CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice

Kong, Yan-Fang; Sha, Wei‐Lin; Wu, Xiaobo; Zhao, Lin-Xia; Ma, Lingjie; Gao, Yong‐Jing

doi:10.1007/s12264-020-00608-1

Cited by 34 publications

(22 citation statements)

References 50 publications

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“…12 Inflammatory pain is a type of chronic pathologic pain that decreases a patient's quality of life and causes considerable economic losses to society. [13][14][15][16][17][18] In our present study, we used the classic CFA-induced model, involving a subcutaneous injection of CFA into the left hind paw of rats, to study the mechanisms of chronic inflammatory pain. Successfully induced rats in the CFA group showed significantly reduced activity and obvious redness and swelling in their left hind paw compared with the contralateral right hind paw.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3-TRPV1 signaling regulates chronic inflammatory pain in rats

Zhang

Peng

et al. 2022

Mol Pain

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Osteoarthritis (OA) is a common osteoarthropathy with chronic inflammatory pain as the core symptom in middle-aged and elderly people. LncRNA MEG3 (Maternally expressed gene 3) is involved in the development of OA via regulation of angiogenesis, which causes the activation and overexpression of transient receptor potential vanilloid type-1 (TRPV1). In this study, we investigated the mechanism of MEG3-TRPV1 signaling in chronic inflammatory pain (CIP) of rat model. Chronic inflammatory pain was modeled using subcutaneous microinjection of complete Freund’s adjuvant (CFA) into the left hind paw of rats. We showed that TRPV1 mRNA and protein were significantly increased, while MEG3 mRNA was significantly decreased, in the DRG and SDH of CFA-induced rats. In addition, intrathecal injection of MEG3-overexpressing lentivirus significantly downregulated TRPV1 expression and alleviated chronic inflammatory pain in CFA-induced rats. Treatment with a TRPV1 antagonist also significantly relieved chronic inflammatory pain in CFA-induced rats. In general, our results reveal that MEG3 alleviates chronic inflammatory pain by downregulating TRPV1 expression. These findings may provide new therapeutic targets in the treatment of patients with OA.

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Section: Discussionmentioning

confidence: 99%

LncRNA MEG3-TRPV1 signaling regulates chronic inflammatory pain in rats

Zhang

Peng

et al. 2022

Mol Pain

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“…Meanwhile, this study also demonstrates the importance of other biomarkers (e.g., CXCL10) and clinical variables (e.g., operation duration, anesthesia duration and BMI) in patients after hepatectomy, although they were not entered into the SVM model implemented by the machine learning algorithm. In mice with spinal nerve ligation (SNL), CXCL10-activated CXCR3 was found to mediate p38 and ERK activation in DRG neurons and enhance neuronal excitability, which contributed to the maintenance of neuropathic pain (11). BMI was also reported to be a crucial risk factor for CPSP in cardiac surgery because overweighting or obesity increased the technical difficulty and might expose patients to prolonged retraction giving rise to CPSP (32).…”

Section: Figurementioning

confidence: 99%

“…But with the emergence of new neural-inflammatory pathways, the inflammatory mediators' profiles need to be updated. Recently, C-X-C motif chemokine ligand 10 (CXCL10) (11) levels is found to exacerbates pain in mice. Matrix metalloproteases (MMPs) (12), dedicating to generate neuroinflammation, are implicated in the development of pain.…”

Section: Introductionmentioning

confidence: 99%

Identifying an optimal machine learning model generated circulating biomarker to predict chronic postoperative pain in patients undergoing hepatectomy

Hong

et al. 2023

Front. Surg.

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Chronic postsurgical pain (CPSP) after hepatectomy is highly prevalent and challenging to treat. Several risk factors have been unmasked for CPSP after hepatectomy, such as acute postoperative pain. The current secondary analysis of a clinical study sought to extend previous research by investigating more clinical variables and inflammatory biomarkers as risk factors for CPSP after hepatectomy and sifting those strongly related to CPSP to build a reliable machine learning model to predict CPSP occurring. Participants included 91 adults undergoing hepatectomy who was followed 3 months postoperatively. Twenty-four hours after surgery, participants completed numerical rating scale (NRS) grading and blood sample collecting. Three months after surgery, participants also reported whether CPSP occurred through follow-up. The Random Forest and Support Vector Machine models were conducted to predict pain outcomes 3 months after surgery. The results showed that the SVM model had better performance in predicting CPSP which consists of acute postoperative pain (evaluated by NRS) and matrix metalloprotease 3 (MMP3) level. What's more, besides traditional cytokines, several novel inflammatory biomarkers like C-X-C motif chemokine ligand 10 (CXCL10) and MMP2 levels were found to be closely related to CPSP and a novel spectrum of inflammatory biomarkers was created. These findings demonstrate that the SVM model consisting of acute postoperative pain and MMP3 level predicts greater chronic pain intensity 3 months after hepatectomy and with this model, intervention administration before CPSP occurs may prevent or minimize CPSP intensity successfully.

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“…Chemokines, released by activated neurons, astrocytes or macrophages or in spinal cord/dorsal root ganglia after chronic constriction injury, may interact with key receptors to trigger other cells to express pain mediators and, produce a cascade amplifier network (Zhang et al 2017). Emerging evidence has revealed that CXCR3 can specifically bind to its ligand, C-X-C motif chemokine ligand 10 (CXCL10), a chemokine attracting immunocyte, to form a CXCL10-CXCR3 axis that has been implicated in inflammation, itch, and neuropathic pain (Chen et al 2019;Jing et al 2018;Ju et al 2021;Kong et al 2021). In addition, CXCR3 alone has been reported to induce neuropathic pain in anterior cingulate cortex (Qin et al 2020).…”

Section: )mentioning

confidence: 99%

“…Importantly, by using the SwissTargetPrediction system (http://www.swisstargetprediction.ch/index.php), C-X-C motif chemokine receptor 3 (CXCR3) was predicted as a candidate molecule mediated by Bel. Chemokines and receptors have been involved in the development of chronic pain, and increased CXCR3 signaling in dorsal root ganglion has been recently found to exacerbate neuropathic pain in mice (Kong et al 2021).…”

Section: Introductionmentioning

confidence: 99%

β-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor

Dai

Zeng

Deng

et al. 2022

Can. J. Physiol. Pharmacol.

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β-elemene (Bel) is a sesquiterpene compound has shown potential in the antinociceptive treatment. This study focused on the function of Bel in neuropathic pain relief in mice. A murine model with spared nerve injury (SNI) was established and treated with Bel. The paw withdrawal thresholds in response to mechanical and thermal stimulations were examined using von Frey filaments. The L4-L6 spinal dorsal horn tissue samples were collected for histological examination. Bel treatment reduced the sensitivities of model mice to mechanical and thermal stimulations, and it inhibited activation of microglia and the secretion of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in tissues. Bel treatment reduced the expression of nociceptor excitatory NMDAR whereas enhanced the expression of nociceptor inhibitory GABAA receptor to relieve the nociception of mice. CXCR3 was a downstream molecule mediated by Bel. Either overexpression of CXCR3 or downregulation of GABAA receptor in the tissues aggravated the neuropathic pain in SNI mice which was initially relieved by Bel. In conclusion, this study suggested that Bel might serve as a drug for nociception management by inhibiting CXCR3 and upregulating GABAA receptor. This study may offer novel insights into the field of neuropathic pain relief.

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CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice

Cited by 34 publications

References 50 publications

LncRNA MEG3-TRPV1 signaling regulates chronic inflammatory pain in rats

LncRNA MEG3-TRPV1 signaling regulates chronic inflammatory pain in rats

Identifying an optimal machine learning model generated circulating biomarker to predict chronic postoperative pain in patients undergoing hepatectomy

β-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor

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