Exploration of Immunology

Table 1. Summary of pharmacological approaches for cancer pain management.

Class	Examples	Primary use	Key points
Non-opioids	NSAIDs, steroids	Inflammatory/Bone pain	Short-term side effects limit use
Opioids	Morphine, fentanyl, oxycodone	Moderate-severe pain	Mainstay therapy: tolerance, immunosuppression
Co-analgesics	Duloxetine, pregabalin	Neuropathic pain, CIPN	First-line for neuropathic components
NMDA antagonists	Ketamine, esketamine	Refractory, central sensitization	Esketamine: better profile, intranasal
Cannabinoids	THC/CBD formulations	Adjunctive, refractory pain	Limited evidence; immunomodulatory
Immunomodulatory	Anti-NGF, cytokine inhibitors, glial modulators	Bone pain, inflammatory pain	Emerging; target neuroimmune mechanisms

Return to article view

NSAIDs: non-steroidal anti-inflammatory drugs; NMDA: N-methyl-D-aspartate; CBD: cannabidiol; THC: delta-9-tetrahydrocannabinol; NGF: nerve growth factor; CIPN: chemotherapy-induced peripheral neuropathy.

Declarations

Acknowledgments

We extend our sincere gratitude to the Paolo Procacci Foundation for its invaluable support and assistance throughout the publication process. In particular, its assistance was indispensable in researching bibliographic sources and preparing the illustrations.

Author contributions

GV: Conceptualization, Methodology, Visualization, Writing—original draft, Writing—review & editing. DM: Formal analysis, Writing—review & editing. MLGL: Formal analysis, Methodology, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Giustino Varrassi and Matteo Luigi Giuseppe Leoni, who are the Guest Editors of Exploration of Immunology, had no involvement in the decision-making or review process of this manuscript. The other author declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research received no external funding.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18:1437–49. [DOI] [PubMed]

Nathan J N, Shereef M E, Ricardo H A. Cancer pain: a review of epidemiology, clinical quality and value impact. Future Oncol. 2016;13:833–41. [DOI] [PubMed]

Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29:iv166–91. [DOI] [PubMed]

Mantyh PW. Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 2006;7:797–809. [DOI] [PubMed]

Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain. 2012;153:359–65. [DOI] [PubMed]

Russo MM, Sundaramurthi T. An Overview of Cancer Pain: Epidemiology and Pathophysiology. Semin Oncol Nurs. 2019;35:223–8. [DOI] [PubMed]

Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139:267–84. [DOI] [PubMed] [PMC]

Bohren Y, Cachemaille M, Timbolschi ID, Perruchoud C. Understanding the Physiopathology of Pain Pathways for a Practical Approach of Cancer Pain Management. Cardiovasc Intervent Radiol. 2025;48:899–906. [DOI] [PubMed]

McMahon SB, Russa FL, Bennett DLH. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat Rev Neurosci. 2015;16:389–402. [DOI] [PubMed]

10.

Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain. Nat Rev Neurol. 2014;10:694–707. [DOI] [PubMed]

11.

Kouri M, Rekatsina M, Vadalouca A, Viswanath O, Varrassi G. Oral Neuropathy Associated with Commonly used Chemotherapeutic Agents: A Narrative Review. Curr Pain Headache Rep. 2024;28:1209–17. [DOI] [PubMed]

12.

Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10:1361–8. [DOI] [PubMed]

13.

Baethge C, Goldbeck-Wood S, Mertens S. SANRA-a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5. [DOI] [PubMed] [PMC]

14.

Paice JA. Pain in Cancer Survivors: How to Manage. Curr Treat Options Oncol. 2019;20:48. [DOI] [PubMed]

15.

Dupoiron D. Pain in cancer survivors: a challenge for the next decade. Ann Palliat Med. 2023;12:434–6. [DOI] [PubMed]

16.

Mestdagh F, Steyaert A, Lavand’homme P. Cancer Pain Management: A Narrative Review of Current Concepts, Strategies, and Techniques. Curr Oncol. 2023;30:6838–58. [DOI] [PubMed] [PMC]

17.

Treede R, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, et al. A classification of chronic pain for ICD-11. Pain. 2015;156:1003–7. [DOI] [PubMed] [PMC]

18.

Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120:3760–72. [DOI] [PubMed] [PMC]

19.

Falk S, Dickenson AH. Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol. 2014;32:1647–54. [DOI] [PubMed]

20.

Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–84. [DOI] [PubMed]

21.

Murthy SE, Dubin AE, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol. 2017;18:771–83. [DOI] [PubMed]

22.

Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61:157–82. [DOI] [PubMed]

23.

Leoni MLG, Mercieri M, Viswanath O, Cascella M, Rekatsina M, Pasqualucci A, et al. Neuropathic Pain: A Comprehensive Bibliometric Analysis of Research Trends, Contributions, and Future Directions. Curr Pain Headache Rep. 2025;29:73. [DOI] [PubMed] [PMC]

24.

Yoon SY, Oh J. Neuropathic cancer pain: prevalence, pathophysiology, and management. Korean J Intern Med. 2018;33:1058–69. [DOI] [PubMed] [PMC]

25.

Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32. [DOI] [PubMed] [PMC]

26.

Dib-Hajj SD, Yang Y, Black JA, Waxman SG. The Na(V)1.7 sodium channel: from molecule to man. Nat Rev Neurosci. 2012;14:49–62. [DOI] [PubMed]

27.

Zamponi GW, Lewis RJ, Todorovic SM, Arneric SP, Snutch TP. Role of voltage-gated calcium channels in ascending pain pathways. Brain Res Rev. 2009;60:84–9. [DOI] [PubMed] [PMC]

28.

Varrassi G, Leoni MLG, Farì G, Al-Alwany AA, Al-Sharie S, Fornasari D. Neuromodulatory Signaling in Chronic Pain Patients: A Narrative Review. Cells. 2025;14:1320. [DOI] [PubMed] [PMC]

29.

Varrassi G, Paladini A, Tran YV, Pham VP, Alwany AAA, Farì G, et al. Advances in the Pathophysiology and Management of Cancer Pain: A Scoping Review. Cancers (Basel). 2026;18:259. [DOI] [PubMed] [PMC]

30.

Kawasaki Y, Zhang L, Cheng J, Ji R. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008;28:5189–94. [DOI] [PubMed] [PMC]

31.

Liu T, Gao Y, Ji R. Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull. 2012;28:131–44. [DOI] [PubMed] [PMC]

32.

Schweizerhof M, Stösser S, Kurejova M, Njoo C, Gangadharan V, Agarwal N, et al. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nat Med. 2009;15:802–7. [DOI] [PubMed]

33.

Pezet S, McMahon SB. Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci. 2006;29:507–38. [DOI] [PubMed]

34.

Wang WL, Hao YH, Pang X, Tang YL. Cancer pain: molecular mechanisms and management. Mol Biomed. 2025;6:45. [DOI] [PubMed] [PMC]

35.

Varrassi G, Farì G, Tamayo MAN, Gomez MP, Liñeiro AMG, Pereira CL, et al. Mixed pain: clinical practice recommendations. Front Med (Lausanne). 2025;12:1659490. [DOI] [PubMed] [PMC]

36.

Swarm R, Abernethy AP, Anghelescu DL, Benedetti C, Blinderman CD, Boston B, et al. Adult cancer pain. J Natl Compr Canc Netw. 2010;8:1046–86. [DOI] [PubMed] [PMC]

37.

Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152:S2–15. [DOI] [PubMed] [PMC]

38.

Burton AW, Fanciullo GJ, Beasley RD, Fisch MJ. Chronic pain in the cancer survivor: a new frontier. Pain Med. 2007;8:189–98. [DOI] [PubMed]

39.

Cuomo A, Bimonte S, Forte CA, Botti G, Cascella M. Multimodal approaches and tailored therapies for pain management: the trolley analgesic model. J Pain Res. 2019;12:711–4. [DOI] [PubMed] [PMC]

40.

Woolf CJ, Ma Q. Nociceptors--noxious stimulus detectors. Neuron. 2007;55:353–64. [DOI] [PubMed]

41.

Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron. 2007;55:365–76. [DOI] [PubMed]

42.

Bhave G, Gereau RW. Posttranslational mechanisms of peripheral sensitization. J Neurobiol. 2004;61:88–106. [DOI] [PubMed]

43.

Bhave G, Zhu W, Wang H, Brasier D, Oxford GS, Gereau RW. cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron. 2002;35:721–31. [DOI] [PubMed]

44.

Chahine M, Chatelier A, Babich O, Krupp J. Voltage-gated sodium channels in neurological disorders. CNS Neurol Disord Drug Targets. 2008;7:144–58. [DOI] [PubMed]

45.

Jang K, Garraway SM. A review of dorsal root ganglia and primary sensory neuron plasticity mediating inflammatory and chronic neuropathic pain. Neurobiol Pain. 2024;15:100151. [DOI] [PubMed] [PMC]

46.

Sandkühler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev. 2009;89:707–58. [DOI] [PubMed]

47.

Koshland DE, Goldbeter A, Stock JB. Amplification and adaptation in regulatory and sensory systems. Science. 1982;217:220–5. [DOI] [PubMed]

48.

Moore CA, Milano SK, Benovic JL. Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol. 2007;69:451–82. [DOI] [PubMed]

49.

Rosenbaum T, Gordon-Shaag A, Munari M, Gordon SE. Ca²⁺/calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol. 2004;123:53–62. [DOI] [PubMed] [PMC]

50.

Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev. 2013;65:223–54. [DOI] [PubMed] [PMC]

51.

Ji R, Xu Z, Gao Y. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13:533–48. [DOI] [PubMed] [PMC]

52.

Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66:355–474. [DOI] [PubMed]

53.

Ji R, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? Pain. 2013;154:S10–28. [DOI] [PubMed] [PMC]

54.

Cerrone V, Esposito D, Montedoro M, Andretta V, Leoni MLG, Cuomo A, et al. Diagnosis of Chemotherapy-induced Peripheral Neurotoxicity: A Scoping Review. In Vivo. 2025;39:3041–59. [DOI] [PubMed] [PMC]

55.

Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14:502–11. [DOI] [PubMed] [PMC]

56.

Yoon SY, Oh J. Neuropathic cancer pain: prevalence, pathophysiology, and management. Korean J Intern Med. 2018;33:1058–69. [DOI] [PubMed] [PMC]

57.

Devor M. Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res. 2009;196:115–28. [DOI] [PubMed]

58.

Marchesi F, Piemonti L, Mantovani A, Allavena P. Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis. Cytokine Growth Factor Rev. 2010;21:77–82. [DOI] [PubMed]

59.

Selvaggi F, Melchiorre E, Casari I, Cinalli S, Cinalli M, Aceto GM, et al. Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance. Cancers (Basel). 2022;14:5793. [DOI] [PubMed] [PMC]

60.

White FA, Jung H, Miller RJ. Chemokines and the pathophysiology of neuropathic pain. Proc Natl Acad Sci U S A. 2007;104:20151–8. [DOI] [PubMed] [PMC]

61.

Yuan Q, Liu X, Xian YF, Yao M, Zhang X, Huang P, et al. Satellite glia activation in dorsal root ganglion contributes to mechanical allodynia after selective motor fiber injury in adult rats. Biomed Pharmacother. 2020;127:110187. [DOI] [PubMed]

62.

Grosu-Bularda A, Lita F, Hodea F, Bordeanu-Diaconescu E, Cretu A, Dumitru C, et al. Navigating the Complexities of Radiation Injuries: Therapeutic Principles and Reconstructive Strategies. J Pers Med. 2024;14:1100. [DOI] [PubMed] [PMC]

63.

Scott BB, Winograd JM, Redmond RW. Surgical Approaches for Prevention of Neuroma at Time of Peripheral Nerve Injury. Front Surg. 2022;9:819608. [DOI] [PubMed] [PMC]

64.

Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014;14:217–31. [DOI] [PubMed] [PMC]

65.

Inoue K, Tsuda M. Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci. 2018;19:138–52. [DOI] [PubMed]

66.

Trang T, Beggs S, Salter MW. Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain. Neuron Glia Biol. 2011;7:99–108. [DOI] [PubMed] [PMC]

67.

Haist M, Stege H, Grabbe S, Bros M. The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment. Cancers (Basel). 2021;13:210. [DOI] [PubMed] [PMC]

68.

Yang Y, Li S, To KKW, Zhu S, Wang F, Fu L. Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy. J Exp Clin Cancer Res. 2025;44:145. [DOI] [PubMed] [PMC]

69.

Lei Y, Liao F, Tian Y, Wang Y, Xia F, Wang J. Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy. Front Neurosci. 2023;17:1321176. [DOI] [PubMed] [PMC]

70.

Bethea JR, Fischer R. Role of Peripheral Immune Cells for Development and Recovery of Chronic Pain. Front Immunol. 2021;12:641588. [DOI] [PubMed] [PMC]

71.

Zhang C, Li Y, Yu Y, Li Z, Xu X, Talifu Z, et al. Impact of inflammation and Treg cell regulation on neuropathic pain in spinal cord injury: mechanisms and therapeutic prospects. Front Immunol. 2024;15:1334828. [DOI] [PubMed] [PMC]

72.

Spera MC, Cesta MC, Zippoli M, Varrassi G, Allegretti M. Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis. Pain Ther. 2022;11:1113–36. [DOI] [PubMed] [PMC]

73.

Sharma A, Jasrotia S, Kumar A. Effects of Chemotherapy on the Immune System: Implications for Cancer Treatment and Patient Outcomes. Naunyn Schmiedebergs Arch Pharmacol. 2023;397:2551–66. [DOI] [PubMed]

74.

Li C, Qi X, Yan M. Chemotherapy-induced immunogenic cell death in combination with ICIs: a brief review of mechanisms, clinical insights, and therapeutic implications. Front Pharmacol. 2025;16:1572195. [DOI] [PubMed] [PMC]

75.

Li L, Huang Y, Xue R, Li G, Li L, Liang L, et al. T cell-mediated mechanisms of immune-related adverse events induced by immune checkpoint inhibitors. Crit Rev Oncol Hematol. 2025;213:104808. [DOI] [PubMed]

76.

Lashkajani SZ, Azad YS, Nami MT, Darzi A, Shokouhfar M, Faizabadi SN, et al. Neurologic complications of immune checkpoint inhibitors: A comprehensive review. Biomed Pharmacother. 2025;192:118669. [DOI] [PubMed]

77.

Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012;13:e58–68. [DOI] [PubMed]

78.

Varrassi G, Paladini A, Van Tran Y, Van Phong Pham, Al Alwany AA, Farì G, et al. Advances in the Pathophysiology and Management of Cancer Pain: A Scoping Review. Cancers (Basel). 2026;18:259. [DOI] [PubMed] [PMC]

79.

Mercadante S, Sapienza G, Cascio AL, Casuccio A. The Use of Opioids in an Acute Palliative Care Unit to Re-assess Prescriptions. Pain Ther. 2025;14:999–1006. [DOI] [PubMed] [PMC]

80.

Plein LM, Rittner HL. Opioids and the immune system - friend or foe. Br J Pharmacol. 2018;175:2717–25. [DOI] [PubMed] [PMC]

81.

Roy S, Ninkovic J, Banerjee S, Charboneau RG, Das S, Dutta R, et al. Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol. 2011;6:442–65. [DOI] [PubMed] [PMC]

82.

Roy S, Wang J, Kelschenbach J, Koodie L, Martin J. Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol. 2006;1:77–89. [DOI] [PubMed]

83.

Vallejo R, De Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: a review. Am J Ther. 2004;11:354–65. [DOI] [PubMed]

84.

Sessler DI, Pei L, Huang Y, Fleischmann E, Marhofer P, Kurz A, et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet. 2019;394:1807–15. [DOI] [PubMed]

85.

Franchi S, Moschetti G, Amodeo G, Sacerdote P. Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies. Front Immunol. 2019;10:2914. [DOI] [PubMed] [PMC]

86.

Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study. Neuroimmunomodulation. 2004;11:255–60. [DOI] [PubMed]

87.

Missair A, Cata JP, Votta-Velis G, Johnson M, Borgeat A, Tiouririne M, et al. Impact of perioperative pain management on cancer recurrence: an ASRA/ESRA special article. Reg Anesth Pain Med. 2019;44:13–28. [DOI] [PubMed]

88.

Soliman N, Moisset X, Ferraro MC, De Andrade DC, Baron R, Belton J, et al. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. Lancet Neurol. 2025;24:413–28. [DOI] [PubMed]

89.

Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019;129:241–54. [DOI] [PubMed]

90.

Jackson K, Ashby M, Martin P, Pisasale M, Brumley D, Hayes B. “Burst” ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage. 2001;22:834–42. [DOI] [PubMed]

91.

Weinbroum AA, Rudick V, Paret G, Ben-Abraham R. The role of dextromethorphan in pain control. Can J Anaesth. 2000;47:585–96. [DOI] [PubMed]

92.

Sang C, Booher S, Gilron I, Parada S, Max M. Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. Anesthesiology. 2002;96:1053–61. [DOI] [PubMed]

93.

Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther. 2015;97:575–86. [DOI] [PubMed]

94.

Al-Husinat L, Obeidat S, Azzam S, Al-Gwairy Y, Obeidat F, Sharie SA, et al. Role of Cannabis in the Management of Chronic Non-Cancer Pain: A Narrative Review. Clin Pract. 2025;15:16. [DOI] [PubMed] [PMC]

95.

Sic A, George C, Gonzalez DF, Tseriotis V, Knezevic NN. Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges. Neurol Int. 2025;17:141. [DOI] [PubMed] [PMC]

96.

Cabral GA, Griffin-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. 2009;11:e3. [DOI] [PubMed] [PMC]

97.

Faiz MB, Naeem F, Irfan M, Aslam MA, Estevinho LM, Ateşşahin DA, et al. Exploring the therapeutic potential of cannabinoids in cancer by modulating signaling pathways and addressing clinical challenges. Discov Oncol. 2024;15:490. [DOI] [PubMed] [PMC]

98.

Creangă-Murariu I, Rezuș II, Karami R, Rancz A, Zolcsák Á, Engh MA, et al. Indications of Cannabinoids for the Palliation of Cancer-Associated Symptoms: A Systematic Review and Meta-Analysis. Curr Oncol Rep. 2025;27:1080–96. [DOI] [PubMed] [PMC]

99.

Li Z, Li X, Liu J, Sun R, Ye Y, Xiang H, et al. Molecular Mechanisms of Chronic Pain and Therapeutic Interventions. MedComm (2020). 2025;6:e70325. [DOI] [PubMed] [PMC]

100.

Wang W, Hao Y, Pang X, Tang Y. Cancer pain: molecular mechanisms and management. Mol Biomed. 2025;6:45. [DOI] [PubMed] [PMC]

101.

Amit M, Eichwald T, Roger A, Anderson J, Chang A, Vermeer PD, et al. Neuro-immune cross-talk in cancer. Nat Rev Cancer. 2025;25:573–89. [DOI] [PubMed]

102.

Vardeh D, Mannion RJ, Woolf CJ. Toward a Mechanism-Based Approach to Pain Diagnosis. J Pain. 2016;17:T50–69. [DOI] [PubMed] [PMC]

103.

Sopata M, Katz N, Carey W, Smith MD, Keller D, Verburg KM, et al. Efficacy and safety of tanezumab in the treatment of pain from bone metastases. Pain. 2015;156:1703–13. [DOI] [PubMed]

104.

Saldaña R, Carrascosa AJ, Torregrosa AB, Navarrete F, García-Gutiérrez MS, Manzanares J. Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms. Int J Mol Sci. 2025;26:10692. [DOI] [PubMed] [PMC]

105.

Vlachou C, Sarridou D, Grosomanidis V, Voulgaris I, Argiriadou H, Amaniti A. Spinal Cord Stimulation: Mechanisms of Action, Indications, Types, Complications. J Clin Med. 2025;14:8615. [DOI] [PubMed] [PMC]

106.

Leoni MLG, Mercieri M, Varrassi G, Cascella M. Artificial Intelligence in Interventional Pain Management: Opportunities, Challenges, and Future Directions. Transl Med UniSa. 2024;26:134–7. [DOI] [PubMed] [PMC]

107.

Varrassi G, Leoni MLG, Al-Alwany AA, Puttini PS, Farì G. Bioengineering Support in the Assessment and Rehabilitation of Low Back Pain. Bioengineering (Basel). 2025;12:900. [DOI] [PubMed] [PMC]