Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats

Li, Li; Wu, Yong-Fang; Bai, Zhifeng; Hu, Yu-Yan; Li, Wenbin

doi:10.1080/01616412.2017.1281198

Cited by 12 publications

(5 citation statements)

References 38 publications

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“…NMDA receptor activation in the spinal cord is associated with the activation of microglia and astrocytes. 45 , 46 Esketamine is a dextral isomer of ketamine with stronger analgesic effects and it strongly blocks the NMDA receptor. 23 Moreover, esketamine has some affinity for opioid receptors, and it has effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and brain derived neurotrophic factor (BDNF) signaling; however, we did not find reports showing inhibition of central glial cell activation and signal pathways to explain esketamine’s analgesic effects.…”

Section: Discussionmentioning

confidence: 99%

Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats

Duan,

Zhu,

Zhang

et al. 2024

Mol Pain

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Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the development of various types of pain. However, the specific CIBP mechanisms remain unknown. Esketamine is a non-selective N-methyl-d-aspartic acid receptor (NMDA) inhibitor commonly used as an analgesic in the clinic, but its analgesic mechanism in bone cancer pain remains unclear. We used a tumor cell implantation (TCI) model and explored that CXCL12/CXCR4, p-MAPKs, and p-c-Jun were stably up-regulated in the spinal cord. Immunofluorescence images showed activated microglia in the spinal cord on day 14 after TCI and co-expression of CXCL12/CXCR4, p-MAPKs (p-JNK, p-ERK, p-p38 MAPK), and p-c-Jun in microglia. Intrathecal injection of the CXCR4 inhibitor AMD3100 reduced JNK and c-Jun phosphorylations, and intrathecal injection of the JNK inhibitor SP600125 and esketamine also alleviated TCI-induced pain and reduced the expression of p-JNK and p-c-Jun in microglia. Overall, our data suggest that the CXCL12/CXCR4-JNK-c-Jun signaling pathway of microglia in the spinal cord mediates neuronal sensitization and pain hypersensitivity in cancer-induced bone pain and that esketamine exerts its analgesic effect by inhibiting the JNK-c-Jun pathway.

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Section: Discussionmentioning

confidence: 99%

Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats

Duan,

Zhu,

Zhang

et al. 2024

Mol Pain

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“…NMDA is widely present in the central nervous system, and the NR2B subunit is mainly distributed in the forebrain and the spinal dorsal horn, which affects the development of pain transmission and chronic pain [29,30]. It has been suggested that NMDAR2B receptors are involved in the activation of glial cells in the spinal dorsal horn of neuropathic pain models [31].…”

Section: Discussionmentioning

confidence: 99%

Kilohertz High-Frequency Alternating Current Ameliorate Hyperalgesia and Inhibit the Glial Activation by Modulating TRPV1 and NMDAR2B Signaling Pathways in Chronic Constriction Injury of Sciatic Nerve Mice

Peng

Cheng

et al. 2023

Preprint

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In recent years, there has been increasing interest in the use of kilohertz frequency alternating current (KHFAC) to block peripheral nerves. However, there is still a lack of direct data and mechanistic studies on the treatment of neuropathic pain by KHFAC. Based on this, we applied a high-frequency bipolar rectangular stimulus pulse to chronic constriction injury of sciatic nerve mice (CCI), and explored the optimal stimulation frequency and current by recording the compound muscle action potential (CMAP). We found that KHFAC could significantly alleviate the mechanical and thermal allodynia in neuropathic pain mice without any effect of movement function following 7 days of high-frequency electrical stimulation of the sciatic nerve. KHFAC inhibited the expression of TRPV1 and NMDAR2B, which could also inhibit the activation of astrocytes and microglia in the spinal cord. The administration of TRPV1 pathway activator could partially reverse the antinociceptive effects of KHFAC, while TRPV1 pathway inhibitor could achieve analgesic effects similar to KHFAC. Therefore, we believe that KHFAC inhibits the activation of spinal dorsal horn glial cells, especially astrocytes and microglia, through nociceptive afferent fibers by inhibiting the activation of TRPV1/NMDAR2B signaling pathway. In summary, KHFAC has a potential to be a novel intervention for the treatment of neuropathic pain.

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“…The NRS scores at 0.5 h, 4 h, 8 h, and 24 h after extubation and the cases of rescue analgesia on POD1 and POD2 in the nalbuphine combined with dexmedetomidine group were the lowest, and the QoR-40 scores were the highest ( P < 0.001), which indicated that the combination of nalbuphine and dexmedetomidine can improve the analgesic effect and the quality of postoperative recovery. The possible reasons for postoperative pain after endoscopic sinus surgery are as follows: surgical trauma causes the release of inflammatory factors and pain mediums and increases the synthesis of prostaglandins, which finally results in pain sensitization [ 16 ]; long-term sleep disorders caused by nasal diseases and the consumption of remifentanil during general anesthesia may lead to postoperative hyperalgesia [ 17 ]; and the effect of postoperative nasal packing on respiration will increase the incidence of headache and discomfort caused by brain hypoxia [ 18 ]. Nalbuphine inhibits the release of substance P from primary afferents by activating the kappa receptor in the spinal cord, thus reducing the transmission of the nerve impulses of pain to the central nervous system [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Preventive Analgesia with Nalbuphine and Dexmedetomidine in Endoscopic Sinus Surgery

Zhang

et al. 2022

Pain Research and Management

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Background. The study was to assess the efficacy and safety of nalbuphine combined with dexmedetomidine for preventive analgesia in endoscopic sinus surgery. Methods. 110 patients with deviation of the nasal septum were randomized into the nalbuphine group (group N), dexmedetomidine combined with nalbuphine group (group DN), and saline group (group C). Fifteen minutes before the induction of anesthesia, patients in group N were injected nalbuphine 0.2 mg/kg intravenously; patients in group DN received intravenous infusion of dexmedetomidine 0.5 μg/kg and injection of nalbuphine 0.2 mg/kg; patients in group C received 0.9% saline. Mean arterial pressure (MAP), heart rate (HR), numerical rating scale (NRS) scores, quality of recovery-40 (QoR-40) scores, the need for remedial analgesia, the consumption of remifentanil and propofol, and the incidence of adverse reactions were recorded. Results. MAP, HR, and NRS scores of the DN group were significantly lower and the QoR-40 scores were higher than those of groups N and C ( P < 0.001 ). The need for remedial analgesia, the consumption of remifentanil and propofol, and the incidence of nausea in the DN group were the lowest among the three groups ( P < 0.001 ). Conclusion. Preventive analgesia with nalbuphine and dexmedetomidine in endoscopic sinus surgery can not only maintain hemodynamic stability but also reduce intraoperative anesthetic dosage, postoperative pain, and improve the quality of postoperative recovery without affecting the revival and extubation time.

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Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats

Abstract: It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

Cited by 12 publications

References 38 publications

Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats

Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats

Kilohertz High-Frequency Alternating Current Ameliorate Hyperalgesia and Inhibit the Glial Activation by Modulating TRPV1 and NMDAR2B Signaling Pathways in Chronic Constriction Injury of Sciatic Nerve Mice

Effect of Preventive Analgesia with Nalbuphine and Dexmedetomidine in Endoscopic Sinus Surgery

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