Effectiveness and side effects of immunomodulatory agents for complex regional pain syndrome

Authors

  • Omar Rezk Alshaer Department of Internal Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
  • Abdullah Obaid Binobaid Department of Internal Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
  • Anas Ahmed Nanoh College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Ali Mohammed Asiri College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Khalid Saeed Alravie College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Abdulhadi Mushabbab Alyahya College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Mohammed Ali Alotaif College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Nawaf Ahmed Yahya College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Zuhair Abshan Alshehri College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Anas Mohammed Zarbah College of Medicine, King Khalid University, Abha, Saudi Arabia
  • Mohammed Saeed Alqahtani College of Medicine, King Khalid University, Abha, Saudi Arabia

DOI:

https://doi.org/10.18203/2394-6040.ijcmph20213576

Keywords:

Complex regional pain syndrome, CRPS, Immunomodulation, Anti-Inflammatory, Management, Efficacy

Abstract

The main causes of Complex regional pain syndrome (CRPS) are not fully understood. However, it usually emerges following a surgery or an injury to a limb. Inflammation, musculoskeletal, neuronal, and microvascular abnormalities have been found to contribute to the progression of the disease. Immune cells activation, especially with regards to the early phases of the disease is also indicated in the literature. Accordingly, efforts were directed to manage and enhance such responses, aiming to enhance the outcomes by introducing many immunomodulatory agents for managing patients with CRPS and relieving the associated pain. In this literature review, we have discussed the effectiveness and safety of common immunomodulatory agents for CRPS. We have mainly reviewed the roles of glucocorticoids, TNF-α antagonists, bisphosphonates, and intravenous immunoglobulins administration. Glucocorticoids were among the first reported modalities in the management of the syndrome. However, their use is approached with caution because of their potential systemic side effects. Bisphosphonates and TNF-α antagonists also have validated efficacies and should be administered within the early inflammatory phases to achieve better outcomes. Intravenous immunoglobulins are not adequately validated among the current studies, and evidence shows that they might be useful for a certain subgroup. Therefore, further investigations are required to formulate stronger evidence.

References

Oaklander AL, Horowitz SH. The complex regional pain syndrome. Handb Clin Neurol. 2015;131:481-503.

Xu M. Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and immunotherapies. J Neurol Neurosurg Psychiatry. 2020;91(2):177-88.

Allen G, Galer BS, Schwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain. 1999;80(3):539-44.

Terkelsen AJ, Bach FW, Jensen TS. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia. Anesthesiology. 2008;109(2):297-307.

Birklein F. Complex regional pain syndrome - phenotypic characteristics and potential biomarkers. Nat Rev Neurol. 2018;14(5):272-84.

Gierthmühlen J, Binder A, Baron R. Mechanism-based treatment in complex regional pain syndromes. Nat Rev Neurol. 2014;10(9):518-28.

Parkitny L. Inflammation in complex regional pain syndrome: a systematic review and meta-analysis. Neurology. 2013;80(1):106-17.

Wei T. Acute versus chronic phase mechanisms in a rat model of CRPS. J Neuroinflammation. 2016;13:14.

Lenz M. Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months. Pain. 2013;154(10):2142-9.

Russo MA. Expansion and activation of distinct central memory T lymphocyte subsets in complex regional pain syndrome. J Neuroinflammation. 2019;16(1):63.

Ghozy S. Association of breastfeeding status with risk of autism spectrum disorder: A systematic review, dose-response analysis and meta-analysis. Asian J Psychiatr. 2020;48:101916.

Mahmoud AR. Association between sarcoidosis and cardiovascular comorbidity: A systematic review and meta-analysis. Heart Lung. 2020;49(5):512-7.

Ghozy S. Therapeutic efficacy of hepatitis B virus vaccine in treatment of chronic HBV infections: A systematic review and meta-analysis. Rev Med Virol. 2020;30(3):e2089.

Hashan MR. Association of dengue disease severity and blood group: A systematic review and meta-analysis. Rev Med Virol. 2021;31(1):1-9.

Schaible HG. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci. 2010;1193:60-9.

Huygen FJ. Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002;11(1):47-51.

Bernateck M. The first scintigraphic detection of tumor necrosis factor-alpha in patients with complex regional pain syndrome type 1. Anesth Analg. 2010;110(1):211-5.

Uçeyler N. Differential expression patterns of cytokines in complex regional pain syndrome. Pain, 2007;132(1-2):195-205.

Huygen FJ. Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage. 2004;27(2):101-3.

Schwartzman S. Does route of administration affect the outcome of TNF antagonist therapy? Arthritis research & therapy. 2004;6(2):S19-23.

Goli V. Does thalidomide have an analgesic effect? Current status and future directions. Curr Pain Headache Rep. 2007;11(2):109-14.

Casale RF. Atzeni, and P. Sarzi-Puttini, The therapeutic approach to complex regional pain syndrome: light and shade. Clin Exp Rheumatol. 2015;33(1):126-39.

Schwartzman RJ, Chevlen E, Bengtson K. Thalidomide has activity in treating complex regional pain syndrome. Arch Intern Med. 2003;163(12):1487-8.

Clark DJ. Autoinflammatory and autoimmune contributions to complex regional pain syndrome. Molecular pain. 2018;14.

Strang P. Analgesic effect of bisphosphonates on bone pain in breast cancer patients: a review article. Acta Oncol. 1996;35:50-4.

Chauvineau V. [What is the place of diphosphonates in the treatment of complex regional pain syndrome I?]. Ann Readapt Med Phys. 2005;48(3):150-7.

Dibas M. Incidence and survival rates and trends of skull Base chondrosarcoma: A Population-Based study. Clin Neurol Neurosurg. 2020;198:106153.

Robinson JN, Sandom J, Chapman PT. Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med. 2004;5(3):276-80.

Fujita T. Comparison of the analgesic effects of bisphosphonates: etidronate, alendronate and risedronate by electroalgometry utilizing the fall of skin impedance. J Bone Miner Metab. 2009;27(2):234-9.

Varenna M. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatol. 2013;52(3):534-42.

Yanow JM, Pappagallo, Pillai L. Complex regional pain syndrome (CRPS/RSD) and neuropathic pain: role of intravenous bisphosphonates as analgesics. ScientificWorldJournal. 2008;8:229-36.

Oyen WJG. Reflex sympathetic dystrophy of the hand: an excessive inflammatory response? Pain, 1993;55(2):151-7.

van der Laan L, Goris RJ. Reflex sympathetic dystrophy. An exaggerated regional inflammatory response? Hand Clin. 1997;13(3):373-85.

Masferrer JL. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990;86(4):1375-9.

Kozin F. The reflex sympathetic dystrophy syndrome. I. Clinical and histologic studies: evidence for bilaterality, response to corticosteroids and articular involvement. Am J Med. 1976;60(3):321-31.

Okudan B, Celik C. Determination of inflammation of reflex sympathetic dystrophy at early stages with Tc-99m HIG scintigraphy: preliminary results. Rheumatol Int. 2006;26(5):404-8.

Devor M. Govrin-Lippmann R, Raber P. Corticosteroids suppress ectopic neural discharge originating in experimental neuromas. Pain. 1985;22(2):127-37.

Dellon LE. Andonian, and G.D. Rosson, Lower extremity complex regional pain syndrome: long-term outcome after surgical treatment of peripheral pain generators. J Foot Ankle Surg. 2010;49(1):33-6.

Kozin F. The reflex sympathetic dystrophy syndrome (RSDS). III. Scintigraphic studies, further evidence for the therapeutic efficacy of systemic corticosteroids, and proposed diagnostic criteria. Am J Med. 1981;70(1):23-30.

Christense K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand. 1982;148(8):653-5.

Zyluk A, Puchalski P. Treatment of early complex regional pain syndrome type 1 by a combination of mannitol and dexamethasone. J Hand Surg Eur. 2008;33(2):130-6.

Bianchi C. Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome. Eura Medicophys. 2006;42(2):103-11.

Brown ES. Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy. Ann N Y Acad Sci. 2009;1179:41-55.

Murphy AD, Lloyd-Hughes H, Ahmed J. Complex regional pain syndrome (Type 1) following steroid injection for stenosing tenosynovitis. J Plast Reconstr Aesthet Surg. 2010;63(10):e740-1.

Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain. 1997;73(2):123-39.

Bove GM. Focal nerve inflammation induces neuronal signs consistent with symptoms of early complex regional pain syndromes. Exp Neurol. 2009;219(1):223-7.

Jänig W. The fascination of complex regional pain syndrome. Exp Neurol. 2010;221(1):1-4.

Goebel A. Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med. 2010;152(3):152-8.

Goebel A. Human pooled immunoglobulin in the treatment of chronic pain syndromes. Pain Med. 2002;3(2):119-27.

Goebel A. Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial. Ann Intern Me., 2017;167(7):476-83.

Lewis BJB, Branch DR. Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics. Pharmacol. 2020;105(11-12):618-29.

Aradillas E. Plasma Exchange Therapy in Patients with Complex Regional Pain Syndrome. Pain Physician. 2015;18(4):383-94.

Helyes Z. Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1-induced mechanisms. Proc Natl Acad Sci. 2019;116(26):13067-76.

Tékus V. A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome. Pain. 2014;155(2):299-308.

Downloads

Published

2021-08-27

How to Cite

Alshaer, O. R., Binobaid, A. O., Nanoh, A. A., Asiri, A. M., Alravie, K. S., Alyahya, A. M., Alotaif, M. A., Yahya, N. A., Alshehri, Z. A., Zarbah, A. M., & Alqahtani, M. S. (2021). Effectiveness and side effects of immunomodulatory agents for complex regional pain syndrome. International Journal Of Community Medicine And Public Health, 8(9), 4627–4631. https://doi.org/10.18203/2394-6040.ijcmph20213576

Issue

Section

Review Articles