Trends in Immunotherapy

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Clinical Research on the Regulation of Perioperative Inflammatory Response by Regional Anesthesia via the Neuro-immune Axis

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https://doi.org/10.54963/ti.v9i4.1683
Wang, D. (2025). Clinical Research on the Regulation of Perioperative Inflammatory Response by Regional Anesthesia via the Neuro-immune Axis. Trends in Immunotherapy, 9(4), 302–331. https://doi.org/10.54963/ti.v9i4.1683
Volume 9 Issue 4 (2025)
Copyright (c) 2025 Dawei Wang
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Authors

  • Dawei Wang

    Department of Anesthesiology, Beijing Jiahe Women & Children’s Hospital, Beijing 100068, China

Received: 9 October 2025; Revised: 20 November 2025; Accepted: 2 December 2025; Published: 18 December 2025

This study enrolled 120 patients undergoing elective abdominal or orthopedic surgery (aged 18–75 years, ASA classification I-III) and employed a prospective randomized controlled design to evaluate the effects of regional anesthesia (RA group, n = 60) versus general anesthesia (GA group, n = 60) on perioperative neuro-immune regulation. Through systematic assessment of perioperative cytokine profiles, immune cell subsets, autonomic nervous function, and clinical outcome indicators, we investigated the mechanisms underlying the role of regional anesthesia in inflammation control. The results demonstrated that at 24 h postoperatively, serum IL-6 levels in the RA group were significantly lower than those in the GA group (156.8 ± 35.7 vs 215.3 ± 41.2 pg/ml, p < 0.001), with the IL-6/IL-10 ratio reduced by 46.2% (1.89 ± 0.35 vs 3.51 ± 0.62, p < 0.001), indicating optimized pro-inflammatory/anti-inflammatory balance. Regarding immune cell function, the RA group showed a 56.9% decrease in M1/M2 ratio (0.59 ± 0.15 vs 1.37 ± 0.28, p < 0.001), maintained higher NK cell cytotoxic activity (58.3 ± 9.5% vs 38.7 ± 7.8%, p < 0.001), and exhibited a 213% increase in Treg/Th17 ratio (1.44 ± 0.28 vs 0.46 ± 0.12, p < 0.001). Autonomic nervous function assessment revealed that the RA group had 103.8% higher HRV-HF power (785.3 ± 142.6 vs 385.4 ± 98.7 ms², p < 0.001), 55.1% lower LF/HF ratio (1.28 ± 0.35 vs 2.85 ± 0.62, p < 0.001), and 77.3% elevated plasma acetylcholine levels (32.8 ± 7.5 vs 18.5 ± 5.2 pmol/ml, p < 0.001). Correlation analysis indicated that HRV-HF was positively correlated with IL-10 (r = 0.625, p < 0.001), and the LF/HF ratio was positively correlated with IL-6 (r = 0.512, p < 0.01), suggesting an association between autonomic nervous function and immune status. In terms of clinical outcomes, the RA group demonstrated lower postoperative pain scores, reduced incidence of cognitive dysfunction, and shortened hospital stay. This study suggests that regional anesthesia may improve perioperative inflammatory response by optimizing autonomic nervous balance, regulating cytokine networks, and modulating immune cell function; however, the precise mechanistic pathways require further investigation and validation.

Keywords:

Regional Anesthesia Neuroimmune Modulation Perioperative Inflammation Cytokines Autonomic Nervous System Immune Cells Cholinergic Anti-Inflammatory Pathway

References

  1. Zhang, T.T.; Liu, J.J.; Ding, P.P.; et al. Effects of stellate ganglion block combined with general anesthesia on postoperative cognitive function and inflammatory factors in elderly patients undergoing hepatectomy for liver cancer. J. Transl. Med. 2025, 14, 152–156. (in Chinese)
  2. Gargano, F.; Fiore, M.; McCaffery, E.; et al. Regional anesthesia as an alternative to general anesthesia for managing polytrauma surgically. Anaesthesiol. Intensive Ther. 2025, 57, 215–218.
  3. Fülesdi, B.; Luterán, P.; Boktor, M.; et al. Time course of a single, 0.6 mg/kg dose of rocuronium neuromuscular block during sevoflurane or propofol anesthesia in infants—a prospective, randomized trial. J. Clin. Med. 2025, 14, 6459.
  4. Yan, L.H.; Zhang, Y.Y.; Yan, J.M.; et al. Study on the effect of glutathione in improving cognitive function, inflammatory oxidative stress and neurotrophic factors in patients under general anesthesia. Chin. J. Health Care Med. 2025, 27, 592–596. (in Chinese)
  5. Zhao, Z.; Xu, F.; Wan, H. Innovative limitations and prospective recommendations on "Assessing the efficiency of non-operating room anesthesia (NORA) using performance boundaries". J. Med. Syst. 2025, 49, 114.
  6. Yan, H.; Peng, M.J.; Xia, R.; et al. Research progress on the role of neuroinflammation in postoperative delirium. Stroke Nerv. Dis. 2025, 32, 438–442.
  7. Fan, W.C.; Li, M.X.; Hou, Q.H. Effects of subarachnoid block combined with nerve block anesthesia on early postoperative cognitive function, emotional response and inflammatory indicators in patients undergoing cesarean section. Chin. J. Fam. Plan. 2025, 33, 1735–1741. (in Chinese)
  8. Zhu, H.; Dong, Z.Q.; Huang, M.H.; et al. Effects of general anesthesia combined with nerve block under anesthesia depth index monitoring on hemodynamics and inflammatory response in elderly patients with acute abdomen. Qingdao Med. J. 2025, 57, 168–171. (in Chinese)
  9. Tang, X.; Li, P. Anesthetic management of tracheal tumor resection with preservation of spontaneous breathing under laryngeal mask airway general anesthesia combined with epidural anesthesia. BMC Anesthesiol. 2025, 25, 451.
  10. Orr, M.N.; Villaluz, E.J.; So, B.; et al. Management of high spinal anesthesia for cesarean section in the semi-Fowler's position. Cureus 2025, 17, e93296.
  11. Chen, X.Y.; Lu, X.Q.; Zhu, K.R.; et al. Effects of methylene blue combined with ropivacaine saphenous nerve block on postoperative inflammatory response and nocturnal sleep quality in patients undergoing total knee arthroplasty. J. Clin. Exp. Med. 2025, 24, 1222–1226. (in Chinese)
  12. Liu, X.T. Effects of celecoxib premedication combined with lumbar plexus nerve block and general anesthesia on postoperative pain, inflammatory factors and joint function recovery in patients undergoing hip replacement. Harbin Med. J. 2025, 45, 40–43. (in Chinese)
  13. Zhang, S.F.; Li, M.; Liu, J.J. Research progress on neuroinflammation as a potential mechanism and therapeutic strategy for postoperative cognitive dysfunction. J. Transl. Med. 2025, 14, 262–268. Available online: https://d.wanfangdata.com.cn/periodical/ChtQZXJpb2RpY2FsQ0hJMjAyNTA2MTcxNjU3NTMSD3poeXh6ejIwMjUwMjA1MRoIcDI1Ym9jaWs%3D (in Chinese)
  14. Wei, J.P.; Chen, W.X.; Tong, Q.L. Evaluation of cervical-brachial plexus nerve block assisted with dexmedetomidine anesthesia in shoulder joint surgery. North. Pharm. 2024, 21, 82–84. Available online: https://d.wanfangdata.com.cn/periodical/bfyx202409027 (in Chinese)
  15. Vinay, B.; Manohara, N.; Jain, A. Anesthesia considerations in older adults undergoing emergency mechanical thrombectomy for acute ischaemic stroke. Drugs Aging 2025, 42, 1–33. DOI: https://doi.org/10.1007/s40266-025-01246-w
  16. Dincklage, V.F.; Helfrich, J.; Koch, S.; et al. Introducing the Safe Brain Initiative's EEG boot camp for anaesthesia for standardised training on how to use the electroencephalogram for perioperative care. BMC Anesthesiol. 2025, 25, 449. DOI: https://doi.org/10.1186/s12871-025-03276-8
  17. Yoshida, K.; Akama, Y.; Inoue, S. Learning from the aircraft cockpit: optimizing anesthesia workspace layout within the primary field of view. JA Clin. Rep. 2025, 11, 48.
  18. You, Q.; Meng, Y.; Liu, X.; et al. Clinical efficacy of COMBO endoscopy of oropharyngeal airways in elderly patients undergoing painless gastroenteroscopy under anaesthesia: a randomized controlled trial protocol. BMC Anesthesiol. 2025, 25, 453.
  19. Takuli, A.; Bhatnagar, A.; Rikhari, P. Effectiveness of topical ajwain oil in reducing pain during local anaesthesia administration in paediatric dental patients: A randomized controlled trial. J. Oral Biol. Craniofac. Res. 2025, 15, 1454–1459.
  20. Zhang, Y.L.; Wei, J.J.; Li, N. Remifentanil suppresses cerebral ischemia-reperfusion induced neuroinflammation and HMGB1-RAGE signaling activity in rats. Chin. J. Histochem. Cytochem. 2024, 33, 361–369. (in Chinese)
  21. Evangelista, T.; Pugno, C.; Finazzi, S.; et al. Regional anesthesia for hip surgery: A review of current approaches and their application to clinical practice. Saudi J. Anaesth. 2025, 19, 164–173. DOI: https://doi.org/10.4103/sja.sja_68_25
  22. Taufik, S.; Kulsum, K. Case report: Administration of anticoagulant therapy after neuro-anesthesia procedure for hemorrhagic stroke patients with COVID-19 complications and its ethical and medicolegal consideration. F1000Research 2021, 10, 1303.
  23. Bailey, L.; Shehata, N.N.; France, D.B.; et al. Obstetric neuraxial anesthesia at low platelet counts in the context of immune thrombocytopenia: A systematic review and meta-analysis. Obstet. Anesth. Dig. 2020, 40, 165–166.
  24. Nathanson, M.H.; Andrzejowski, J.; Dinsmore, J.; et al. Guidelines for safe transfer of the brain-injured patient: trauma and stroke, 2019: Guidelines from the Association of Anaesthetists and the Neuro Anaesthesia and Critical Care Society. Anaesthesia 2020, 75, 234–246. DOI: https://doi.org/10.1111/anae.14866
  25. Wolters Kluwer Health, Inc. Abstracts from the Neuro Anaesthesia and Critical Care Society Annual Scientific Meeting: Glasgow, May 9 to 10, 2019. J. Neurosurg. Anesthesiol. 2020, 32, e1–e9. Available online: https://www.ovid.com/jnls/jnsa/abstract/10.1097/ana.0000000000000649~abstracts-from-the-neuro-anaesthesia-and-critical-care?redirectionsource=fulltextview
  26. Silva, A.V.; Gamas, D.L.; Macedo, P.J.; et al. Hemodynamic Predictors And Changes During Carotid Endarterectomy Under Regional Anesthesia. Rev. Port. Cir. Cardiotorac. Vasc. 2025, 32, 13–23. DOI: https://doi.org/10.48729/pjctvs.502
  27. Setiadi, I.; Alifahna, R.M.; Halimi, A.R.; et al. Role of regional anesthesia in minimizing opioid use and enhancing patient recovery: a case series. J. Med. Case Rep. 2025, 19, 177. DOI: https://doi.org/10.1186/s13256-025-05177-3
  28. Cicirelli, V.; Debidda, P.; Maggio, N.; et al. Use of spinal anaesthesia with anaesthetic block of intercostal nerves compared to a continuous infusion of sufentanyl to improve analgesia in cats undergoing unilateral mastectomy. Animals 2021, 11, 887. DOI: https://doi.org/10.3390/ani11030887
  29. Eun, J.K.; Hoon, S.K.; Woo, R.H.; et al. Postdural puncture headache related to procedure: Incidence and risk factors after neuraxial anesthesia and spinal procedures. Pain Med. 2021, 22, 1420–1425.
  30. Yap, E.N.; Behrends, M. Editorial commentary: Neuraxial anesthesia improves pain after hip arthroscopy but risks ambulatory discharge delay. Arthrosc. J. Arthrosc. Relat. Surg. 2021, 37, 147–148. DOI: https://doi.org/10.1016/j.arthro.2020.10.028
  31. Diwan, S.; Panchawagh, S.; Sancheti, K.P.; et al. Effect of Regional Anesthesia Techniques on Hemodynamic Variables Measured With FloTrac/Vigileo™ System: A Prospective Cohort Study. Cureus 2025, 17, e92589. DOI: https://doi.org/10.7759/cureus.92589
  32. Galli, P.; Labandeyra, H.; Irizaga, G.; et al. Nine key steps in regional anaesthesia: infographic for clinical adoption. Rev. Esp. Anestesiol. Reanim. (Engl. Ed.) 2025, 72, 501900. DOI: https://doi.org/10.1016/j.redare.2025.501900
  33. Hammarqvist, F.; Schumacher, M. Invited commentary: Neuraxial anaesthesia for appendectomy: Another tool in the toolbox. World J. Surg. 2021, 45, 3302–3303. DOI: https://doi.org/10.1007/s00268-021-06002-w
  34. Jowett, N.; Pineda, R. Corneal and facial sensory neurotization in trigeminal anesthesia. Facial Plast. Surg. Clin. N. Am. 2021, 29, 459–470. DOI: https://doi.org/10.1016/j.fsc.2021.03.011
  35. Hagen, J.; Geburek, F.; Kathrinaki, V.; et al. Effect of perineural anesthesia on the centre of pressure (COP) path during stance phase at trot in sound horses. J. Equine Vet. Sci. 2021, 101, 103429. DOI: https://doi.org/10.1016/j.jevs.2021.103429
  36. Dost, B. Fascial plane blocks in the era of modern regional anesthesia: shaping the future of pain management. J. Anesth. Analg. Crit. Care 2025, 5, 49. DOI: https://doi.org/10.1186/s44158-025-00269-4
  37. Alsubhi, H,A.; Alanazi, S.; Atham, T.S.; et al. Comparing outcomes of local and regional anesthesia in vitreoretinal surgery — A systematic review and network meta-analysis. Surv. Ophthalmol. 2025, 70, 1170–1180. DOI: https://doi.org/10.1016/j.survophthal.2025.05.003
  38. Wolters Kluwer Health, Inc. Abstracts from the Neuro Anaesthesia and Critical Care Society, UK Annual Scientific Meeting: Nottingham May 11–12, 2023. J. Neurosurg. Anesthesiol. 2024, 36, e1–e9. Available online: https://www.ovid.com/jnls/jnsa/abstract/10.1097/ana.0000000000000943~abstracts-from-the-neuro-anaesthesia-and-critical-care?redirectionsource=fulltextview
  39. Bold, J.; Szemet, M.; Goździewska-Harłajczuk, K.; et al. Topography of cranial foramina and anaesthesia techniques of cranial nerves in selected species of primates (Cebidae, Cercopithecidae, Lemuridae) — part I — osteology. BMC Vet. Res. 2023, 19, 122. DOI: https://doi.org/10.1186/s12917-023-03680-7
  40. Wolters Kluwer Health, Inc. Abstracts from the Neuro Anaesthesia and Critical Care Society, UK Annual Scientific Meeting: Birmingham May 9 to 10, 2022. J. Neurosurg. Anesthesiol. 2023, 35, e1–e5. Available online: https://www.ovid.com/jnls/jnsa/abstract/10.1097/ana.0000000000000890~abstracts-from-the-neuro-anaesthesia-and-critical-care?redirectionsource=fulltextview
  41. Gerritsen, J.K.W.; Rizopoulos, D.; Schouten, J.W.; et al. Impact of dedicated neuro-anesthesia management on clinical outcomes in glioblastoma patients: A single-institution cohort study. PLoS One 2022, 17, e0278864. DOI: https://doi.org/10.1371/journal.pone.0278864
  42. Moores, C.; Maguire D.; Fruci, P.V.; et al. Regional anesthesia use as a bridge to the provision of medical assistance in dying. Can. J. Anesth./J. Can. Anesth. 2025, 72, 1021–1022. DOI: https://doi.org/10.1007/s12630-025-02956-w
  43. Moia, C.L.A.; Branco, É.; Mesquita, E.Y.E.; et al. Topography and morphometry of the infraorbital and mandibular foramen of the common sloth (Bradypus variegatus) for use in the application of perineural anaesthesia. Anat. Histol. Embryol. 2024, 53, e13028.
  44. Stendall, C.; Bowes, L.; Carver, E. Anaesthesia for paediatric neurosurgery. Part 2: common neurosurgical procedures in children. BJA Educ. 2024, 24, 39–45.
  45. Du, K.X.; Gao, C.J.; Li, X.Q.; et al. Effect of general anesthesia combined with paravertebral nerve block in thoracoscopic lobectomy and its effects on postoperative cognitive function and inflammatory response. Prog. Mod. Biomed. 2022, 22, 4361–4365.
  46. Chen, W.; Fang, Y.; Li, G.; et al. Application effect of ultrasound-guided thoracic paravertebral nerve block combined with general anesthesia in thoracoscopic surgery for tuberculous empyema patients. Guangxi Med. J. 2022, 44, 19–22.
  47. Shafiq, F.; Sheikh, H.; Ahsan, K.; et al. Neuro-anaesthesia training in Pakistan: Evaluating the need for a dedicated fellowship program. Pak. J. Med. Sci. 2025, 41, 1311–1317.
  48. Qian, D.; Olumuyide, E.; Keswani, A.; et al. The impact of race/ethnicity on disparities in utilization and outcomes of neuraxial anesthesia for hip and femoral shaft fractures. J. Clin. Med. 2024, 13, 3999.