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Impaired pain processing and its association with attention disturbance in patients with amyotrophic lateral sclerosis

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Abstract

Background

Cognitive dysfunction characterized by executive dysfunction and persistent attention function has been reported in patients with amyotrophic lateral sclerosis (ALS); however, it is unclear if this contributes to the pain processing deficits associated with the disease.

Objective

We clarified the relationship between pain processing and both cognitive function and sensory symptoms in patients with ALS.

Methods

We enrolled 23 patients with ALS and 14 healthy control subjects. We examined pain-related somatosensory evoked potentials (SEPs) using an intra-epidermal needle electrode. We evaluated cognitive function and the clinical characteristics of sensation and analyzed their relationships with pain-related SEPs.

Results

Pain-related SEP amplitudes were significantly lower, while the rate of amplitude attenuation due to habituation or change in attention was significantly greater in patients with ALS than in control subjects. There were no significant differences in pain-related SEP parameters between patients with or without sensory symptoms. Instead, pain-related SEP amplitude and its rate of attenuation were correlated with cognitive dysfunction, particularly with attention domains.

Conclusions

Our results suggest that attention deficit, but not sensory nerve involvement, is a major cause of the alterations in pain-related SEP in patients with ALS.

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References

  1. Couratier P, Corcia P, Lautrette G, Nicol M, Marin B (2017) ALS and frontotemporal dementia belong to a common disease spectrum. Rev Neurol (Paris) 173(5):273–279. https://doi.org/10.1016/j.neurol.2017.04.001

    Article  CAS  Google Scholar 

  2. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133. https://doi.org/10.1126/science.1134108

    Article  CAS  Google Scholar 

  3. Strong MJ, Abrahams S, Goldstein LH, Woolley S, McLaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, HortobáGyi T, Rosenfeld J, Silani V, Ince PG, Turner MR (2017) Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener 18(3–4):153–174. https://doi.org/10.1080/21678421.2016.1267768

    Article  PubMed  PubMed Central  Google Scholar 

  4. Volpato C, Prats Sedano MA, Silvoni S, Segato N, Cavinato M, Merico A, Piccione F, Palmieri A, Birbaumer N (2016) Selective attention impairment in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 17(3–4):236–244. https://doi.org/10.3109/21678421.2016.1143514

    Article  PubMed  Google Scholar 

  5. McMackin R, Dukic S, Broderick M, Iyer PM, Pinto-Grau M, Mohr K, Chipika R, Coffey A, Buxo T, Schuster C, Gavin B, Heverin M, Bede P, Pender N, Lalor EC, Muthuraman M, Hardiman O, Nasseroleslami B (2019) Dysfunction of attention switching networks in amyotrophic lateral sclerosis. Neuroimage Clin 22:101707. https://doi.org/10.1016/j.nicl.2019.101707

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jamal GA, Weir AI, Hansen S, Ballantyne JP (1985) Sensory involvement in motor neuron disease: further evidence from automated thermal threshold determination. J Neurol Neurosurg Psychiatry 48(9):906–910. https://doi.org/10.1136/jnnp.48.9.906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sassone J, Taiana M, Lombardi R, Porretta-Serapiglia C, Freschi M, Bonanno S, Marcuzzo S, Caravello F, Bendotti C, Lauria G (2016) ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin. Hum Mol Genet 25(8):1588–1599. https://doi.org/10.1093/hmg/ddw035

    Article  CAS  PubMed  Google Scholar 

  8. Weis J, Katona I, Muller-Newen G, Sommer C, Necula G, Hendrich C, Ludolph AC, Sperfeld AD (2011) Small-fiber neuropathy in patients with ALS. Neurology 76(23):2024–2029. https://doi.org/10.1212/WNL.0b013e31821e553a

    Article  CAS  PubMed  Google Scholar 

  9. Dalla Bella E, Lombardi R, Porretta-Serapiglia C, Ciano C, Gellera C, Pensato V, Cazzato D, Lauria G (2016) Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol 23(2):416–420. https://doi.org/10.1111/ene.12936

    Article  CAS  PubMed  Google Scholar 

  10. Isak B, Tankisi H, Johnsen B, Pugdahl K, Torvin MA, Finnerup NB, Christensen PB, Fuglsang-Frederiksen A (2016) Involvement of distal sensory nerves in amyotrophic lateral sclerosis. Muscle Nerve 54(6):1086–1092. https://doi.org/10.1002/mus.25157

    Article  CAS  PubMed  Google Scholar 

  11. Kakigi R, Watanabe S, Yamasaki H (2000) Pain-related somatosensory evoked potentials. J Clin Neurophysiol 17(3):295–308. https://doi.org/10.1097/00004691-200005000-00007

    Article  CAS  PubMed  Google Scholar 

  12. Yamasaki H, Kakigi R, Watanabe S, Naka D (1999) Effects of distraction on pain perception: magneto- and electro-encephalographic studies. Brain Res Cogn Brain Res 8(1):73–76

    Article  CAS  Google Scholar 

  13. Yamasaki H, Kakigi R, Watanabe S, Hoshiyama M (2000) Effects of distraction on pain-related somatosensory evoked magnetic fields and potentials following painful electrical stimulation. Brain Res Cogn Brain Res 9(2):165–175

    Article  CAS  Google Scholar 

  14. Chen AC, Chapman CR, Harkins SW (1979) Brain evoked potentials are functional correlates of induced pain in man. Pain 6(3):365–374. https://doi.org/10.1016/0304-3959(79)90054-x

    Article  PubMed  Google Scholar 

  15. Obermann M, Katsarava Z, Esser S, Sommer C, He L, Selter L, Yoon MS, Kaube H, Diener HC, Maschke M (2008) Correlation of epidermal nerve fiber density with pain-related evoked potentials in HIV neuropathy. Pain 138(1):79–86. https://doi.org/10.1016/j.pain.2007.11.009

    Article  PubMed  Google Scholar 

  16. Handwerker HO, Kobal G (1993) Psychophysiology of experimentally induced pain. Physiol Rev 73(3):639–671. https://doi.org/10.1152/physrev.1993.73.3.639

    Article  CAS  PubMed  Google Scholar 

  17. Simone IL, Tortelli R, Samarelli V, D'Errico E, Sardaro M, Difruscolo O, Calabrese R, Francesco Vde V, Livrea P, de Tommaso M (2010) Laser evoked potentials in amyotrophic lateral sclerosis. J Neurol Sci 288(1–2):106–111. https://doi.org/10.1016/j.jns.2009.09.023

    Article  PubMed  Google Scholar 

  18. Isak B, Tankisi H, Johnsen B, Pugdahl K, Finnerup NB, Fuglsang-Frederiksen A (2016) Laser and somatosensory evoked potentials in amyotrophic lateral sclerosis. Clin Neurophysiol 127(10):3322–3328. https://doi.org/10.1016/j.clinph.2016.08.008

    Article  PubMed  Google Scholar 

  19. Inui K, Tran TD, Hoshiyama M, Kakigi R (2002) Preferential stimulation of Adelta fibers by intra-epidermal needle electrode in humans. Pain 96(3):247–252

    Article  Google Scholar 

  20. Hara T, Hirayama M, Mizutani Y, Hama T, Hori N, Nakamura T, Kato S, Watanabe H, Sobue G (2013) Impaired pain processing in Parkinson’s disease and its relative association with the sense of smell. Parkinsonism Relat Disord 19(1):43–46. https://doi.org/10.1016/j.parkreldis.2012.06.020

    Article  PubMed  Google Scholar 

  21. Okada A, Nakamura T, Suzuki J, Suzuki M, Hirayama M, Katsuno M, Sobue G (2016) Impaired pain processing correlates with cognitive impairment in Parkinson’s disease. Intern Med 55(21):3113–3118. https://doi.org/10.2169/internalmedicine.55.7067

    Article  PubMed  PubMed Central  Google Scholar 

  22. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J, Swash M (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119(3):497–503. https://doi.org/10.1016/j.clinph.2007.09.143

    Article  PubMed  Google Scholar 

  23. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169(1–2):13–21. https://doi.org/10.1016/s0022-510x(99)00210-5

    Article  CAS  PubMed  Google Scholar 

  24. Valeriani M, Rambaud L, Mauguiere F (1996) Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand. Electroencephalogr Clin Neurophysiol 100(4):343–353. https://doi.org/10.1016/0168-5597(96)95625-7

    Article  CAS  PubMed  Google Scholar 

  25. Ohta K, Takahashi K, Gotoh J, Yamaguchi K, Seki M, Nihei Y, Iwasawa S, Suzuki N (2014) Screening for impaired cognitive domains in a large Parkinson’s disease population and its application to the diagnostic procedure for Parkinson’s disease dementia. Dement Geriatr Cogn Dis Extra 4(2):147–159. https://doi.org/10.1159/000362124

    Article  PubMed  PubMed Central  Google Scholar 

  26. Inui K, Tran TD, Qiu Y, Wang X, Hoshiyama M, Kakigi R (2003) A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations. Neuroscience 120(1):235–248

    Article  CAS  Google Scholar 

  27. Shimizu T, Bokuda K, Kimura H, Kamiyama T, Nakayama Y, Kawata A, Isozaki E, Ugawa Y (2018) Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis. Neurology 90(18):e1578–e1587. https://doi.org/10.1212/wnl.0000000000005424

    Article  PubMed  Google Scholar 

  28. Luigetti M, Conte A, Del Grande A, Bisogni G, Romano A, Sabatelli M (2012) Sural nerve pathology in ALS patients: a single-centre experience. Neurol Sci 33(5):1095–1099. https://doi.org/10.1007/s10072-011-0909-5

    Article  PubMed  Google Scholar 

  29. Irifune M, Kikuchi N, Saida T, Takarada T, Shimizu Y, Endo C, Morita K, Dohi T, Sato T, Kawahara M (2007) Riluzole, a glutamate release inhibitor, induces loss of righting reflex, antinociception, and immobility in response to noxious stimulation in mice. Anesth Analg 104 (6):1415–1421, table of contents. doi:https://doi.org/10.1213/01.ane.0000263267.04198.36

  30. Okamoto M, Gray JD, Larson CS, Kazim SF, Soya H, McEwen BS, Pereira AC (2018) Riluzole reduces amyloid beta pathology, improves memory, and restores gene expression changes in a transgenic mouse model of early-onset Alzheimer’s disease. Transl Psychiatry 8(1):153. https://doi.org/10.1038/s41398-018-0201-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tremolizzo L, Lizio A, Santangelo G, Diamanti S, Lunetta C, Gerardi F, Messina S, La Foresta S, Riva N, Falzone Y, Filippi M, Woolley SC, Sansone VA, Siciliano M, Ferrarese C, Appollonio I (2020) ALS Cognitive Behavioral Screen (ALS-CBS): normative values for the Italian population and clinical usability. Neurol Sci 41(4):835–841. https://doi.org/10.1007/s10072-019-04154-1

    Article  PubMed  Google Scholar 

  32. Poletti B, Solca F, Carelli L, Madotto F, Lafronza A, Faini A, Monti A, Zago S, Calini D, Tiloca C, Doretti A, Verde F, Ratti A, Ticozzi N, Abrahams S, Silani V (2016) The validation of the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Amyotroph Lateral Scler Frontotemporal Degener 17(7–8):489–498. https://doi.org/10.1080/21678421.2016.1183679

    Article  PubMed  Google Scholar 

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Funding

This work was partly supported by a grant from the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yumiko Harada, Tomohiko Nakamura, Masashi Suzuki, Masamichi Ueda & Masahisa Katsuno

  2. Department of Laboratory Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Tomohiko Nakamura

  3. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan

    Masaaki Hirayama

Authors
  1. Yumiko Harada
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  2. Tomohiko Nakamura
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  4. Masamichi Ueda
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Corresponding authors

Correspondence to Tomohiko Nakamura or Masahisa Katsuno.

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Ethical approval

This study was conducted in accordance with the tenets of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects endorsed by the Japanese government. The Ethics Review Committee of Nagoya University School of Medicine approved all aspects of this study (Approval number 2014-0114) and written informed consent for participation was obtained from all subjects.

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The authors declare that they have no conflict of interest.

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Harada, Y., Nakamura, T., Suzuki, M. et al. Impaired pain processing and its association with attention disturbance in patients with amyotrophic lateral sclerosis. Neurol Sci 42, 3327–3335 (2021). https://doi.org/10.1007/s10072-020-05028-7

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  • DOI: https://doi.org/10.1007/s10072-020-05028-7

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