L Wang Shouyu S Xue Yun Y Jia Tianyu T Zhao Shanhong S Shi Liran L Li Lin L Yuan Huilong H Liang Shangdong S

Molecular pain 20170101

Background Chronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120 (gp120) can directly cause hyperalgesia by stimulating primary sensory afferent nerves. The P2X<sub>7</sub> receptor in the dorsal root ganglia (DRG) is closely related to neuropathic and inflammatory pain. In this study, we aimed to explore the effect of resveratrol (RES) on gp120-induced neuropathi ...[more]

PMID: 28554250

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Project description:Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown.We employed a Sprague-Dawley rat of collagenase-induced ICH in the present study. The time course of H2S content and the spatial expression of cystathionine-β-synthase (CBS) after ICH, the effects of endogenous and exogenous H2S after ICH, the effects of endogenous and exogenous H2S on NLRP3 inflammasome activation under P2X7 receptor (P2X7R) overexpression after ICH, and the involvement of the P2X7R in the mechanism by which microglia-derived H2S prevented NLRP3 inflammasome activation were investigated.We found ICH induced significant downregulation of endogenous H2S production in the brain, which may be the result of decreasing in CBS, the predominant cerebral H2S-generating enzyme. Administration of S-adenosyl-L-methionine (SAM), a CBS-specific agonist, or sodium hydrosulfide (NaHS), a classical exogenous H2S donor, not only restored brain and plasma H2S content but also attenuated brain oedema, microglial accumulation and neurological deficits at 1 day post-ICH by inhibiting the P2X7R/NLRP3 inflammasome cascade. Endogenous H2S production, which was derived mainly by microglia and above treatments, was verified by adenovirus-overexpressed P2X7R and in vitro primary microglia studies.These results indicated endogenous H2S synthesis was impaired after ICH, which plays a pivotal role in the P2X7R/NLRP3 inflammasome-associated neuroinflammatory response in the pathogenesis of secondary brain injury. Maintaining appropriate H2S concentrations in the central nervous system may represent a potential therapeutic strategy for managing post-ICH secondary brain injury and associated neurological deficits.

Project description:Although opioids are potent analgesics, a consequence of chronic opioid use is hyperalgesia during withdrawal, which may contribute to opioid misuse. Dynorphin, the endogenous ligand of κ-opioid receptors (KORs), is upregulated in opioid-dependent rats and in animal models of chronic pain. However, the role of KORs in opioid withdrawal-induced hyperalgesia remains to be determined. We hypothesized that KOR antagonism would reverse opioid withdrawal-induced hyperalgesia in opioid-dependent rats. Male and female Wistar rats received daily injections of heroin (2-6 mg/kg, SC) and were tested for mechanical sensitivity in the electronic von Frey test 4-6 h into withdrawal. Female rats required significantly more heroin than male rats to reach comparable levels of both heroin-induced analgesia and hyperalgesia (6 mg/kg vs. 2 mg/kg). Once hyperalgesia was established, we tested the effects of the KOR antagonists nor-binaltorphimine (norBNI; 30 mg/kg, SC) and 5'-guanidinonaltrindole (5'GNTI; 30 mg/kg, SC). When the animals continued to receive their daily heroin treatment (or saline treatment in the repeated saline group) five times per week throughout the experiment, both KOR antagonists reversed heroin withdrawal-induced hyperalgesia. The anti-hyperalgesia effect of norBNI was more prolonged in males than in females (14 days vs. 7 days), whereas 5'GNTI had more prolonged effects in females than in males (14 days vs. 4 days). The behavioral effects of 5'GNTI coincided with higher 5'GNTI levels in the brain than in plasma when measured at 24 h, whereas 5'GNTI did not reverse hyperalgesia at 30 min posttreatment when 5'GNTI levels were higher in plasma than in the brain. Finally, we tested the effects of 5'GNTI on naloxone-induced and spontaneous signs of opioid withdrawal and found no effect in either male or female rats. These findings indicate a functional role for KORs in heroin withdrawal-induced hyperalgesia that is observed in rats of both sexes.

Dataset Information

Resveratrol-decreased hyperalgesia mediated by the P2X7 receptor in gp120-treated rats.

Publications

Resveratrol-decreased hyperalgesia mediated by the P2X<sub>7</sub> receptor in gp120-treated rats.

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