Current understanding of complex regional pain syndrome

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Abstract

Complex regional pain syndrome (CRPS) is a multifactorial pathology characterized by chronic pain, autonomic disorders, and motor dysfunction. This review discusses the mechanisms of CRPS development, as well as methods of its diagnosis, treatment, and prevention. In addition to drug treatment and physical therapy, issues of interventional methods for the treatment of CRPS are also covered. Along with sympathetic blocks and various ablation techniques under ultrasound and fluoroscopic guidance, a new waveform for spinal cord stimulation and new stimulation targets such as dorsal root ganglia have been proposed.

About the authors

Alexander L. Petrushin

Karpogory central district hospital

Author for correspondence.
Email: petrushin.59@mail.ru
ORCID iD: 0000-0002-3246-7452

MD, Cand. Sci. (Med.)

Russian Federation, 47, Lenina str., Karpogory, Arkhangelsk region, 164600

Eduard E. Antipin

Northern State Medical University

Email: vard67@mail.ru
ORCID iD: 0000-0002-2386-9281
SPIN-code: 8850-2071

MD, Dr. Sci. (Med.), associate professor

Russian Federation, Arkhangelsk

Svetlana V. Bragina

Northern State Medical University

Email: svetabragina69@mail.ru
ORCID iD: 0000-0002-0900-4572
SPIN-code: 5490-9821

MD, Cand. Sci. (Med.), associate professor

Russian Federation, Arkhangelsk

Maxim P. Yakovenko

Northern State Medical University

Email: alter83@mail.ru
ORCID iD: 0000-0002-1267-9781
SPIN-code: 2074-3953

graduate student

Russian Federation, Arkhangelsk

Nadegda A. Bochkareva

Northern State Medical University

Email: noirsept@gmail.com
ORCID iD: 0000-0002-1912-4252

graduate student

Russian Federation, Arkhangelsk

Natalia I. Koroleva

Northern State Medical University

Email: la-reine-soleil@yandex.ru
ORCID iD: 0000-0001-5768-3859

graduate student

Russian Federation, Arkhangelsk

References

  1. Paré A. Of the cure of wounds of the nervous system. In: The collected works of Ambroise Pare. New York: Milford House; 1968;1634–1639.
  2. Doury P, Dirheimer Y, Pattin S. Historical review. In: Algodystrophy: Diagnosis and therapy for frequent disease of the locomotor apparatus. Heidelberg, Berlin: Springer; 1981;2–6.
  3. An DA. Example of symptoms resembling tic douleureux, produced by a wound in the radial nerve. Med Chir Trans.1813;4:48–52.
  4. Sudeck P. Über die akuteentzündlicheKnochenatrophie. Arch KlinChir. 1900;62:147–156.
  5. Shim H, Rose J, Halle S, Shekane P. Complex regional pain syndrome: a narrative review for the practising clinician. Br J Anaesth. 2019;123(2):e424–e433. doi: 10.1016/j.bja.2019.03.030
  6. Elsharydah A, Loo NH, Minhajuddin A, Kandil ES. Complex regional pain syndrome type 1 predictors – Epidemiological perspective from a national database analysis. J Clin Anesth. 2017;39:34–37. doi: 10.1016/j.jclinane.2017.03.027
  7. Murphy KR, Han JL, Yang S, et al. Prevalence of Specific Types of Pain Diagnoses in a Sample of United States Adults. Pain Physician. 2017;20(2):E257–E268.
  8. Taylor SS, Noor N, Urits I, et al. Complex Regional Pain Syndrome: A Comprehensive Review. Pain Ther. 2021;10(2):875–892. doi: 10.1007/s40122-021-00279-4
  9. Ott S, Maihofner C. Signs and Symptoms in 1,043 Patients with Complex Regional Pain Syndrome. J Pain. 2018;19(6):599–611. doi: 10.1016/j.jpain.2018.01.004
  10. Koval K, Haidukewych GJ, Service B, Zirgibel BJ. Controversies in the management of distal radius fractures. J Am Acad Orthop Surg. 2014;22(9):566–575. doi: 10.5435/JAAOS-22-09-566
  11. Crijns TJ, van der Gronde B, Ring D, Leung N. Complex Regional Pain Syndrome After Distal Radius Fracture Is Uncommon and Is Often Associated With Fibromyalgia. Clin Orthop Relat Res. 2018;476(4):744–750. doi: 10.1007/s11999.0000000000000070
  12. Cutts S, Gangoo S, Srinivasan SH, et al. Complex regional pain syndrome: an evolving perspective. Postgrad Med J. 2021;97(1146):250–255. doi: 10.1136/postgradmedj-2020-137808
  13. Misidou C, Papagoras C. Complex Regional Pain Syndrome: An update. Mediterr J Rheumatol. 2019;30(1):16–25. doi: 10.31138/mjr.30.1.16
  14. Baronio M, Sadia H, Paolacci S, et al. Molecular Aspects of Regional Pain Syndrome. Pain Res Manag. 2020;2020:7697214. doi: 10.1155/2020/7697214
  15. Sommer C, Leinders M, Uceyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. 2018;159(3):595–602. doi: 10.1097/j.pain.0000000000001122
  16. Wehmeyer C, Pap T, Buckley CD, Naylor AJ. The role of stromal cells in inflammatory bone loss. Clin Exp Immunol. 2017;189(1):1–11. doi: 10.1111/cei.12979
  17. Littlejohn G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat Rev Rheumatol. 2015;11(11):639–648. doi: 10.1038/nrrheum.2015.100
  18. Yvon A, Faroni A, Reid AJ, Lees VC. Selective Fiber Degeneration in the Peripheral Nerve of a Patient With Severe Complex Regional Pain Syndrome. Front Neurosci. 2018;12:207. doi: 10.3389/fnins.2018.00207
  19. Knudsen LF, Terkelsen AJ, Drummond PD, Birklein F. Complex regional pain syndrome: a focus on the autonomic nervous system. Clin Auton Res. 2019;29(4):457–467. doi: 10.1007/s10286-019-00612-0
  20. Kortekaas MC, Niehof SP, Stolker RJ, Huygen FJ. Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review. Pain Pract. 2016;16(7):905–914. doi: 10.1111/papr.12403
  21. Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns Trauma. 2017;5:2. doi: 10.1186/s41038-016-0066-4
  22. Di Pietro F, McAuley JH, Parkitny L, et al. Primary somatosensory cortex function in complex regional pain syndrome: a systematic review and meta-analysis. J Pain. 2013;14(10):1001–1018. doi: 10.1016/j.jpain.2013.04.001
  23. Tajerian M, Clark JD. New Concepts in Complex Regional Pain Syndrome. Hand Clin. 2016;32(1):41–49. doi: 10.1016/j.hcl.2015.08.003
  24. Cuhadar U, Gentry C, Vastani N, et al. Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors. Pain. 2019;160(12):2855–2865. doi: 10.1097/j.pain.0000000000001662
  25. David Clark J, Tawfik VL, Tajerian M, Kingery WS. Autoinflammatory and autoimmune contributions to complex regional pain syndrome. Mol Pain. 2018;14:1744806918799127. doi: 10.1177/1744806918799127
  26. Dubuis E, Thompson V, Leite MI, et al. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. Pain. 2014;155(11):2408–2417. doi: 10.1016/j.pain.2014.09.022
  27. Bruehl S, Gamazon ER, Van de Ven T, et al. DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury. Pain. 2019;160(10):2328–2337. doi: 10.1097/j.pain.0000000000001624
  28. Park HY, Jang YE, Oh S, Lee PB. Psychological Characteristics in Patients with Chronic Complex Regional Pain Syndrome: Comparisons with Patients with Major Depressive Disorder and Other Types of Chronic Pain. J Pain Res. 2020;13:389–398. doi: 10.2147/JPR.S230394
  29. Speck V, Schlereth T, Birklein F, Maihofner C. Increased prevalence of posttraumatic stress disorder in CRPS. Eur J Pain. 2017;21(3):466–473. doi: 10.1002/ejp.940
  30. Koryachkin VA. Complex regional pain syndrome. Traumatology and Orthopedics of Russia. 2014;20(3):147–156. (In Russ). doi: 10.21823/2311-2905-89
  31. Goebel A, Birklein F, Brunner F, et al. The Valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria. Pain. 2021;162(9):2346–2348. doi: 10.1097/j.pain.0000000000002245
  32. Kalita J, Vajpayee A, Misra UK. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM. 2006;99(2):89–95. doi: 10.1093/qjmed/hcl004
  33. Barbalinardo S, Loer SA, Goebel A, Perez RS. The Treatment of Longstanding Complex Regional Pain Syndrome with Oral Steroids. Pain Med. 2016;17(2):337–343. doi: 10.1093/pm/pnv002
  34. Urits I, Shen AH, Jones MR, et al. Complex Regional Pain Syndrome, Current Concepts and Treatment Options. Curr Pain Headache Rep. 2018;22(2):10. doi: 10.1007/s11916-018-0667-7
  35. Chevreau M, Romand X, Gaudin P, et al. Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo. Joint Bone Spine. 2017;84(4):393–399. doi: 10.1016/j.jbspin.2017.03.009
  36. Trofimovitch D, Baumrucker SJ. Pharmacology Update: Low-Dose Naltrexone as a Possible Nonopioid Modality for Some Chronic, Nonmalignant Pain Syndromes. Am J Hosp Palliat Care. 2019;36(10):907–912. doi: 10.1177/1049909119838974
  37. Siongco PRL, Rosales RL, Moore AP, et al. Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study. J Neural Transm (Vienna). 2020;127(6):935–951. doi: 10.1007/s00702-020-02163-5
  38. Almog S, Aharon-Peretz J, Vulfsons S, et al. The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial. Eur J Pain. 2020;24(8):1505–1516. doi: 10.1002/ejp.1605
  39. Stockings E, Campbell G, Hall WD, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018;159(10):1932–1954. doi: 10.1097/j.pain.0000000000001293
  40. Goebel A, Jacob A, Frank B, et al. Mycophenolate for persistent complex regional pain syndrome, a parallel, open, randomised, proof of concept trial. Scand J Pain. 2018;18(1):29–37. doi: 10.1515/sjpain-2017-0154
  41. Lee SH, Yoo SH, Lee HJ, et al. Anti-Allodynic Effects of Polydeoxyribonucleotide in an Animal Model of Neuropathic Pain and Complex Regional Pain Syndrome. J Korean Med Sci. 2020;35(26):e225. doi: 10.3346/jkms.2020.35.e225
  42. Yang S, Chang MC. Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review. Front Neurol. 2020;11:114. doi: 10.3389/fneur.2020.00114
  43. Alexander GM, Aradillas E, Schwartzman RJ, et al. Retrospective study plasma exchange therapy in patients with complex regional pain syndrome. Pain Physician. 2015;18:383–394.
  44. Kostrub AA, Bur’yanov AA, Polyachenko YV, et al. Nemedikamentoznoe lechenie kompleksnogo regionarnogo bolevogo sindroma 1 tipa (sindrom Zudeka). Meditsinskii zhurnal. 2020;4:145–150.
  45. Nazarova MA, Piradov MA. Zerkal’naya terapiya v neiroreabilitatsii. RMZh. 2014;22(22):1563–1567.
  46. Chau B, Phelan I, Ta P, et al. Immersive Virtual Reality for Pain Relief in Upper Limb Complex Regional Pain Syndrome: A Pilot Study. Innov Clin Neurosci. 2020;17(4–6):47–52. PMC7413329
  47. Moufawad S, Malak O, Mekhail NA. Epidural infusion of opiates and local anesthetics for Complex Regional Pain Syndrome. Pain Pract. 2002;2(2):81–86. doi: 10.1046/j.1533-2500.2002.02010.x
  48. Wie C, Gupta R, Maloney J, et al. Interventional Modalities to Treat Complex Regional Pain Syndrome. Curr Pain Headache Rep. 2021;25(2):10. doi: 10.1007/s11916-020-00904-5
  49. Aleanakian R, Chung BY, Feldmann RE, Jr., Benrath J. Effectiveness, Safety, and Predictive Potential in Ultrasound-Guided Stellate Ganglion Blockades for the Treatment of Sympathetically Maintained Pain. Pain Pract. 2020;20(6):626–638. doi: 10.1111/papr.12892
  50. Narouze S. Ultrasound-guided stellate ganglion block: safety and efficacy. Curr Pain Headache Rep. 2014;18(6):424. doi: 10.1007/s11916-014-0424-5
  51. Datta S, Pai U. Paradiscal extraforaminal technique for lumbar sympathetic block: report of a proposed new technique utilizing a cadaver study. Pain Physician. 2004;7(1):53–57.
  52. Kirvela O, Svedstrom E, Lundbom N. Ultrasonic guidance of lumbar sympathetic and celiac plexus block: a new technique. Reg Anesth. 1992;17(1):43–46.
  53. Konig CW, Schott UG, Pereira PL, et al. MR-guided lumbar sympathicolysis. Eur Radiol. 2002;12(6):1388–1393. doi: 10.1007/s003300101064
  54. Moon JY, Choi JK, Shin JY, et al. A brief report on a technical description of ultrasound-guided lumbar sympathetic block. Korean J Pain. 2017;30(1):66–70. doi: 10.3344/kjp.2017.30.1.66
  55. Cheng J, Salmasi V, You J, et al. Outcomes of Sympathetic Blocks in the Management of Complex Regional Pain Syndrome: A Retrospective Cohort Study. Anesthesiology. 2019;131(4):883–893. doi: 10.1097/ALN.0000000000002899
  56. Isagulyan E, Slavin K, Konovalov N, et al. Spinal cord stimulation in chronic pain: technical advances. Korean J Pain. 2020;33(2):99–107. doi: 10.3344/kjp.2020.33.2.99
  57. Lind AL, Emami Khoonsari P, Sjodin M, et al. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis. Neuromodulation. 2016;19(6):549–562. doi: 10.1111/ner.12473
  58. Chmiela MA, Hendrickson M, Hale J, et al. Direct Peripheral Nerve Stimulation for the Treatment of Complex Regional Pain Syndrome: A 30-Year Review. Neuromodulation. 2021;24(6):971–982. doi: 10.1111/ner.13295
  59. Gill JS, Asgerally A, Simopoulos TT. High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Complex Regional Pain Syndrome: A Case Series of Patients With or Without Previous Spinal Cord Stimulator Implantation. Pain Pract. 2019;19(3):289–294. doi: 10.1111/papr.12739
  60. Deer TR, Levy RM, Kramer J, et al. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain. 2017;158(4):669–681. doi: 10.1097/j.pain.0000000000000814
  61. Zacharias NA, Karri J, Garcia C, et al. Interventional Radiofrequency Treatment for the Sympathetic Nervous System: A Review Article. Pain Ther. 2021;10(1):115–141. doi: 10.1007/s40122-020-00227-8
  62. Svirskii DA, Antipin EE, Bochkareva NA, et al. Cryoanalgesia. Review. Annals of critical care. 2020(4):58–73. doi: 10.21320/1818-474x-2020-4-58-73
  63. Sarridou D, Papadopoulou D, Paraskevopoulos T, Stavropoulou E. Successful treatment of complex regional pain syndrome type 1 of upper limb with cryoneurolysis of the stellate ganglion: A rare case report. Pain Pract. 2022;22(2):285–287. doi: 10.1111/papr.13077
  64. Bodde MI, Dijkstra PU, den Dunnen WF, Geertzen JH. Therapy-resistant complex regional pain syndrome typ–1805. doi: 10.2106/JBJS.J.01329
  65. Ayyaswamy B, Saeed B, Anand A, et al. Quality of life after amputation in patients with advanced complex regional pain syndrome: a systematic review. EFORT Open Rev. 2019;4(9):533–540. doi: 10.1302/2058-5241.4.190008
  66. Aim F, Klouche S, Frison A, et al. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2017;103(3):465–470. doi: 10.1016/j.otsr.2016.12.021
  67. Hernigou J, Labadens A, Ghistelinck B, et al. Vitamin C prevention of complex regional pain syndrome after foot and ankle surgery: a prospective randomized study of three hundred and twenty nine patients. Int Orthop. 2021;45(9):2453–2459. doi: 10.1007/s00264-021-05159-2

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2. Fig. 1. Type 2 CRPS in a 81-year-old patient, 20 years after traumatic brachial plexopathy. It is clinically manifested by flexion contractures of the elbow and wrist joints, deformity of the fingers, trophic skin disorders, pain syndrome and severe allodynia (author’s observation)

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3. Fig. 2. Blockade of the stellate ganglion under fluoroscopic control: a) oblique projection: the needle touches the bone at the C6 level at the junction of the uncinate process and the vertebral body; b) image showing extravascular, extra-intrathecal spread of contrast; c) view after administration of local anesthetic [48]

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4. Fig. 3. Ultrasound-assisted blockade of the stellate ganglion at the C7 level. White circle – blockade zone; 1 – hyperechoic shadow of the transverse process C7; 2 – carotid artery; 3 – jugular vein; 4 – long muscle of the neck; 5 – prevertebral fascia; 6 – esophagus; 7 – trachea; 8 – right lobe of the thyroid gland; white straight lines are the direction of the needle

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5. Fig. 4. Blockade of the lumbar sympathetic ganglion under fluoroscopic control: a – oblique projection, the needle is in contact with the bone above the transverse process at the level of L3; b – lateral view, needle tip at the anterior margin of L3, prevertebral spread of contrast; c – anterior view, the contrast extends to the L3 midline with a lobed “cloudy” pattern [48]

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6. Fig. 5. Ultrasound-assisted blockade of the lumbar sympathetic ganglion: 1 – anterior fascia of the psoas muscle; 2 – psoas muscle; 3 – square muscle of the lower back; 4 – shadow of the body of the IV lumbar vertebra; 5 – articular process of the vertebra; 6 – shadow from the transverse process of the vertebra; 7 – lumbar plexus

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Copyright (c) 2022 Petrushin A.L., Antipin E.E., Bragina S.V., Yakovenko M.P., Bochkareva N.A., Koroleva N.I.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


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