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Pain in amyotrophic lateral sclerosis: a narrative review

  • Kwak, Soyoung (Department of Physical Medicine and Rehabilitation, Yeungnam University College of Medicine)
  • Received : 2022.05.10
  • Accepted : 2022.05.26
  • Published : 2022.07.31

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition characterized by loss of motor neurons, resulting in motor weakness of the limbs and/or bulbar muscles. Pain is a prevalent but neglected symptom of ALS, and it has a significant negative impact on the quality of life of patients and their caregivers. This review outlines the epidemiology, clinical characteristics, underlying mechanisms, and management strategies of pain in ALS to improve clinical practice and patient outcomes related to pain. Pain is a prevalent symptom among patients with ALS, with a variable reported prevalence. It may occur at any stage of the disease and can involve any part of the body without a specific pattern. Primary pain includes neuropathic pain and pain from spasticity or cramps, while secondary pain is mainly nociceptive, occurring with the progression of muscle weakness and atrophy, prolonged immobility causing degenerative changes in joints and connective tissue, and long-term home mechanical ventilation. Prior to treatment, the exact patterns and causes of pain must first be identified, and the treatment should be tailored to each patient. Treatment options can be classified into pharmacological treatments, including nonsteroidal anti-inflammatory drugs, antiepileptic drugs, drugs for cramps or spasticity, and opioid; and nonpharmacological treatments, including positioning, splints, joint injections, and physical therapy. The development of standardized and specific assessment tools for pain-specific to ALS is required, as are further studies on treatments to reduce pain, diminish suffering, and improve the quality of life of patients with ALS.

Keywords

References

  1. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet 2011;377:942-55. https://doi.org/10.1016/S0140-6736(10)61156-7
  2. Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1994;124(Suppl):96-107. https://doi.org/10.1016/0022-510X(94)90191-0
  3. Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:293-9. https://doi.org/10.1080/146608200300079536
  4. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008;119:497-503. https://doi.org/10.1016/j.clinph.2007.09.143
  5. Turner M, Jenkins L. Defining the syndrome. In: Turner M, Jenkins L, editors. Diagnosing amyotrophic lateral sclerosis: clinical wisdom to facilitate faster diagnosis. Oxford: S. Karger Publishers Limited; 2020. p. 7-24.
  6. Mahoney CJ, Ahmed RM, Huynh W, Tu S, Rohrer JD, Bedlack RS, et al. Pathophysiology and treatment of non-motor dysfunction in amyotrophic lateral sclerosis. CNS Drugs 2021;35:483-505. https://doi.org/10.1007/s40263-021-00820-1
  7. Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011;72:257-68. https://doi.org/10.1016/j.neuron.2011.09.010
  8. Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. Brain 2011;134(Pt 9):2582-94. https://doi.org/10.1093/brain/awr195
  9. Drake ME Jr. Chronic pain syndrome in amyotrophic lateral sclerosis. Arch Neurol 1983;40:453-4. https://doi.org/10.1001/archneur.1983.04050070083025
  10. de Castro-Costa CM, Oria RB, Machado-Filho JA, Franco MT, Diniz DL, Giffoni SD, et al. Amyotrophic lateral sclerosis: clinical analysis of 78 cases from Fortaleza (northeastern Brazil). Arq Neuropsiquiatr 1999;57(3B):761-74. https://doi.org/10.1590/S0004-282X1999000500006
  11. Ganzini L, Johnston WS, Hoffman WF. Correlates of suffering in amyotrophic lateral sclerosis. Neurology 1999;52:1434-40. https://doi.org/10.1212/WNL.52.7.1434
  12. Akerblom Y, Jakobsson Larsson B, Zetterberg L, Asenlof P. The multiple faces of pain in motor neuron disease: a qualitative study to inform pain assessment and pain management. Disabil Rehabil 2020;42:2123-32. https://doi.org/10.1080/09638288.2018.1555615
  13. Chio A, Canosa A, Gallo S, Moglia C, Ilardi A, Cammarosano S, et al. Pain in amyotrophic lateral sclerosis: a population-based controlled study. Eur J Neurol 2012;19:551-5. https://doi.org/10.1111/j.1468-1331.2011.03540.x
  14. Raheja D, Stephens HE, Lehman E, Walsh S, Yang C, Simmons Z. Patient-reported problematic symptoms in an ALS treatment trial. Amyotroph Lateral Scler Frontotemporal Degener 2016;17:198-205. https://doi.org/10.3109/21678421.2015.1131831
  15. Wallace VC, Ellis CM, Burman R, Knights C, Shaw CE, Al-Chalabi A. The evaluation of pain in amyotrophic lateral sclerosis: a case controlled observational study. Amyotroph Lateral Scler Frontotemporal Degener 2014;15:520-7. https://doi.org/10.3109/21678421.2014.951944
  16. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis; Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS): revised report of an EFNS task force. Eur J Neurol 2012;19:360-75. https://doi.org/10.1111/j.1468-1331.2011.03501.x
  17. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009;73:1227-33. https://doi.org/10.1212/WNL.0b013e3181bc01a4
  18. Brettschneider J, Kurent J, Ludolph A. Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev 2013;2013:CD005226.
  19. Stephens HE, Lehman E, Raheja D, Yang C, Walsh S, Mcarthur DB, et al. Pain in amyotrophic lateral sclerosis: patient and physician perspectives and practices. Amyotroph Lateral Scler Frontotemporal Degener 2015;17:21-9.
  20. Truini A, Biasiotta A, Onesti E, Di Stefano G, Ceccanti M, La Cesa S, et al. Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS. J Neurol 2015;262:1014-8. https://doi.org/10.1007/s00415-015-7672-0
  21. Dalla Bella E, Lombardi R, Porretta-Serapiglia C, Ciano C, Gellera C, Pensato V, et al. Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol 2016;23:416-20. https://doi.org/10.1111/ene.12936
  22. Hanisch F, Skudlarek A, Berndt J, Kornhuber ME. Characteristics of pain in amyotrophic lateral sclerosis. Brain Behav 2015;5:e00296.
  23. Pizzimenti A, Aragona M, Onesti E, Inghilleri M. Depression, pain and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study. Funct Neurol 2013;28:115-9.
  24. Jensen MP, Abresch RT, Carter GT, McDonald CM. Chronic pain in persons with neuromuscular disease. Arch Phys Med Rehabil 2005;86:1155-63. https://doi.org/10.1016/j.apmr.2004.11.028
  25. Hurwitz N, Radakovic R, Boyce E, Peryer G. Prevalence of pain in amyotrophic lateral sclerosis: a systematic review and meta-analysis. Amyotroph Lateral Scler Frontotemporal Degener 2021;22:449-58. https://doi.org/10.1080/21678421.2021.1892765
  26. Chio A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol 2017;16:144-57. https://doi.org/10.1016/S1474-4422(16)30358-1
  27. Borasio GD, Voltz R, Miller RG. Palliative care in amyotrophic lateral sclerosis. Neurol Clin 2001;19:829-47. https://doi.org/10.1016/s0733-8619(05)70049-9
  28. Moisset X, Cornut-Chauvinc C, Clavelou P, Pereira B, Dallel R, Guy N. Is there pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis?: a cross-sectional study. Palliat Med 2016;30:486-94. https://doi.org/10.1177/0269216315600332
  29. Lopes LC, Galhardoni R, Silva V, Jorge FM, Yeng LT, Callegaro D, et al. Beyond weakness: Characterization of pain, sensory profile and conditioned pain modulation in patients with motor neuron disease: a controlled study. Eur J Pain 2018;22:72-83. https://doi.org/10.1002/ejp.1091
  30. An R, Li Y, He X, Li C, Li X, Xu Y, et al. The evaluation of pain with nociceptive and neuropathic characteristics from three different perspectives in amyotrophic lateral sclerosis patients: a case controlled observational study in Southwestern China. Neural Plast 2021;2021:5537892.
  31. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain 2014;155:654-62. https://doi.org/10.1016/j.pain.2013.11.013
  32. Taga A, Schito P, Trapasso MC, Zinno L, Pavesi G. Pain at the onset of amyotrophic lateral sclerosis: a cross-sectional study. Clin Neurol Neurosurg 2019;186:105540. https://doi.org/10.1016/j.clineuro.2019.105540
  33. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012;2012:CD001447.
  34. Moon ES, Karadimas SK, Yu WR, Austin JW, Fehlings MG. Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy. Neurobiol Dis 2014;62:394-406. https://doi.org/10.1016/j.nbd.2013.10.020
  35. Poupon L, Lamoine S, Pereira V, Barriere DA, Lolignier S, Giraudet F, et al. Targeting the TREK-1 potassium channel via riluzole to eliminate the neuropathic and depressive-like effects of oxaliplatin. Neuropharmacology 2018;140:43-61. https://doi.org/10.1016/j.neuropharm.2018.07.026
  36. Palese F, Sartori A, Logroscino G, Pisa FE. Predictors of diagnostic delay in amyotrophic lateral sclerosis: a cohort study based on administrative and electronic medical records data. Amyotroph Lateral Scler Frontotemporal Degener 2019;20:176-85. https://doi.org/10.1080/21678421.2018.1550517
  37. Galvin M, Ryan P, Maguire S, Heverin M, Madden C, Vajda A, et al. The path to specialist multidisciplinary care in amyotrophic lateral sclerosis: a population- based study of consultations, interventions and costs. PLoS One 2017;12:e0179796. https://doi.org/10.1371/journal.pone.0179796
  38. Paganoni S, Macklin EA, Lee A, Murphy A, Chang J, Zipf A, et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener 2014;15:453-6. https://doi.org/10.3109/21678421.2014.903974
  39. Belsh JM, Schiffman PL. Misdiagnosis in patients with amyotrophic lateral sclerosis. Arch Intern Med 1990;150:2301-5. https://doi.org/10.1001/archinte.1990.00390220055011
  40. Chio A. ISIS Survey: an international study on the diagnostic process and its implications in amyotrophic lateral sclerosis. J Neurol 1999;246(Suppl 3):III1-5.
  41. Cellura E, Spataro R, Taiello AC, La Bella V. Factors affecting the diagnostic delay in amyotrophic lateral sclerosis. Clin Neurol Neurosurg 2012;114:550-4. https://doi.org/10.1016/j.clineuro.2011.11.026
  42. Househam E, Swash M. Diagnostic delay in amyotrophic lateral sclerosis: what scope for improvement? J Neurol Sci 2000;180:76-81. https://doi.org/10.1016/S0022-510X(00)00418-4
  43. Miller TM, Layzer RB. Muscle cramps. Muscle Nerve 2005;32:431-42. https://doi.org/10.1002/mus.20341
  44. Swash M, Czesnik D, de Carvalho M. Muscular cramp: causes and management. Eur J Neurol 2019;26:214-21. https://doi.org/10.1111/ene.13799
  45. Caress JB, Ciarlone SL, Sullivan EA, Griffin LP, Cartwright MS. Natural history of muscle cramps in amyotrophic lateral sclerosis. Muscle Nerve 2016;53:513-7. https://doi.org/10.1002/mus.24892
  46. Mayer NH. Clinicophysiologic concepts of spasticity and motor dysfunction in adults with an upper motoneuron lesion. Muscle Nerve Suppl 1997;6:S1-13.
  47. Verschueren A, Grapperon AM, Delmont E, Attarian S. Prevalence of spasticity and spasticity-related pain among patients with amyotrophic lateral sclerosis. Rev Neurol (Paris) 2021;177:694-8. https://doi.org/10.1016/j.neurol.2020.08.009
  48. Smart KM, Blake C, Staines A, Doody C. Clinical indicators of 'nociceptive', 'peripheral neuropathic' and 'central' mechanisms of musculoskeletal pain: a Delphi survey of expert clinicians. Man Ther 2010;15:80-7. https://doi.org/10.1016/j.math.2009.07.005
  49. Borasio GD, Shaw PJ, Hardiman O, Ludolph AC, Sales Luis ML, Silani V, et al. Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey. Amyotroph Lateral Scler Other Motor Neuron Disord 2001;2:159-64. https://doi.org/10.1080/146608201753275517
  50. Ho DT, Ruthazer R, Russell JA. Shoulder pain in amyotrophic lateral sclerosis. J Clin Neuromuscul Dis 2011;13:53-5. https://doi.org/10.1097/CND.0b013e31821c5623
  51. Hayashi T, Narita Y, Okugawa N, Hamaguchi E, Shibahara M, Kuzuhara S. Pressure ulcers in ALS patients on admission at a university hospital in Japan. Amyotroph Lateral Scler 2007;8:310-3. https://doi.org/10.1080/17482960701538825
  52. Hirano YM, Yamazaki Y, Shimizu J, Togari T, Bryce TJ. Ventilator dependence and expressions of need: a study of patients with amyotrophic lateral sclerosis in Japan. Soc Sci Med 2006;62:1403-13. https://doi.org/10.1016/j.socscimed.2005.08.015
  53. Rivera I, Ajroud-Driss S, Casey P, Heller S, Allen J, Siddique T, et al. Prevalence and characteristics of pain in early and late stages of ALS. Amyotroph Lateral Scler Frontotemporal Degener 2013;14:369-72. https://doi.org/10.3109/21678421.2012.751614
  54. Wigand B, Schlichte I, Schreiber S, Heitmann J, Meyer T, Dengler R, et al. Characteristics of pain and the burden it causes in patients with amyotrophic lateral sclerosis: a longitudinal study. Amyotroph Lateral Scler Frontotemporal Degener 2022;23:284-91. https://doi.org/10.1080/21678421.2021.1962354
  55. Isaacs JD, Dean AF, Shaw CE, Al-Chalabi A, Mills KR, Leigh PN. Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder? J Neurol Neurosurg Psychiatry 2007;78:750-3.
  56. D'Ovidio F, d'Errico A, Farina E, Calvo A, Costa G, Chio A. Amyotrophic lateral sclerosis incidence and previous prescriptions of drugs for the nervous system. Neuroepidemiology 2016;47:59-66. https://doi.org/10.1159/000448618
  57. Adelman EE, Albert SM, Rabkin JG, Del Bene ML, Tider T, O'Sullivan I. Disparities in perceptions of distress and burden in ALS patients and family caregivers. Neurology 2004;62:1766-70. https://doi.org/10.1212/01.WNL.0000125180.04000.A4
  58. Pagnini F, Lunetta C, Banfi P, Rossi G, Fossati F, Marconi A, et al. Pain in amyotrophic lateral sclerosis: a psychological perspective. Neurol Sci 2012;33:1193-6. https://doi.org/10.1007/s10072-011-0888-6
  59. National Institute for Health and Care Excellence (NICE). NICE guideline. Motor neuron disease: assessment and management [Internet]. London: NICE; 2016 [cited 2022 May 8]. https://www.nice.org.uk/guidance/ng42.
  60. Ng L, Khan F, Young CA, Galea M. Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2017;1:CD011776.
  61. Cruccu G, Truini A. A review of neuropathic pain: from guidelines to clinical practice. Pain Ther 2017;6(Suppl 1):35-42. https://doi.org/10.1007/s40122-017-0087-0
  62. Oliver D. Opioid medication in the palliative care of motor neurone disease. Palliat Med 1998;12:113-5. https://doi.org/10.1191/026921698677326556
  63. Baldinger R, Katzberg HD, Weber M. Treatment for cramps in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst R 2012;(4):CD004157.
  64. Bello-Haas VD. Physical therapy for individuals with amyotrophic lateral sclerosis: current insights. Degener Neurol Neuromuscul Dis 2018;8:45-54.
  65. Majmudar S, Wu J, Paganoni S. Rehabilitation in amyotrophic lateral sclerosis: why it matters. Muscle Nerve 2014;50:4-13. https://doi.org/10.1002/mus.24202
  66. McClelland S 3rd, Bethoux FA, Boulis NM, Sutliff MH, Stough DK, Schwetz KM, et al. Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle Nerve 2008;37:396-8. https://doi.org/10.1002/mus.20900
  67. Yang J, Bauer BA, Wahner-Roedler DL, Chon TY, Xiao L. The modified WHO analgesic ladder: is it appropriate for chronic non-cancer pain? J Pain Res 2020;13:411-7. https://doi.org/10.2147/jpr.s244173
  68. Anekar AA, Cascella M. WHO analgesic ladder. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 May 10]. https://www.ncbi.nlm.nih.gov/books/NBK554435/.