Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Relationships between cardiovascular disease risk, neuropathic pain, mental health, and autonomic function in chronic spinal cord injury


Study design

Multicentre, cross-sectional study.


To determine if clinical measures of poor mental health (MH-) and neuropathic pain (NP) are related to increased CVD risk in individuals with chronic spinal cord injury (SCI), and further elucidate the relationships between CVD risk, autonomic function, NP, and MH-.


Eight SCI rehabilitation centres in the Netherlands.


Individuals (n = 257) with a traumatic, chronic (≥10 yrs) SCI, with age at injury between 18–35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. CVD risk was calculated using Framingham risk score. NP was inferred using The Douleur Neuropathique 4 clinical examination, and MH- was assessed using the five-item Mental Health Inventory questionnaire. Cardiovascular autonomic function was determined from peak heart rate during maximal exercise (HRpeak).


There was a high prevalence of both NP (39%) and MH- (45%) following SCI. MH- was significantly correlated with an adverse CVD risk profile (r = 0.174; p = 0.01), increased the odds of adverse 30-year CVD risk by 2.2 (CI 0.92–2.81, p = 0.02), and is an important variable in determining CVD risk (importance=0.74, p = 0.05). Females (p = 0.05) and those with a higher HRpeak (p = 0.046) tended to be more likely to have NP.


Clinical measures of MH-, but not NP, are important factors for increased CVD risk following SCI. NP tended to be more prevalent in those with more preserved cardiovascular autonomic function. The interrelationships between secondary consequences of SCI are complex and need further exploration.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Akaike Information Criterion model-averaged importance of predictors of CVD risk.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.


  1. Burns S, Biering-Sørensen F, Donovan W, Graves D, Jha A, Johansen M, et al. International Standards for Neurological Classification of Spinal Cord Injury, Revised 2011. Top Spinal Cord Inj Rehabil. 2012;18:85–99.

    Article  PubMed  Google Scholar 

  2. Krassioukov A. Autonomic function following cervical spinal cord injury. Respir Physiol Neurobiol. 2009;169:157–64.

    Article  PubMed  Google Scholar 

  3. Furlan JC, Fehlings MG, Shannon P, Norenberg MD, Krassioukov AV. Descending Vasomotor Pathways in Humans: Correlation between Axonal Preservation and Cardiovascular Dysfunction after Spinal Cord Injury. J Neurotrauma [Internet]. 2003;20. Available from:

  4. Claydon V, Krassioukov AV. Orthostatic Hypotension and Autonomic Pathways after Spinal Cord Injury. J Neurotrauma. 2006;23:1713–25.

    Article  PubMed  Google Scholar 

  5. Ravensbergen HJC, Post MWM, Slootman HJ, Claydon VE, van der Woude LHV, Groot S. Cardiovascular function after spinal cord injury: prevalence and progression of dysfunction during inpatient rehabilitation and 5 years following discharge. Neurorehabil Neural Repair. 2013;28:219–29.

    Article  PubMed  Google Scholar 

  6. Garshick E, Kelley A, Cohen SA, Garrison A, Tun CG, Gagnon D, et al. A prospective assessment of mortality in chronic spinal cord injury. Spinal Cord. 2005;43:408–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cragg JJ, Stone JA, Krassioukov AV. Management of Cardiovascular Disease Risk Factors in Individuals with Chronic Spinal Cord Injury: An Evidence-Based Review. J Neurotrauma. 2012;29:1999–2012.

    Article  PubMed  Google Scholar 

  8. Dorton MC, Lucci VEM, de Groot S, Loughin TM, Cragg JJ, Kramer JK, et al. Evaluation of cardiovascular disease risk in individuals with chronic spinal cord injury. Spinal Cord. 2021;59:716–29.

    Article  PubMed  Google Scholar 

  9. 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. Williams R, Murray A. Prevalence of depression after spinal cord injury: A meta-analysis. Arch Phys Med Rehabil. 2015;96:133–40.

    Article  PubMed  Google Scholar 

  11. Cragg JJ, Noonan VK, Noreau L, Borisoff JF, Kramer JK. Neuropathic pain, depression, and cardiovascular disease: A national multicenter study. Neuroepidemiology. 2015;44:130–7.

    Article  PubMed  Google Scholar 

  12. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxell J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005;114:29–36.

    Article  PubMed  Google Scholar 

  13. Berwick DM, Murphy JM, Goldman PA, Ware JE, Barsky AJ, Weinstein MC. Performance of a Five-Item Mental Health Screening. Test. 1991;29:169–76.

    CAS  Google Scholar 

  14. Fayaz A, Ayis S, Panesar SS, Langford RM, Donaldson LJ. Assessing the relationship between chronic pain and cardiovascular disease: A systematic review and meta-analysis. Scand J Pain. 2016;13:76–90.

    Article  PubMed  Google Scholar 

  15. Oliveira CB, Maher CG, Franco MR, Kamper SJ, Williams CM, Silva FG, et al. Co-occurrence of Chronic Musculoskeletal Pain and Cardiovascular Diseases: A Systematic Review with Meta-Analysis. Pain Med. 2020;21:1106–21.

    Article  PubMed  Google Scholar 

  16. Siddall PJ, Mcclelland JM, Rutkowski SB, Cousins MJ. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003;103:249–57.

    Article  PubMed  Google Scholar 

  17. Davidoff G, Roth E, Guarracini M, Yarkony G, Sliwa J. Function-limiting dysesthetic pain syndrome among traumatic spinal cord injury patients: a cross-sectional study. Pain.1987;29:39–48.

    Article  PubMed  Google Scholar 

  18. Vall J, Mauricio C, Costa DC, Jesus T De, Santos T, Bovy S, et al. Neuropathic pain characteristics in patients from Curitiba (Brazil) with spinal cord injury. Arq Neuropsiquiatr. 2011;69:64–8.

  19. Werhagen L, Budh CN, Hultling C, Molander C. Neuropathic pain after traumatic spinal cord injury – relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord. 2004;665–73.

  20. Krassioukov AV, Bunge RP, Pucket WR, Bygrave MA. The changes in human spinal sympathetic preganglionic neurons after spinal cord injury. Spinal Cord. 1999;37:6–13.

    Article  CAS  PubMed  Google Scholar 

  21. Walters ET. How is chronic pain related to sympathetic dysfunction and autonomic dysreflexia following spinal cord injury? Auton Neurosc. 2018;209:79–89.

  22. Alberto J, Manresa B, Susanne N, Finnerup B, Lauge I, Biering-sørensen F, et al. Central sensitization in spinal cord injured humans assessed by reflex receptive fields. Clin Neurophysiol. 2014;125:352–62.

    Article  Google Scholar 

  23. Arnold JMO, Feng QP, Delaney GA, Teasell RW. Autonomic dysreflexia in tetraplegic patients: Evidence for α-adrenoceptor hyper-responsiveness. Clin Auton Res. 1995;5:267–70.

    Article  CAS  PubMed  Google Scholar 

  24. Saunders LL, Krause JS, Focht KL. A longitudinal study of depression in survivors of spinal cord injury. Spinal Cord. 2012;50:72–7.

    Article  CAS  PubMed  Google Scholar 

  25. Shao M, Lin X, Jiang D, Tian H, Xu Y, Wang L, et al. Depression and cardiovascular disease: Shared molecular mechanisms and clinical implications. Psychiatry Res. 2020;285:112802.

  26. Cragg JJ, Noonan VK, Krassioukov A, Borisoff J. Cardiovascular disease and spinal cord injury: Results from a national population health survey. Neurology. 2013;81:723–8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Adriaansen JJE, Van Asbeck FWA, Lindeman E, Van Der Woude LHV, De Groot S, Post MWM. Secondary health conditions in persons with a spinal cord injury for at least 10 years: Design of a comprehensive long-term cross-sectional study. Disabil Rehabil. 2013;35:1104–10.

    Article  PubMed  Google Scholar 

  28. Kong H, West S. WMA Declaration of Helsinki- Ethical Principles for Medical Research Involving Human Subjects. World Med Assoc. 2013;0:1–4.

    Google Scholar 

  29. West CR, Mills P, Krassioukov AV. Influence of the neurological level of spinal cord injury on cardiovascular outcomes in humans: a meta-analysis. Spinal Cord. 2012;50:484–92.

    Article  CAS  PubMed  Google Scholar 

  30. Rivera-Riquelme M, Piqueras JA, Cuijpers P. The Revised Mental Health Inventory-5 (MHI-5) as an ultra-brief screening measure of bidimensional mental health in children and adolescents. Psychiatry Res. 2019;274:247–53.

    Article  PubMed  Google Scholar 

  31. Van Leeuwen CMC, Van Der Woude LHV, Post MWM. Validity of the mental health subscale of the SF-36 in persons with spinal cord injury. Spinal Cord. 2012;50:707–10.

    Article  PubMed  Google Scholar 

  32. Ravensbergen HJR, Groot S, Post MW, Bongers-Janssen HM, Woude LH, Claydon VE. Is There an Association Between Markers of Cardiovascular Autonomic Dysfunction at Discharge From Rehabilitation and Participation 1 and 5 Years Later in Individuals With Spinal Cord Injury?. Arch Phys Med Rehabil. 2016;97:1431–9.

    Article  Google Scholar 

  33. D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: The Framingham heart study. Circulation. 2008;117:743–53.

    Article  PubMed  Google Scholar 

  34. Pencina MJ, D’Agostino RB, Larson MG, Massaro JM, Vasan RS. Predicting the 30-year risk of cardiovascular disease: The framingham heart study. Circulation. 2009;119:3078–84.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bucciarelli V, Caterino AL, Bianco F, Caputi CG, Salerni S, Sciomer S, et al. Depression and cardiovascular disease: The deep blue sea of women’s heart. Trends Cardiovasc Med. 2020;30:170–6.

    Article  PubMed  Google Scholar 

  36. Khandelwal A, Shafer LA, Ethans K. Does severity of spinal cord injury predict likelihood of suffering chronically from severe depression and anxiety? Spinal Cord Ser Cases. 2022;8:1–5.

    Article  Google Scholar 

  37. Tate DG, Kalpakjian CZ, Forchheimer MB. Quality of life issues in individuals with spinal cord injury. Arch Phys Med Rehabil. 2002;83:18–25.

    Article  Google Scholar 

  38. Cragg JJ, Warner FM, Shupler MS, Jutzeler CR, Cashman N, Whitehurst DGT, et al. Text Table 1 Interview questions for Survey on Living with Neurological Conditions in Canada (SLNCC). Heal Rep. Stat Can. 2018;29:11–6.

    Google Scholar 

  39. Werhagen L, Hultling C, Molander C. The prevalence of neuropathic pain after non-traumatic spinal cord lesion. Spinal Cord. 2007;45:609–15.

    Article  CAS  PubMed  Google Scholar 

  40. Lee SE, Greenough EK, Oancea P, Scheinfeld AR, Douglas AM, Gaudet AD. Sex differences in pain: Spinal cord injury in female and male mice elicits behaviors related to neuropathic pain. J Neurotrauma. 2023;40:833–844.

  41. Adriaansen JJE, Douma-Haan Y, van Asbeck FWA, van Koppenhagen CF, de Groot S, van Asbeck FWA, et al. Prevalence of hypertension and associated risk factors in people with long-term spinal cord injury living in the Netherlands. Disabil Rehabil. 2017;39:919–27.

    Article  PubMed  Google Scholar 

Download references


We are grateful to Dr. Vera-Ellen Lucci for her contribution to this work.



This study is part of the Dutch ALLRISC research program and is supported financially by ZonMw Rehabilitation program and Fonds NutsOhra, grant no. 89000006.

Author information

Authors and Affiliations



JKK, MCD, and VEC conceived the idea for the study. MWMP and SDG designed the study protocol and collected the data. MCD and VEC analysed the data. JKK, MWMP, and SDG assisted in interpreting the results. MCD and VEC wrote the manuscript. VEC supervised the research. All authors contributed to the critical revision of the manuscript.

Corresponding author

Correspondence to Victoria E. Claydon.

Ethics declarations

Competing interests

The authors declare no competing interests.


We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dorton, M.C., Kramer, J.K., de Groot, S. et al. Relationships between cardiovascular disease risk, neuropathic pain, mental health, and autonomic function in chronic spinal cord injury. Spinal Cord 61, 548–555 (2023).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links