Identifying molecular mechanisms of acute to chronic pain transition and potential drug targets

Aravagiri, Kannan; Ali, Adam A.; Wang, Hank C; Candido, Kenneth D.; Knežević, Nebojša Nick

doi:10.1080/14728222.2022.2137404

Cited by 3 publications

(3 citation statements)

References 80 publications

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“…Expression levels of genes involved in multiple pain-related mechanisms are regulated at both the transcriptional and translational levels [22]. Emerging evidence have validated the critical role of RNA modi cations in the development and maintenance of pain [23,24].…”

Section: Discussionmentioning

confidence: 99%

N-methyladenosine-modified PIAS1 promotes microglia polarization to M1 by regulating PPARγ SUMOylation in Inflammatory Bowel Disease-associated hyperalgesia

Huang,

Xu,

Hou

et al. 2023

Preprint

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Background and Aims: Large number of nociceptive signals produced by intestinal inflammation are transmitted to the spinal dorsal horn, leading to microglia polarization, which is of great significance in mediating central sensitization. Emerging evidence indicate that m6A modification regulates a dynamic macrophage polarization. However, it remains unsolved to link polarization of microglia regulated by m6a modification to inflammatory bowel disease (IBD) associated hyperalgesia. Methods IBD-induced hyperalgesia was assessed by paw withdrawal mechanical threshold in a murine colitis model induced by dextran sulphate sodium (DSS). MeRIP sequence was performed on the LPS-treated primary microglia. The biological role and mechanism of m6A modified PIAS1 in microglia polarization and central sensitization were determined in vitro and in vivo. Results The level of m6A RNA was significantly increased in the spinal dorsal cord of colitis mice, accompanied by microglia polarization to M1-proinflammatory phenotype, and METTL3 was the main regulator involved in the abundant m6A RNA modification. Moreover, MeRIP sequence identified PIAS1 acts anti-inflammatory function though promoting PPARγ SUMOylation in regulating microglia polarization. Mechanistically, the m6A reader YTHDF2 directly recognized and bound to the m6A site on PIAS1 mRNA and reduced PIAS1 mRNA stability. Overexpression YTHDF2 decreased PIAS1 mRNA level and promoted the polarization to M1-phenotype in vitro. Finally, reduced m6A modification by specific downregulation METTL3 in microglia of the spinal dorsal horn contributes to alleviate IBD-associated hyperalgesia. Conclusions The mRNA stabilization of m6A-modified PIAS1-mediated PPARγ SUMOylation as the underlying mechanism through which METTL3 preserved M1-phenotype microglia contributes to IBD-associated hyperalgesia.

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Section: Discussionmentioning

confidence: 99%

N-methyladenosine-modified PIAS1 promotes microglia polarization to M1 by regulating PPARγ SUMOylation in Inflammatory Bowel Disease-associated hyperalgesia

Huang,

Xu,

Hou

et al. 2023

Preprint

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“…[17][18][19] Oxycodone combined with other analgesic drugs or modalities can regulate pain receptors and conduction pathways at different sites, thereby acting on different targets to interfere with neuronal sensitisation. [20][21][22][23] thus reducing nociceptive sensation and producing additive and synergistic analgesic effects. This is conducive to promoting functional exercise in the early postoperative period as well as in reducing the dosage of opioids used, nausea and vomiting, respiratory depression and other adverse effects.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…Oxycodone combined with other analgesic drugs or modalities can regulate pain receptors and conduction pathways at different sites, thereby acting on different targets to interfere with neuronal sensitisation 20–23. thus reducing nociceptive sensation and producing additive and synergistic analgesic effects.…”

Section: Introductionmentioning

confidence: 99%

Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study

Wang,

Wu,

Liu

et al. 2023

BMJ Open

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IntroductionPostoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and paravertebral nerve block for postoperative analgesia in patients undergoing thoracoscopic lobectomy for lung cancer can achieve a satisfactory analgesic effect and promote early rehabilitation of patients. The objective is to investigate the optimal dose of oxycodone for PCIA combined with paravertebral nerve block, to achieve effective multimodal analgesia management in patients undergoing thoracoscopic lung cancer lobectomy.Methods and analysisThis prospective, double-blind, single-centre, parallel-group, superiority study from 7 April 2023 to 31 December 2024 will include 160 participants scheduled for thoracoscopic lobectomy for lung cancer. Participants will be randomly assigned to four groups in a 1:1:1:1 ratio: OCA group (oxycodone: 0.5 mg/kg), OCB group (oxycodone: 1.0 mg/kg), OCC group (oxycodone: 1.5 mg/kg) and one sufentanil group (sufentanil: 2 µg/kg). Flurbiprofen 50 mg and ondansetron 16 mg are added to each group. All the drugs are diluted with 0.9% saline in a 100 mL volume, with a background infusion rate of 2 mL/hour, a bolus dose of 0.5 mL and a lockout interval of 15 min. The primary outcome is pain scores at rest and dynamic at 24 hours after surgery using a Numeric Rating Scale (NRS). Dynamic NRS scores are defined as NRS when coughing. NRS scores will be assessed at 2, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes include the following variables: (1) NRS score at rest and dynamic at 2, 4, 12 and 48 hours postoperatively; (2) total dose of sufentanil or oxycodone consumption in PCIA; (3) the times of patient-controlled analgesia; (4) Ramsay Sedation Score (RSS) at 2, 4, 12, 24 and 48 hours after the surgery; (5) extubation time; (6) serum C-reactive protein and interleukin six levels; (7) incidence of postoperative nausea and vomiting; (8) incidence of itching; (9) incidence of respiratory depression and (10) gastrointestinal recovery (exhaust time).Ethics and disseminationThe First Affiliated Hospital of Shandong First Medical University’s Ethics Committee granted consent for this study (approval number: YXLL-KY-2022(116)). To enable widespread use of the data gathered, we plan to publish the trial’s findings in an appropriate scientific journal after it is complete.Trial registration numberNCT05742256.

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Electroacupuncture prevents the development or establishment of chronic pain via IL-33/ST2 signaling in hyperalgesic priming model rats

Jin,

Zhou,

Fang

et al. 2024

Neuroscience Letters

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Identifying molecular mechanisms of acute to chronic pain transition and potential drug targets

Cited by 3 publications

References 80 publications

N-methyladenosine-modified PIAS1 promotes microglia polarization to M1 by regulating PPARγ SUMOylation in Inflammatory Bowel Disease-associated hyperalgesia

N-methyladenosine-modified PIAS1 promotes microglia polarization to M1 by regulating PPARγ SUMOylation in Inflammatory Bowel Disease-associated hyperalgesia

Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study

Electroacupuncture prevents the development or establishment of chronic pain via IL-33/ST2 signaling in hyperalgesic priming model rats

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