The Impact of Sub-maximal Exercise on Neuropathic Pain, Inflammation, and Affect Among Adults With Spinal Cord Injury: A Pilot Study

Kendra R Todd, Jan W Van Der Scheer, Jeremy J Walsh, Garett S Jackson, Gabriel U Dix, Jonathan Peter Little, John L K Kramer, Kathleen A Martin Ginis, Kendra R Todd, Jan W Van Der Scheer, Jeremy J Walsh, Garett S Jackson, Gabriel U Dix, Jonathan Peter Little, John L K Kramer, Kathleen A Martin Ginis

Abstract

Introduction: Persons with spinal cord injury (SCI) often report high levels of neuropathic pain (NP) and poor well-being, which may result from increased inflammation. This study examined the impact of sub-maximal aerobic exercise on NP, inflammation and psychological affect among adults with SCI. Methods: Eight active adults with tetraplegia (n-4, AIS A-C) and paraplegia (n = 4, AIS A-C) performed 30-min of arm-crank aerobic exercise and reported their ratings of perceived exertion (RPE) each minute. Measures of NP, affect, and inflammatory cytokines (IL-6, IL-10, IL-1ra, TNF-α) were taken pre-(T0), immediately post-(T1), and 90-min post-exercise (T2). Results: NP decreased between T0 and T1 for tetraplegics (-60%, d = 0.47; CI = -0.32, 2.02) and paraplegics (-16%, d = 0.15; CI = -0.30, 0.90). Correlations between change in cytokines and change in NP were medium-to large for tetraplegics (rs ranged from -0.820 to 0.965) and paraplegics (rs ranged from -0.598 to 0.833). However, the pattern of correlations between change in cytokines and affect was inconsistent between groups. Lower baseline levels of IL-1ra predicted greater decreases in NP immediately post-exercise (r = 0.83, p = 0.01). Conclusion: Sub-maximal exercise can positively impact NP for some persons with SCI. Further experimental research should identify the optimal exercise intensity to reduce NP for persons with SCI, in addition to understanding biomarkers which may predict changes in NP. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03955523.

Keywords: affect; disability; exercise; inflammation; neuropathic pain.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Todd, Van Der Scheer, Walsh, Jackson, Dix, Little, Kramer and Martin Ginis.

Figures

Figure 1
Figure 1
Graphical representation of sub-maximal exercise protocol. Questionnaire symbol = neuropathic pain scale, felt arousal scale and feeling scale; syringe symbol = blood draws.
Figure 2
Figure 2
Average of participants' RPE at 2-min intervals throughout the sub-maximal exercise bout.
Figure 3
Figure 3
Scatterplot of baseline levels of IL-1Ra and changes in neuropathic pain between T0T1.

References

    1. Merksey H, Bogduk N. Part III: pain terms, a current list with definitions and notes on usage. Classification of chronic pain, second edition. IASP Task Force. (1994) 3:15–20.
    1. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and mechanisms. Lancet Neurol. (2014) 13:924–35. 10.1016/S1474-4422(14)70102-4
    1. Burke D, Fullen BM, Stokes D, Lennon O. Neuropathic pain prevalence following spinal cord injury: a systematic review and meta-analysis. Eur J Pain. (2017) 21:29–44. 10.1002/ejp.905
    1. Ekkekakis P. The Measurement of Affect, Mood, and Emotion. A Guide for Health Behavioural Research. 1st ed. New York, NY: Cambridge University Press; (2013). p. 38.
    1. Rodrigues D, Tran Y, Wijesuriya N, Guest R, Middleton J, Craig A. Pain intensity and its association with negative mood states in patients with spinal cord injury. Pain Ther. (2012) 2:113–9. 10.1007/s40122-013-0017-8
    1. Finnerup NB, Johannesen IL, Sindrup SH, Bach FW, Jensen TS. Pain and dysesthesia in patients with spinal cord injury: a postal survey. Spinal Cord. (2001) 39:256–62. 10.1038/sj.sc.3101161
    1. Löfgren M, Norrbrink C. “But I know what works” - patients' experience of spinal cord injury neuropathic pain management. Disabil Rehabil. (2012) 34:2139–47. 10.3109/09638288.2012.676146
    1. Budh CN, Lundeberg T. Non-pharmacological pain-relieving therapies in individuals with spinal cord injury: a patient perspective. Comp Therap Med. (2004) 12:189–97. 10.1016/j.ctim.2004.10.003
    1. Todd KR, Martin Ginis KA. An examination of diurnal variations in neuropathic pain and affect, on exercise and non-exercise days, in adults with spinal cord injury. Spinal Cord Ser Cases. (2018) 4:1. 10.1038/s41394-018-0130-3
    1. Martin Ginis KA, Latimer AE. The effects of single bouts of body-weight supported treadmill training on the feeling states of people with spinal cord injury. Spinal Cord. (2007) 45:112–5. 10.1038/sj.sc.3101911
    1. Guy SD, Mehta S, Casalino A, Côté I, Kras-Dupuis A, Moulin DE, et al. . The canpain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord: recommendations for treatment. Spinal Cord. (2016) 54:S14–23. 10.1038/sc.2016.90
    1. Norrbrink C, Lindberg T, Wahman K, Bjerkefors A. Effects of an exercise programme on musculoskeletal and neuropathic pain after spinal cord injury - results from a seated double-poling ergometer study. Spinal Cord. (2012) 50:457–61. 10.1038/sc.2011.160
    1. Woolf CJ, Decosterd I. Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients. Pain. (1999) 82(Suppl. 1):S141–7. 10.1016/S0304-3959(99)00148-7
    1. Rice D, Nijs J, Kosek E, Wideman T, Hasenbring MI, Koltyn K, et al. . Exercise-induced hypoalgesia in pain-free and chronic pain populations: state of the art and future directions. J Pain. (2019) 20:1249–66. 10.1016/j.jpain.2019.03.005
    1. Lima LV, Abner TS, Sluka KA. Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena. J Physiol. (2017) 595:4141–50. 10.1113/JP273355
    1. Wrigley PJ, Press SR, Gustin SM, Macefield VG, Gandevia SC, Cousins MJ, et al. . Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury. PAIN. (2009) 141:52–9. 10.1016/j.pain.2008.10.007
    1. Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. PAIN. (2018) 159:595–602. 10.1097/j.pain.0000000000001122
    1. Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. (2004) 361:184–7. 10.1016/j.neulet.2003.12.007
    1. Allison DJ, Thomas A, Beaudry K, Ditor DS. Targeting inflammation as a treatment modality for neuropathic pain in spinal cord injury: a randomized clinical trial. J Neuroinflammation. (2016) 13:1. 10.1186/s12974-016-0625-4
    1. Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol. (1999) 515:287–91. 10.1111/j.1469-7793.1999.287ad.x
    1. Brown WMC, Davison GW, McClean CM, Murphy MH. A systematic review of the acute effects of exercise on immune and inflammatory indices in untrained adults. Br J Sports Med. (2001) 1:1–10. 10.1186/s40798-015-0032-x
    1. Hoffman MD, Shepanski MA, Ruble SB, Valic Z, Buckwalter JB, Clifford PS. Intensity and duration threshold for aerobic exercise-induced analgesia to pressure pain. Arch Phys Med Rehabil. (2004) 85:1183–7. 10.1016/j.apmr.2003.09.010
    1. Ekkekakis P, Parfitt G, Petruzzello SJ. The pleasure and displeasure people feel when they exercise at different intensities. Sports Med. (2011) 41:641–71.
    1. Teasell RW, Arnold JM, Krassioukov A, Delaney GA. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehab. (2000) 81:506–16. 10.1053/mr.2000.3848
    1. Kouda K, Furusawa K, Sugiyama H, Sumiya T, Ito T, Tajima F, et al. . Does 20-min arm crank ergometer exercise increase plasma interleukin-6 in individuals with cervical spinal cord injury? Eur J Appl Physiol. (2012) 112:597–604. 10.1007/s00421-011-2004-2
    1. Paulson TAW, Goosey-Tolfrey VL, Lenton JP, Leicht CA, Bishop NC. Spinal cord injury level and the circulating cytokine response to strenuous exercise. Med Sci Sports Exerc. (2013) 45:1649–55. 10.1249/MSS.0b013e31828f9bbb
    1. Mee-Inta O, Zhao ZW, Kuo YM. Physical exercise inhibits inflammation and microglial activation. Cells. (2019) 8:691. 10.3390/cells8070691
    1. Martin Ginis KA, Van Der Scheer JW, Latimer-Cheung AE, Barrow A, Bourne C, Carruthers P, et al. . Evidence-based scientific exercise guidelines for adults with spinal cord injury: an update and a new guideline. Spinal Cord. (2018) 56:308–21. 10.1038/s41393-017-0017-3
    1. Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes NAM, et al. . Exercise and acute cardiovascular events: placing the risks into perspective a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation. (2007) 115:2358–68. 10.1161/CIRCULATIONAHA.107.181485
    1. Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the neuropathic pain scale. Neurology. (1997) 48:332–8. 10.1212/WNL.48.2.332
    1. Hardy CJ, Rejeski WJ. Not what, but how one feels: the measurement of affect during exercise. J Sport Exerc Psychol. (1989) 11:304–17. 10.1123/jsep.11.3.304
    1. Svebak S, Murgatroyd S. Metamotivational dominance. A multimethod validation of reversal theory constructs. J Pers Soc Psychol. (1985) 48:107–16. 10.1037/0022-3514.48.1.107
    1. Watson D, Clark LA. Measurement and mismeasurement of mood: recurrent and emergent issues. J Pers Assess. (1997) 68:267–96. 10.1207/s15327752jpa6802_4
    1. Borg GAV. Psychophysical bases of perceived exertion. Med Sci Sport Exerc. (1982) 14:377. 10.1249/00005768-198205000-00012
    1. Hutchinson MJ, Valentino SE, Totosy de Zepetnek J, MacDonald MJ, Goosey-Tolfrey VL. Perceptually regulated training does not influence the differentiated RPE response following 16-weeks of aerobic exercise in adults with spinal cord injury. Appl Physiol Nutr Metab. (2020) 45:129–34. 10.1139/apnm-2019-0062
    1. Claydon VE, Hol AT, Eng JJ, Krassioukov AV. Cardiovascular responses and postexercise hypotension after arm cycling exercise in subjects with spinal cord injury. Arch Phys Med Rehabil. (2006) 87:1106–14. 10.1016/j.apmr.2006.05.011
    1. Lasko-McCarthey P, Davis JA. Protocol dependency of VO2max during arm cycle ergometry in males with quadriplegia. Med Sci Sports Exerc. (1991) 23:1097–101. 10.1249/00005768-199109000-00016
    1. Martel G, Noreau L, Jobin J. Physiological responses to maximal exercise on arm cranking and wheelchair ergometer with paraplegics. Paraplegia. (1991) 29:447–56. 10.1038/sc.1991.61
    1. Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol. (2013) 4:863. 10.3389/fpsyg.2013.00863
    1. Cohen J. Statistical Power Analysis for the Behavioural Sciences. 2nd ed. New York, NY: Academic Press; (1977). p. 8.
    1. Widerström-Noga E. Neuropathic pain and spinal cord injury: phenotypes and pharmacological management. Drugs. (2017) 77:967–84. 10.1007/s40265-017-0747-8
    1. Celik EC, Erhan B, Lakse E. The clinical characteristics of neuropathic pain in patients with spinal cord injury. Spinal Cord. (2012) 50:585–9. 10.1038/sc.2012.26
    1. Lind E, Ekkekakis P, Vazou S. The affective impact of exercise intensity that slightly exceeds the preferred level. J Health Psychol. (2008) 13:464–8. 10.1177/1359105308088517
    1. Ekkekakis P, Zenko Z, Ladwig M, Hartman M. Affective Determinants of Health Behavior. New York, NY: Oxford University Press; (2018). p. 237.
    1. Whiteside A, Hansen S, Chaudhuri A. Exercise lowers pain threshold in chronic fatigue syndrome. Pain. (2004) 109:497–9. 10.1016/j.pain.2004.02.029
    1. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. (2008) 88:1379–406. 10.1152/physrev.90100.2007
    1. Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev. (2006) 41:6–33.
    1. Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. (2008) 2008:109502. 10.1155/2008/109502
    1. Bixby WR, Spalding TW, Hatfield BD. Temporal dynamics and dimensional specificity of the affective response to exercise of varying intensity: differing pathways to a common outcome. J Sport Exerc Psychol. (2001) 23:171–90. 10.1123/jsep.23.3.171
    1. Ma CA, Rajandran SN, Liu J, Wong SB, Leung YY. The association of plasma IL-1Ra and related cytokines with radiographic severity of early knee osteoarthritis. Osteoarthr Cartil. (2020) 2:100046. 10.1016/j.ocarto.2020.100046
    1. Martin Ginis KA, van der Scheer JW, Todd KR, Davis JC, Gaudet S, Hoekstra F, et al. . A pragmatic randomized controlled trial testing the effects of the international scientific SCI exercise guidelines on SCI chronic pain: protocol for the EPIC-SCI trial. Spinal Cord. (2020) 58:746–54. 10.1038/s41393-020-0519-2
    1. Amur S, LaVange L, Zineh I, Buckman-Garner S, Woodcock J. Biomarker qualification: toward a multiple stakeholder framework for biomarker development, regulatory acceptance, and utilization. Curr Clin Pharmacol. (2015) 98:34–46. 10.1002/cpt.136
    1. Kramer JL, Minhas NK, Jutzeler CR, Erskine EL, Liu LJ, Ramer MS. Neuropathic pain following traumatic spinal cord injury: models, measurement, and mechanisms. J Neurosci Res. (2017) 95:1295–306. 10.1002/jnr.23881
    1. Widerström-Noga E, Biering-Sørensen F, Bryce TN, Cardenas DD, Finnerup NB, Jensen MP, et al. . The international spinal cord injury pain basic data set (version 2.0). Spinal Cord. (2014) 52:282–6. 10.1038/sc.2014.4
    1. Gillum TL, Kuennen MR, Schneider S, Moseley P. A review of sex differences in immune function after aerobic exercise. Exerc Immunol Rev. (2011) 17:104–21.
    1. Wiesenfeld-Hallin Z. Sex differences in pain perception. Gend Med. (2005) 2:137–45. 10.1016/S1550-8579(05)80042-7
    1. Singh A, Tetreault L, Kalsi S, Aria R, Michael N, Fehlings G, et al. . Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol. (2014) 6:309. 10.2147/CLEP.S68889

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