Increased Headache Prevalence in Patients with Neuropathic Pain
Main Article Content
Abstract
Patients with neuropathic symptoms, including neuropathic pain and autonomic symptoms, frequently have headaches. They were evaluated by neurologists and underwent a diagnostic skin biopsy for small fiber neuropathy at Massachusetts General Hospital from 2018-2020. The correlations of neuropathic pain, autonomic symptoms, and headaches were examined. The results of skin biopsy, nerve conduction velocity/electromyography, and autonomic function testing were analyzed.
Most (73.8%) of the patients who underwent a skin biopsy were females. The mean age was 46.8. Most patients had neuropathic pain (61.3%). In addition, autonomic symptoms were present in 48.0% of patients. The prevalence of headaches was 48.2% in the whole study cohort, with 73.2% of headaches fulfilling the criteria of migraine.
We detected female dominance in patients who had headaches and migraine but not in the neuropathic pain and autonomic symptom groups. The correlations between headaches, migraine, neuropathic pain, and autonomic symptoms were examined. There were statistical correlations between headaches and neuropathic pain (p< 0.0001) and autonomic symptoms (p< 0.01). Similar trends were detected for migraine with neuropathic pain but not with autonomic symptoms.
The symptomatology was analyzed with the results of skin biopsy, nerve conduction velocity/electromyography, and autonomic function testing. Only autonomic symptoms have a significant positive correlation with positive autonomic function testing results. Otherwise, the results of skin biopsy, nerve conduction velocity/electromyography, and autonomic function testing had no significant correlation with neuropathic pain, headaches, and migraine. The lack of positive correlations between peripheral neuropathy studies and headaches suggests centralized mechanisms likely mediate headaches in patients with neuropathic pain and autonomic symptoms.
Keywords:
headache, neuropathic pain, autonomic symptoms, migraine, small fiber neuropathy
Article Details
How to Cite
CHENG, Jennifer R et al.
Increased Headache Prevalence in Patients with Neuropathic Pain.
Medical Research Archives, [S.l.], v. 12, n. 11, nov. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6075>. Date accessed: 12 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i11.6075.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Hovaguimian A, Gibbons CH. Diagnosis and treatment of pain in small-fiber neuropathy. Curr Pain Headache Rep. Jun 2011;15(3):193-200. doi:10.1007/s11916-011-0181-7
2. Devigili G, Cazzato D, Lauria G. Clinical diagnosis and management of small fiber neuropathy: an update on best practice. Expert Rev Neurother. Sep 2020;20(9):967-980. doi:10.1080/14737175.2020.1794825
3. Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. Feb 16 2017;3:17002. doi:10.1038/nrdp.2017.2
4. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. Aug 2010;9(8):807-19. doi:10.1016/S1474-4422(10)70143-5
5. Goldberger JJ, Arora R, Buckley U, Shivkumar K. Autonomic Nervous System Dysfunction: JACC Focus Seminar. J Am Coll Cardiol. Mar 19 2019;73(10):1189-1206. doi:10.1016/j.jacc.2018.12.064
6. Bakkers M, Faber CG, Hoeijmakers JG, Lauria G, Merkies IS. Small fibers, large impact: quality of life in small-fiber neuropathy. Muscle Nerve. Mar 2014;49(3):329-36. doi:10.1002/mus.23910
7. Dydyk AM, Givler A. Central Pain Syndrome. StatPearls. 2023.
8. Ducreux D, Attal N, Parker F, Bouhassira D. Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain. Apr 2006;129(Pt 4):963-76. doi:10.1093/brain/awl016
9. Clauw DJ. Fibromyalgia: a clinical review. JAMA. Apr 16 2014;311(15):1547-55. doi:10.1001/jama.2014.3266
10. Harper DE, Schrepf A, Clauw DJ. Pain Mechanisms and Centralized Pain in Temporomandibular Disorders. J Dent Res. Sep 2016;95(10):1102-8. doi:10.1177/0022034516657070
11. Dydyk AM, Munakomi S. Thalamic Pain Syndrome. StatPearls. 2023.
12. Farhad K, Oaklander AL. Fibromyalgia and small-fiber polyneuropathy: What's in a name? Muscle Nerve. Nov 2018;58(5):611-613. doi:10.1002/mus.26179
13. Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. Oct 2010;33(10):2285-93. doi:10.2337/dc10-1303
14. Raasing LRM, Vogels OJM, Veltkamp M, van Swol CFP, Grutters JC. Current View of Diagnosing Small Fiber Neuropathy. J Neuromuscul Dis. 2021;8(2):185-207. doi:10.3233/JND-200490
15. Iyengar S, Johnson KW, Ossipov MH, Aurora SK. CGRP and the Trigeminal System in Migraine. Headache. May 2019;59(5):659-681. doi:10.1111/head.13529
16. Edvinsson JCA, Vigano A, Alekseeva A, et al. The fifth cranial nerve in headaches. J Headache Pain. Jun 5 2020;21(1):65. doi:10.1186/s10194-020-01134-1
17. Messlinger K, Fischer MJ, Lennerz JK. Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine. Keio J Med. 2011;60(3):82-9. doi:10.2302/kjm.60.82
18. Terrier LM, Fontaine D. Intracranial nociception. Rev Neurol (Paris). Sep 2021;177(7):765-772. doi:10.1016/j.neurol.2021.07.012
19. Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. Feb 5 2014;348:f7656. doi:10.1136/bmj.f7656
20. Wig R, Oakley CB. Dysautonomia and Headache in the Pediatric Population. Headache. Oct 2019;59(9):1582-1588. doi:10.1111/head.13659
21. Haensch CA, Tosch M, Katona I, Weis J, Isenmann S. Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome. Muscle Nerve. Dec 2014;50(6):956-61. doi:10.1002/mus.24245
22. Lacomis D. Small-fiber neuropathy. Muscle Nerve. Aug 2002;26(2):173-88. doi:10.1002/mus.10181
23. Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. Aug 2010;17(8):1010-8. doi:10.1111/j.1468-1331.2010.02969.x
24. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. Jan 2018;38(1):1-211. doi:10.1177/0333102417738202
25. Goldstein DS, Cheshire WP, Jr. The autonomic medical history. Clin Auton Res. Aug 2017;27(4):223-233. doi:10.1007/s10286-017-0425-7
26. Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. Nov 2013;154(11):2310-6. doi:10.1016/j.pain.2013.06.001
27. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. Jul 2010;17(7):903-12, e44-9. doi:10.1111/j.1468-1331.2010.03023.x
28. McCorquodale D, Smith AG. Clinical electrophysiology of axonal polyneuropathies. Handb Clin Neurol. 2019;161:217-240. doi:10.1016/b978-0-444-64142-7.00051-5
29. Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol. 2013;115:115-36. doi:10.1016/B978-0-444-52902-2.00007-2
30. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. Apr 2014;155(4):654-662. doi:10.1016/j.pain.2013.11.013
31. Blyth FM. Global burden of neuropathic pain. Pain. Mar 2018;159(3):614-617. doi:10.1097/j.pain.0000000000001127
32. Themistocleous AC, Ramirez JD, Shillo PR, et al. The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy. Pain. May 2016;157(5):1132-1145. doi:10.1097/j.pain.0000000000000491
33. Walk D. Role of skin biopsy in the diagnosis of peripheral neuropathic pain. Curr Pain Headache Rep. Jun 2009;13(3):191-6. doi:10.1007/s11916-009-0033-x
34. Gylfadottir SS, Christensen DH, Nicolaisen SK, et al. Diabetic polyneuropathy and pain, prevalence, and patient characteristics: a cross-sectional questionnaire study of 5,514 patients with recently diagnosed type 2 diabetes. Pain. Mar 2020;161(3):574-583. doi:10.1097/j.pain.0000000000001744
35. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. Jun 2008;136(3):380-387. doi:10.1016/j.pain.2007.08.013
36. Leung A. Addressing chronic persistent headaches after MTBI as a neuropathic pain state. J Headache Pain. Jun 19 2020;21(1):77. doi:10.1186/s10194-020-01133-2
37. Ashina S, Bendtsen L, Lyngberg AC, Lipton RB, Hajiyeva N, Jensen R. Prevalence of neck pain in migraine and tension-type headache: a population study. Cephalalgia. Mar 2015;35(3):211-9. doi:10.1177/0333102414535110
38. Barmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management. Curr Neurol Neurosci Rep. Mar 19 2019;19(5):20. doi:10.1007/s11910-019-0937-8
39. Vincent MB. Headache and neck. Curr Pain Headache Rep. Aug 2011;15(4):324-31. doi:10.1007/s11916-011-0195-1
40. Iser C, Arca K. Headache and Autonomic Dysfunction: a Review. Curr Neurol Neurosci Rep. Oct 2022;22(10):625-634. doi:10.1007/s11910-022-01225-3
41. Waliszewska-Prosol M, Straburzynski M, Czapinska-Ciepiela EK, Nowaczewska M, Gryglas-Dworak A, Budrewicz S. Migraine symptoms, healthcare resources utilization and disease burden in a large Polish migraine cohort : Results from 'Migraine in Poland'-a nationwide cross-sectional survey. J Headache Pain. Apr 11 2023;24(1):40. doi:10.1186/s10194-023-01575-4
42. Dodick DW. A Phase-by-Phase Review of Migraine Pathophysiology. Headache. May 2018;58 Suppl 1:4-16. doi:10.1111/head.13300
43. Barizien N, Le Guen M, Russel S, Touche P, Huang F, Vallee A. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep. Jul 7 2021;11(1):14042. doi:10.1038/s41598-021-93546-5
44. Gazerani P, Cairns BE. Dysautonomia in the pathogenesis of migraine. Expert Rev Neurother. Feb 2018;18(2):153-165. doi:10.1080/14737175.2018.1414601
45. Myers MI, Peltier AC. Uses of skin biopsy for sensory and autonomic nerve assessment. Curr Neurol Neurosci Rep. Jan 2013;13(1):323. doi:10.1007/s11910-012-0323-2
46. Johnson SA, Shouman K, Shelly S, et al. Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability. Neurology. Nov 30 2021;97(22):e2236-e2247. doi:10.1212/WNL.0000000000012894
47. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. Mar 2011;152(3 Suppl):S2-S15. doi:10.1016/j.pain.2010.09.030
48. Packard RC. The relationship of neck injury and post-traumatic headache. Curr Pain Headache Rep. Aug 2002;6(4):301-7. doi:10.1007/s11916-002-0051-4
49. Chen G, Zhang YQ, Qadri YJ, Serhan CN, Ji RR. Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain. Neuron. Dec 19 2018;100(6):1292-1311. doi:10.1016/j.neuron.2018.11.009
50. Sommer C, Leinders M, Uceyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. Mar 2018;159(3):595-602. doi:10.1097/j.pain.0000000000001122
2. Devigili G, Cazzato D, Lauria G. Clinical diagnosis and management of small fiber neuropathy: an update on best practice. Expert Rev Neurother. Sep 2020;20(9):967-980. doi:10.1080/14737175.2020.1794825
3. Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. Feb 16 2017;3:17002. doi:10.1038/nrdp.2017.2
4. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. Aug 2010;9(8):807-19. doi:10.1016/S1474-4422(10)70143-5
5. Goldberger JJ, Arora R, Buckley U, Shivkumar K. Autonomic Nervous System Dysfunction: JACC Focus Seminar. J Am Coll Cardiol. Mar 19 2019;73(10):1189-1206. doi:10.1016/j.jacc.2018.12.064
6. Bakkers M, Faber CG, Hoeijmakers JG, Lauria G, Merkies IS. Small fibers, large impact: quality of life in small-fiber neuropathy. Muscle Nerve. Mar 2014;49(3):329-36. doi:10.1002/mus.23910
7. Dydyk AM, Givler A. Central Pain Syndrome. StatPearls. 2023.
8. Ducreux D, Attal N, Parker F, Bouhassira D. Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain. Apr 2006;129(Pt 4):963-76. doi:10.1093/brain/awl016
9. Clauw DJ. Fibromyalgia: a clinical review. JAMA. Apr 16 2014;311(15):1547-55. doi:10.1001/jama.2014.3266
10. Harper DE, Schrepf A, Clauw DJ. Pain Mechanisms and Centralized Pain in Temporomandibular Disorders. J Dent Res. Sep 2016;95(10):1102-8. doi:10.1177/0022034516657070
11. Dydyk AM, Munakomi S. Thalamic Pain Syndrome. StatPearls. 2023.
12. Farhad K, Oaklander AL. Fibromyalgia and small-fiber polyneuropathy: What's in a name? Muscle Nerve. Nov 2018;58(5):611-613. doi:10.1002/mus.26179
13. Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. Oct 2010;33(10):2285-93. doi:10.2337/dc10-1303
14. Raasing LRM, Vogels OJM, Veltkamp M, van Swol CFP, Grutters JC. Current View of Diagnosing Small Fiber Neuropathy. J Neuromuscul Dis. 2021;8(2):185-207. doi:10.3233/JND-200490
15. Iyengar S, Johnson KW, Ossipov MH, Aurora SK. CGRP and the Trigeminal System in Migraine. Headache. May 2019;59(5):659-681. doi:10.1111/head.13529
16. Edvinsson JCA, Vigano A, Alekseeva A, et al. The fifth cranial nerve in headaches. J Headache Pain. Jun 5 2020;21(1):65. doi:10.1186/s10194-020-01134-1
17. Messlinger K, Fischer MJ, Lennerz JK. Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine. Keio J Med. 2011;60(3):82-9. doi:10.2302/kjm.60.82
18. Terrier LM, Fontaine D. Intracranial nociception. Rev Neurol (Paris). Sep 2021;177(7):765-772. doi:10.1016/j.neurol.2021.07.012
19. Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. Feb 5 2014;348:f7656. doi:10.1136/bmj.f7656
20. Wig R, Oakley CB. Dysautonomia and Headache in the Pediatric Population. Headache. Oct 2019;59(9):1582-1588. doi:10.1111/head.13659
21. Haensch CA, Tosch M, Katona I, Weis J, Isenmann S. Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome. Muscle Nerve. Dec 2014;50(6):956-61. doi:10.1002/mus.24245
22. Lacomis D. Small-fiber neuropathy. Muscle Nerve. Aug 2002;26(2):173-88. doi:10.1002/mus.10181
23. Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. Aug 2010;17(8):1010-8. doi:10.1111/j.1468-1331.2010.02969.x
24. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. Jan 2018;38(1):1-211. doi:10.1177/0333102417738202
25. Goldstein DS, Cheshire WP, Jr. The autonomic medical history. Clin Auton Res. Aug 2017;27(4):223-233. doi:10.1007/s10286-017-0425-7
26. Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. Nov 2013;154(11):2310-6. doi:10.1016/j.pain.2013.06.001
27. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. Jul 2010;17(7):903-12, e44-9. doi:10.1111/j.1468-1331.2010.03023.x
28. McCorquodale D, Smith AG. Clinical electrophysiology of axonal polyneuropathies. Handb Clin Neurol. 2019;161:217-240. doi:10.1016/b978-0-444-64142-7.00051-5
29. Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol. 2013;115:115-36. doi:10.1016/B978-0-444-52902-2.00007-2
30. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. Apr 2014;155(4):654-662. doi:10.1016/j.pain.2013.11.013
31. Blyth FM. Global burden of neuropathic pain. Pain. Mar 2018;159(3):614-617. doi:10.1097/j.pain.0000000000001127
32. Themistocleous AC, Ramirez JD, Shillo PR, et al. The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy. Pain. May 2016;157(5):1132-1145. doi:10.1097/j.pain.0000000000000491
33. Walk D. Role of skin biopsy in the diagnosis of peripheral neuropathic pain. Curr Pain Headache Rep. Jun 2009;13(3):191-6. doi:10.1007/s11916-009-0033-x
34. Gylfadottir SS, Christensen DH, Nicolaisen SK, et al. Diabetic polyneuropathy and pain, prevalence, and patient characteristics: a cross-sectional questionnaire study of 5,514 patients with recently diagnosed type 2 diabetes. Pain. Mar 2020;161(3):574-583. doi:10.1097/j.pain.0000000000001744
35. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. Jun 2008;136(3):380-387. doi:10.1016/j.pain.2007.08.013
36. Leung A. Addressing chronic persistent headaches after MTBI as a neuropathic pain state. J Headache Pain. Jun 19 2020;21(1):77. doi:10.1186/s10194-020-01133-2
37. Ashina S, Bendtsen L, Lyngberg AC, Lipton RB, Hajiyeva N, Jensen R. Prevalence of neck pain in migraine and tension-type headache: a population study. Cephalalgia. Mar 2015;35(3):211-9. doi:10.1177/0333102414535110
38. Barmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management. Curr Neurol Neurosci Rep. Mar 19 2019;19(5):20. doi:10.1007/s11910-019-0937-8
39. Vincent MB. Headache and neck. Curr Pain Headache Rep. Aug 2011;15(4):324-31. doi:10.1007/s11916-011-0195-1
40. Iser C, Arca K. Headache and Autonomic Dysfunction: a Review. Curr Neurol Neurosci Rep. Oct 2022;22(10):625-634. doi:10.1007/s11910-022-01225-3
41. Waliszewska-Prosol M, Straburzynski M, Czapinska-Ciepiela EK, Nowaczewska M, Gryglas-Dworak A, Budrewicz S. Migraine symptoms, healthcare resources utilization and disease burden in a large Polish migraine cohort : Results from 'Migraine in Poland'-a nationwide cross-sectional survey. J Headache Pain. Apr 11 2023;24(1):40. doi:10.1186/s10194-023-01575-4
42. Dodick DW. A Phase-by-Phase Review of Migraine Pathophysiology. Headache. May 2018;58 Suppl 1:4-16. doi:10.1111/head.13300
43. Barizien N, Le Guen M, Russel S, Touche P, Huang F, Vallee A. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep. Jul 7 2021;11(1):14042. doi:10.1038/s41598-021-93546-5
44. Gazerani P, Cairns BE. Dysautonomia in the pathogenesis of migraine. Expert Rev Neurother. Feb 2018;18(2):153-165. doi:10.1080/14737175.2018.1414601
45. Myers MI, Peltier AC. Uses of skin biopsy for sensory and autonomic nerve assessment. Curr Neurol Neurosci Rep. Jan 2013;13(1):323. doi:10.1007/s11910-012-0323-2
46. Johnson SA, Shouman K, Shelly S, et al. Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability. Neurology. Nov 30 2021;97(22):e2236-e2247. doi:10.1212/WNL.0000000000012894
47. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. Mar 2011;152(3 Suppl):S2-S15. doi:10.1016/j.pain.2010.09.030
48. Packard RC. The relationship of neck injury and post-traumatic headache. Curr Pain Headache Rep. Aug 2002;6(4):301-7. doi:10.1007/s11916-002-0051-4
49. Chen G, Zhang YQ, Qadri YJ, Serhan CN, Ji RR. Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain. Neuron. Dec 19 2018;100(6):1292-1311. doi:10.1016/j.neuron.2018.11.009
50. Sommer C, Leinders M, Uceyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. Mar 2018;159(3):595-602. doi:10.1097/j.pain.0000000000001122