Top

European Journal of Applied Physiology

Published in:

12-11-2023 | Cancer Fatigue | Original Article

Comparison of neuromuscular fatigability amplitude and etiologies between fatigued and non-fatigued cancer patients

Authors: M. Chartogne, A. Rahmani, S. Landry, B. Morel

Published in: European Journal of Applied Physiology | Issue 4/2024

Abstract

Purpose

Cancer-related fatigue (CRF) is the most reported side effect of cancer and its treatments. Mechanisms of CRF are multidimensional, including neuromuscular alterations leading to decreased muscle strength and endurance (i.e., fatigability). Recently, exercise fatigability and CRF have been related, while fatigability mechanisms remain unclear. Traditionally, fatigability is assessed from maximal voluntary contractions (MVC) decrease, but some authors hypothesized that the rate of force development (RFD) determined during a rapid contraction could also be an interesting indicator of functional alterations. However, to our knowledge, no study investigated RFD in cancer patients. The purpose of this study was to determine whether RFD, fatigability amplitude, and etiology are different between fatigued and non-fatigued cancer patients.

Methods

Eighteen participants with cancer, divided in fatigued or non-fatigued groups according their CRF level, completed a 5-min all-out exercise in ankle plantar flexor muscles composed of 62 isometric MVC of 4 s with 1 s rest, to assess fatigability amplitude as the force–time relationship asymptote (F_A). Before and after exercise, fatigability etiologies (i.e., voluntary activation (VA) and evoked forces by electrical stimulation (Db₁₀₀)) were assessed as well as RFD in 50 and 100 ms (RFD₅₀ and RFD₁₀₀, respectively) during rapid contractions.

Results

F_A is significantly lower in fatigued group. Significant differences were found between pre- and post-exercise VA, Db₁₀₀, RFD₅₀, and RFD₁₀₀ for both groups, with no statistical difference between groups.

Conclusion

During treatments, fatigability is higher in fatigued patients; however, the mechanisms of fatigability and RFD alterations are similar in both groups.

Trial registration

ClinicalTrials.gov, NCT04391543, May 2020.

Aagaard P, Simonsen EB, Andersen JL, Magnusson P, Dyhre-Poulsen P (2002) Increased rate of force development and neural drive of human skeletal muscle following resistance training. J Appl Physiol 93(4):1318–1326. https://doi.org/10.1152/japplphysiol.00283.2002CrossRefPubMed

Abdalla LHP, Denadai BS, Bassan NM, Greco CC (2018) Exercise tolerance during muscle contractions below and above the critical torque in different muscle groups. Appl Physiol Nutr Metab 43(2):174–179. https://doi.org/10.1139/apnm-2017-0381CrossRefPubMed

Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, National comprehensive cancer network (2015) Cancer-related fatigue, version 2.2015. J Natl Compr Cancer Netw 13(8):1012–1039. https://doi.org/10.6004/jnccn.2015.0122CrossRef

Boccia G, Dardanello D, Brustio PR, Tarperi C, Festa L, Zoppirolli C, Rainoldi A (2018) Neuromuscular fatigue does not impair the rate of force development in ballistic contractions of submaximal amplitudes. Front Physiol 9:1503. https://doi.org/10.3389/fphys.2018.01503CrossRefPubMedPubMedCentral

Bower JE (2014) Cancer-related fatigue–mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11(10):597–609. https://doi.org/10.1038/nrclinonc.2014.127CrossRefPubMedPubMedCentral

Bower JE, Ganz PA, Irwin MR, Cole SW, Garet D, Petersen L, Crespi CM (2021) Do all patients with cancer experience fatigue? A longitudinal study of fatigue trajectories in women with breast cancer. Cancer. https://doi.org/10.1002/cncr.33327CrossRefPubMed

Brownstein CG, Twomey R, Temesi J, Wrightson JG, Martin T, Medysky ME, Millet GY (2021) Physiological and psychosocial correlates of cancer-related fatigue. J Cancer Surviv. https://doi.org/10.1007/s11764-021-01115-6CrossRefPubMed

Brownstein CG, Twomey R, Temesi J, Medysky ME, Culos-Reed SN, Millet GY (2022) Mechanisms of neuromuscular fatigability in people with cancer-related fatigue. Med Sci Sports Exerc 54(8):1355–1363. https://doi.org/10.1249/MSS.0000000000002919CrossRefPubMed

Burnley M (2009) Estimation of critical torque using intermittent isometric maximal voluntary contractions of the quadriceps in humans. J Appl Physiol 106(3):975–983. https://doi.org/10.1152/japplphysiol.91474.2008CrossRefPubMed

Cai B, Allexandre D, Rajagopalan V, Jiang Z, Siemionow V, Ranganathan VK, Yue GH (2014) Evidence of significant central fatigue in patients with cancer-related fatigue during repetitive elbow flexions till perceived exhaustion. PLoS ONE 9(12):e115370. https://doi.org/10.1371/journal.pone.0115370CrossRefPubMedPubMedCentral

Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Schmitz KH (2019) Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc 51(11):2375–2390. https://doi.org/10.1249/MSS.0000000000002116CrossRefPubMedPubMedCentral

Chartogne M, Rahmani A, Nicolon L, Jubeau M, Morel B (2020) Neuromuscular fatigability amplitude and aetiology are interrelated across muscles. Exp Physiol 105(10):1758–1766. https://doi.org/10.1113/EP088682CrossRefPubMed

Chartogne M, Leclercq A, Beaune B, Boyas S, Forestier C, Martin T, Morel B (2021a) Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol. BMC Cancer 21(1):1140. https://doi.org/10.1186/s12885-021-08831-3CrossRefPubMedPubMedCentral

Chartogne M, Rahmani A, Landry S, Bourgeois H, Peyrot N, Morel B (2021b) Neuromuscular, psychological, and sleep predictors of cancer-related fatigue in cancer patients. Clin Breast Cancer 21(5):425–432. https://doi.org/10.1016/j.clbc.2020.12.002CrossRefPubMed

D’Emanuele S, Maffiuletti NA, Tarperi C, Rainoldi A, Schena F, Boccia G (2021) Rate of force development as an indicator of neuromuscular fatigue: a scoping review. Front Hum Neurosci 15:701916. https://doi.org/10.3389/fnhum.2021.701916CrossRefPubMedPubMedCentral

de Lima FD, Battaglini CL, Chaves SN, Ugliara L, Sarandy J, Lima RM, Bottaro M (2020) Effect of strength training and antioxidant supplementation on perceived and performance fatigability of breast cancer survivors - a randomized, double-blinded, placebo-controlled study. Appl Physiol Nutr Metab. https://doi.org/10.1139/apnm-2020-0166CrossRefPubMed

Donovan KA, Jacobsen PB (2007) Fatigue, depression, and insomnia: evidence for a symptom cluster in cancer. Semin Oncol Nurs 23(2):127–135. https://doi.org/10.1016/j.soncn.2007.01.004CrossRefPubMed

Enoka RM, Stuart DG (1992) Neurobiology of muscle fatigue. J Appl Physiol 72(5):1631–1648. https://doi.org/10.1152/jappl.1992.72.5.1631CrossRefPubMed

Evans JD (1996) Straightforward Statistics for the Behavioral Sciences. Brooks/Cole Pub. Co, Pacific Grove

Gandevia SC (2001) Spinal and supraspinal factors in human muscle fatigue. Physiol Rev 81(4):1725–1789. https://doi.org/10.1152/physrev.2001.81.4.1725CrossRefPubMed

Giesinger JM, Kuijpers W, Young T, Tomaszewski KA, Friend E, Zabernigg A, Aaronson NK (2016) Thresholds for clinical importance for four key domains of the EORTC QLQ-C30: physical functioning, emotional functioning, fatigue and pain. Health Qual Life Outcomes 14:87. https://doi.org/10.1186/s12955-016-0489-4CrossRefPubMedPubMedCentral

Grisold W, Grisold A, Löscher WN (2016) Neuromuscular complications in cancer. J Neurol Sci 367:184–202. https://doi.org/10.1016/j.jns.2016.06.002CrossRefPubMed

Hendrix CR, Housh TJ, Mielke M, Zuniga JM, Camic CL, Johnson GO, Schmidt RJ (2009) Critical torque, estimated time to exhaustion, and anaerobic work capacity from linear and nonlinear mathematical models. Med Sci Sports Exerc 41(12):2185–2190. https://doi.org/10.1249/MSS.0b013e3181ab8cc0CrossRefPubMed

Hucteau E, Mallard J, Pivot X, Schott R, Pflumio C, Trensz P, Hureau TJ (2023) Exacerbated central fatigue and reduced exercise capacity in early-stage breast cancer patients treated with chemotherapy. Eur J Appl Physiol 123(7):1567–1581. https://doi.org/10.1007/s00421-023-05177-5CrossRefPubMedPubMedCentral

Hureau TJ, Romer LM, Amann M (2016) The “sensory tolerance limit”: a hypothetical construct determining exercise performance? Eur J Sport Sci 18(1):13–24. https://doi.org/10.1080/17461391.2016.1252428CrossRefPubMedPubMedCentral

Izquierdo M, Aguado X, Gonzalez R, López JL, Häkkinen K (1999) Maximal and explosive force production capacity and balance performance in men of different ages. Eur J Appl Physiol 79(3):260–267. https://doi.org/10.1007/s004210050504CrossRef

Kent-Braun JA (1997) Noninvasive measures of central and peripheral activation in human muscle fatigue. Muscle Nerve Suppl 5:S98-101CrossRefPubMed

Kisiel-Sajewicz K, Davis MP, Siemionow V, Seyidova-Khoshknabi D, Wyant A, Walsh D, Yue GH (2012) Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue. J Pain Symptom Manag 44(3):351–361. https://doi.org/10.1016/j.jpainsymman.2011.08.007CrossRef

Kluger BM, Krupp LB, Enoka RM (2013) Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology 80(4):409–416. https://doi.org/10.1212/WNL.0b013e31827f07beCrossRefPubMedPubMedCentral

Krüger RL, Aboodarda SJ, Samozino P, Rice CL, Millet GY (2018) Isometric versus dynamic measurements of fatigue: does age matter? A meta-analysis. Med Sci Sports Exerc 50(10):2132–2144. https://doi.org/10.1249/MSS.0000000000001666CrossRefPubMed

MacIntosh BR, Rassier DE (2002) What is fatigue? Can J Appl Physiol 27(1):42–55CrossRefPubMed

Maffiuletti NA, Bizzini M, Widler K, Munzinger U (2010) Asymmetry in quadriceps rate of force development as a functional outcome measure in TKA. Clin Orthop Relat Res 468(1):191–198. https://doi.org/10.1007/s11999-009-0978-4CrossRefPubMed

Maffiuletti NA, Aagaard P, Blazevich AJ, Folland J, Tillin N, Duchateau J (2016) Rate of force development: physiological and methodological considerations. Eur J Appl Physiol 116(6):1091–1116. https://doi.org/10.1007/s00421-016-3346-6CrossRefPubMedPubMedCentral

Millet GY, Martin V, Martin A, Vergès S (2011) Electrical stimulation for testing neuromuscular function: from sport to pathology. Eur J Appl Physiol 111(10):2489–2500. https://doi.org/10.1007/s00421-011-1996-yCrossRefPubMed

Millet GY, Bertrand MF, Lapole T, Féasson L (2023) Measuring objective fatigability and autonomic dysfunction in clinical populations: how and why? Front Sports Act Living. https://doi.org/10.3389/fspor.2023.1140833CrossRefPubMedPubMedCentral

Monod H, Scherrer J (1965) The work capacity of a synergic muscular group. Ergonomics 8(3):329–338. https://doi.org/10.1080/00140136508930810CrossRef

Morel B, Rouffet DM, Saboul D, Rota S, Clémençon M, Hautier CA (2015) Peak torque and rate of torque development influence on repeated maximal exercise performance: contractile and neural contributions. PLoS ONE 10(4):e0119719. https://doi.org/10.1371/journal.pone.0119719CrossRefPubMedPubMedCentral

Morris R, Lewis A (2020) Falls and cancer. Clin Oncol 32(9):569–578. https://doi.org/10.1016/j.clon.2020.03.011CrossRef

Mustian KM, Alfano CM, Heckler C, Kleckner AS, Kleckner IR, Leach CR, Miller SM (2017) Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol 3(7):961–968. https://doi.org/10.1001/jamaoncol.2016.6914CrossRefPubMedPubMedCentral

Neil SE, Klika RJ, Garland SJ, McKenzie DC, Campbell KL (2013) Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors. Support Care Cancer 21(3):873–881. https://doi.org/10.1007/s00520-012-1600-yCrossRefPubMed

Neyroud D, Temesi J, Millet GY, Verges S, Maffiuletti NA, Kayser B, Place N (2015) Comparison of electrical nerve stimulation, electrical muscle stimulation and magnetic nerve stimulation to assess the neuromuscular function of the plantar flexor muscles. Eur J Appl Physiol 115(7):1429–1439. https://doi.org/10.1007/s00421-015-3124-xCrossRefPubMed

Nuttall FQ (2015) Body mass index: obesity, BMI, and health: a critical review. Nutr Today 50(3):117–128. https://doi.org/10.1097/NT.0000000000000092CrossRefPubMedPubMedCentral

Oberoi S, Robinson PD, Cataudella D, Culos-Reed SN, Davis H, Duong N, Sung L (2018) Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: a systematic review and meta-analysis of randomized trials. Crit Rev Oncol Hematol 122:52–59. https://doi.org/10.1016/j.critrevonc.2017.12.011CrossRefPubMed

Place N, Millet GY (2020) Quantification of neuromuscular fatigue what do we do wrong and why? Sports Med 50(3):439–447. https://doi.org/10.1007/s40279-019-01203-9CrossRefPubMed

Prinsen H, van Dijk JP, Zwarts MJ, Leer JWH, Bleijenberg G, van Laarhoven HWM (2015) The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial. J Pain Symptom Manag 49(2):173–182. https://doi.org/10.1016/j.jpainsymman.2014.06.020CrossRef

Schmitt AC, Repka CP, Heise GD, Challis JH, Smith JD (2017) Comparison of posture and balance in cancer survivors and age-matched controls. Clin Biomech 50:1–6. https://doi.org/10.1016/j.clinbiomech.2017.09.010CrossRef

Strojnik V, Komi PV (1998) Neuromuscular fatigue after maximal stretch-shortening cycle exercise. J Appl Physiol 84(1):344–350. https://doi.org/10.1152/jappl.1998.84.1.344CrossRefPubMed

Thomson ZO, Reeves MM (2017) Can weight gain be prevented in women receiving treatment for breast cancer? A systematic review of intervention studies. Obes Rev. https://doi.org/10.1111/obr.12591CrossRefPubMed

Thorlund JB, Michalsik LB, Madsen K, Aagaard P (2008) Acute fatigue-induced changes in muscle mechanical properties and neuromuscular activity in elite handball players following a handball match. Scand J Med Sci Sports 18(4):462–472. https://doi.org/10.1111/j.1600-0838.2007.00710.xCrossRefPubMed

Tucker R (2009) The anticipatory regulation of performance: the physiological basis for pacing strategies and the development of a perception-based model for exercise performance. Br J Sports Med 43(6):392–400. https://doi.org/10.1136/bjsm.2008.050799CrossRefPubMed

Twomey R, Aboodarda SJ, Kruger R, Culos-Reed SN, Temesi J, Millet GY (2017) Neuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigue. Neurophysiol Clinique Clin 47(2):95–110. https://doi.org/10.1016/j.neucli.2017.03.002CrossRef

Twomey R, Martin T, Temesi J, Culos-Reed SN, Millet GY (2018) Tailored exercise interventions to reduce fatigue in cancer survivors: study protocol of a randomized controlled trial. BMC Cancer 18(1):757. https://doi.org/10.1186/s12885-018-4668-zCrossRefPubMedPubMedCentral

van der Leeden M, Huijsmans RJ, Geleijn E, de Rooij M, Konings IR, Buffart LM, Stuiver MM (2018) Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions. Disabil Rehabil 40(4):486–496. https://doi.org/10.1080/09638288.2016.1260647CrossRefPubMed

Varesco G, Luneau E, Féasson L, Lapole T, Rozand V (2022) Very old adults show impaired fatigue resistance compared to old adults independently of sex during a knee-extensors isometric test. Exp Gerontol 161:111732. https://doi.org/10.1016/j.exger.2022.111732CrossRefPubMed

Veni T, Boyas S, Beaune B, Bourgeois H, Rahmani A, Landry S, Morel B (2019) Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study. Support Care Cancer 27(1):229–238. https://doi.org/10.1007/s00520-018-4320-0CrossRefPubMed

Weis J (2011) Cancer-related fatigue: prevalence, assessment and treatment strategies. Expert Rev Pharmacoecon Outcomes Res 11(4):441–446. https://doi.org/10.1586/erp.11.44CrossRefPubMed

Yavuzsen T, Davis MP, Ranganathan VK, Walsh D, Siemionow V, Kirkova J, Yue GH (2009) Cancer-related fatigue: central or peripheral? J Pain Symptom Manag 38(4):587–596. https://doi.org/10.1016/j.jpainsymman.2008.12.003CrossRef

Title: Comparison of neuromuscular fatigability amplitude and etiologies between fatigued and non-fatigued cancer patients
Authors: M. Chartogne
A. Rahmani
S. Landry
B. Morel
Publication date: 12-11-2023
Publisher: Springer Berlin Heidelberg
Keyword: Cancer Fatigue
Published in: European Journal of Applied Physiology / Issue 4/2024
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-023-05347-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comparison of neuromuscular fatigability amplitude and etiologies between fatigued and non-fatigued cancer patients

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Please log in to get access to this content

Other articles of this Issue 4/2024

Cardiorespiratory fitness and submaximal exercise dynamics in normal-weight obesity and metabolically healthy obesity

Hot water immersion is associated with higher thermal comfort than dry passive heating for a similar rise in rectal temperature and plasma interleukin-6 concentration

Hypohydration induced by prolonged cycling in the heat increases biomarkers of renal injury in males

Interrupting sitting acutely attenuates cardiometabolic risk markers in South Asian adults living with overweight and obesity

Association of central blood pressure with an exaggerated blood pressure response to exercise among elite athletes

Development of a prediction equation to estimate lower-limb arterial occlusion pressure with a thigh sphygmomanometer