Distinct persistent post-traumatic headache symptoms and quantitative sensory testing profiles may be linked to different etiologies, potentially involving various levels of neuropathic and inflammatory pain, and if confirmed in a larger cohort, could be used to further characterize and differentiate between persistent post-traumatic headache subgroups in studies aimed to improve treatment.

Persistent post-traumatic headache subjects with migraine-like symptoms reported that bright light and focused attention aggravated their pain, while stress and nervousness were reported to aggravate the headache in subjects with tension-type headache-like symptoms. Quietness was better in alleviating migraine-like persistent post-traumatic headache, while anti-inflammatory medications provided better relief in tension-type headache-like persistent post-traumatic headache. The two persistent post-traumatic headache subgroups exhibited distinct quantitative sensory testing profiles with subjects exhibiting tension-type headache-like persistent post-traumatic headache displaying a more pronounced cephalic and extracephalic thermal hypoalgesia that was accompanied by cephalic mechanical hyperalgesia. While both persistent post-traumatic headache subgroups had high levels of post-traumatic stress disorder, there was a positive correlation with pain severity in subjects with tension-type headache-like symptoms, but a negative correlation in subjects with migraine-like symptoms.

We compared clinical features and quantitative sensory testing profiles between two distinct cohorts of persistent post-traumatic headache subjects that exhibited symptoms resembling either migraine (n = 15) or tension-type headache (n = 13), as well as to headache-free subjects that had suffered traumatic brain injury (n = 19), and to healthy controls (n = 10). We aimed to determine whether the two persistent post-traumatic headache subgroups could be discriminated based on additional clinical features, distinct quantitative sensory testing profiles, or the interaction of pain severity with the level of post-traumatic stress disorder.

Persistent post-traumatic headache remains a poorly understood clinical entity. Although there are currently no accepted therapies for persistent post-traumatic headache, its clinical symptoms, which primarily resemble those of migraine or tension-type headache, often serve to guide treatment. However, evidence-based justification for this treatment approach remains lacking given the paucity of knowledge regarding the characteristics of these two major persistent post-traumatic headache phenotypes and their etiology.

References

1. Vargas, BB, Dodick, DW. Posttraumatic headache . Curr Opin Neurol 2012 ; 25: 284 – 289 .

Google Scholar Crossref | Medline

2. Kamins, J, Charles, A. Posttraumatic headache: Basic mechanisms and therapeutic targets . Headache 2018 ; 58: 811 – 826 .

Google Scholar Crossref | Medline

3. Hoffman, JM, Lucas, S, Dikmen, S, et al. Natural history of headache after traumatic brain injury . J Neurotrauma 2011 ; 28: 1719 – 1725 .

Google Scholar Crossref | Medline | ISI

4. Lucas, S, Hoffman, JM, Bell, KR, et al. A prospective study of prevalence and characterization of headache following mild traumatic brain injury . Cephalalgia 2014 ; 34: 93 – 102 .

Google Scholar SAGE Journals | ISI

5. Kjeldgaard, D, Forchhammer, H, Teasdale, T, et al. Chronic post-traumatic headache after mild head injury: A descriptive study . Cephalalgia 2014 ; 34: 191 – 200 .

Google Scholar SAGE Journals | ISI

6. Romesser, J, Booth, J, Benge, J, et al. Mild traumatic brain injury and pain in Operation Iraqi Freedom/Operation Enduring Freedom veterans . J Rehabil Res Dev 2012 ; 49: 1127 – 1136 .

Google Scholar Crossref | Medline

7. Watanabe, TK, Bell, KR, Walker, WC, et al. Systematic review of interventions for post-traumatic headache . PM&R 2012 ; 4: 129 – 140 .

Google Scholar Crossref

8. Lucas, S, Ahn, AH. Posttraumatic headache: Classification by symptom-based clinical profiles . Headache 2018 ; 58: 873 – 882 .

Google Scholar Crossref | Medline

9. Howard, L, Dumkrieger, G, Chong, CD, et al. Symptoms of autonomic dysfunction among those with persistent posttraumatic headache attributed to mild traumatic brain injury: A comparison to migraine and healthy controls . Headache 2018 ; 58: 1397 – 1407 .

Google Scholar Crossref | Medline

10. Cruz-Almeida, Y, Fillingim, RB. Can quantitative sensory testing move us closer to mechanism-based pain management? . Pain Med 2014 ; 15: 61 – 72 .

Google Scholar Crossref | Medline | ISI

11. Clark, J, Nijs, J, Yeowell, G, et al. What are the predictors of altered central pain modulation in chronic musculoskeletal pain populations? A systematic review . Pain Phys 2017 ; 20: 487 – 500 .

Google Scholar Medline

12. Defrin, R, Gruener, H, Schreiber, S, et al. Quantitative somatosensory testing of subjects with chronic post-traumatic headache: Implications on its mechanisms . Eur J Pain 2010 ; 14: 924 – 931 .

Google Scholar Crossref | Medline | ISI

13. Defrin, R, Riabinin, M, Feingold, Y, et al. Deficient pain modulatory systems in patients with mild traumatic brain and chronic post-traumatic headache: Implications for its mechanism . J Neurotrauma 2015 ; 32: 28 – 37 .

Google Scholar Crossref | Medline | ISI

14. Spani, CB, Braun, DJ, Van Eldik, LJ. Sex-related responses after traumatic brain injury: Considerations for preclinical modeling . Front Neuroendocrinol 2018 ; 50: 52 – 66 .

Google Scholar Crossref | Medline

15. Headache Classification Committee of the International Headache Society . The International Classification of Headache Disorders, 3rd edition (beta version) . Cephalalgia 2013 ; 33: 629 – 808 .

Google Scholar SAGE Journals | ISI

16. Zeilig, G, Enosh, S, Rubin-Asher, D, et al. The nature and course of sensory changes following spinal cord injury: Predictive properties and implications on the mechanism of central pain . Brain 2012 ; 135: 418 – 430 .

Google Scholar Crossref | Medline

17. Antonaci, F, Sand, T, Lucas, GA. Pressure algometry in healthy subjects: Inter-examiner variability . Scand J Rehabil Med 1998 ; 30: 3 – 8 .

Google Scholar Crossref | Medline

18. Kosek, E, Ekholm, J, Hansson, P. Pressure pain thresholds in different tissues in one body region. The influence of skin sensitivity in pressure algometry . Scand J Rehabil Med 1999 ; 31: 89 – 93 .

Google Scholar Crossref | Medline

19. Defrin, R, Ronat, A, Ravid, A, et al. Spatial summation of pressure pain: Effect of body region . Pain 2003 ; 106: 471 – 480 .

Google Scholar Crossref | Medline

20. Stiasny-Kolster, K, Magerl, W, Oertel, WH, et al. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome . Brain 2004 ; 127: 773 – 782 .

Google Scholar Crossref | Medline

21. Zeilig, G, Rivel, M, Weingarden, H, et al. Evidence of a neuropathic origin in hemiplegic shoulder pain . Pain 2013 ; 154: 959 – 960 .

Google Scholar Crossref | Medline

22. Jennett, B, Teasdale, G, Braakman, R, et al. Predicting outcome in individual patients after severe head injury . Lancet 1976 ; 1: 1031 – 1034 .

Google Scholar Crossref | Medline | ISI

23. Melzack, R . The McGill Pain Questionnaire: Major properties and scoring methods . Pain 1975 ; 1: 277 – 299 .

Google Scholar Crossref | Medline | ISI

24. Slotty, PJ, Bara, G, Kowatz, L, et al. Occipital nerve stimulation for chronic migraine: A randomized trial on subthreshold stimulation . Cephalalgia 2015 ; 35: 73 – 78 .

Google Scholar SAGE Journals | ISI

25. Cappon, D, Ryterska, A, Lagrata, S, et al. Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life . Cephalalgia 2019 ; 39: 1099 – 1110 .

Google Scholar SAGE Journals | ISI

26. Bryant, RA, Marosszeky, JE, Crooks, J, et al. Interaction of posttraumatic stress disorder and chronic pain following traumatic brain injury . J Head Trauma Rehab 1999 ; 14: 588 – 594 .

Google Scholar Crossref | Medline | ISI

27. Solomon, Z, Benbenishty, R, Neria, Y, et al. Assessment of PTSD: Validation of the revised PTSD Inventory . Isr J Psychiatry Relat Sci 1993 ; 30: 110 – 115 .

Google Scholar Medline | ISI

28. Benjamini, Y, Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing . J Royal Stat Soc Series B 1995 ; 57: 289 – 300 .

Google Scholar

29. Starling AJ, Jarvis N and Schwedt TJ. Cutaneous heat pain and light-induced pain thresholds in posttraumatic headache attributed to mild traumatic brain injury. In: Proceedings of 61st Annual Scientific Meeting American Headache Society, Philadelphia, PA, 2019, p.17.

Google Scholar

30. Cathcart, S, Winefield, AH, Lushington, K, et al. Stress and tension-type headache mechanisms . Cephalalgia 2010 ; 30: 1250 – 1267 .

Google Scholar SAGE Journals | ISI

31. Noseda, R, Copenhagen, D, Burstein, R. Current understanding of photophobia, visual networks and headaches . Cephalalgia 2019 ; 39: 1623 – 1634 .

Google Scholar SAGE Journals | ISI

32. Kelman, L . Migraine pain location: A tertiary care study of 1283 migraineurs . Headache 2005 ; 45: 1038 – 1047 .

Google Scholar Crossref | Medline | ISI

33. Becker, WJ . Acute migraine treatment in adults . Headache 2015 ; 55: 778 – 793 .

Google Scholar Crossref | Medline | ISI

34. Castien, RF, van der Wouden, JC, De Hertogh, W. Pressure pain thresholds over the cranio-cervical region in headache: A systematic review and meta-analysis . J Headache Pain 2018 ; 19: 9 .

Google Scholar Crossref | Medline

35. Langemark, M, Jensen, K, Jensen, TS, et al. Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache . Pain 1989 ; 38: 203 – 210 .

Google Scholar Crossref | Medline | ISI

36. Jensen, R, Bendtsen, L, Olesen, J. Muscular factors are of importance in tension-type headache . Headache 1998 ; 38: 10 – 17 .

Google Scholar Crossref | Medline | ISI

37. de Tommaso, M, Libro, G, Guido, M, et al. Heat pain thresholds and cerebral event-related potentials following painful CO 2 laser stimulation in chronic tension-type headache . Pain 2003 ; 104: 111 – 119 .

Google Scholar Crossref | Medline | ISI

38. Weissman-Fogel, I, Sprecher, E, Granovsky, Y, et al. Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: Clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons . Pain 2003 ; 104: 693 – 700 .

Google Scholar Crossref | Medline | ISI

39. Nahman-Averbuch, H, Shefi, T, Schneider, VJ, et al. Quantitative sensory testing in patients with migraine: A systematic review and meta-analysis . Pain 2018 ; 159: 1202 – 1223 .

Google Scholar Crossref | Medline

40. Schwedt, TJ, Chong, CD, Peplinski, J, et al. Persistent post-traumatic headache vs. migraine: An MRI study demonstrating differences in brain structure . J Headache Pain 2017 ; 18: 87 .

Google Scholar Crossref | Medline

41. Dumkrieger, G, Chong, CD, Ross, K, et al. Static and dynamic functional connectivity differences between migraine and persistent post-traumatic headache: A resting-state magnetic resonance imaging study . Cephalalgia 2019 ; 39: 1366 – 1381 .

Google Scholar SAGE Journals | ISI

42. Chong, CD, Peplinski, J, Berisha, V, et al. Differences in fibertract profiles between patients with migraine and those with persistent post-traumatic headache . Cephalalgia 2019 ; 39: 1121 – 1133 .

Google Scholar SAGE Journals | ISI

43. Schwedt, TJ . Structural and functional brain alterations in post-traumatic headache attributed to mild traumatic brain injury: A narrative review . Front Neurol 2019 ; 10: 615 .

Google Scholar Crossref | Medline

44. Defrin, R, Ohry, A, Blumen, N, et al. Characterization of chronic pain and somatosensory function in spinal cord injury subjects . Pain 2001 ; 89: 253 – 263 .

Google Scholar Crossref | Medline | ISI

45. Finnerup, NB, Johannesen, IL, Fuglsang-Frederiksen, A, et al. Sensory function in spinal cord injury patients with and without central pain . Brain 2003 ; 126: 57 – 70 .

Google Scholar Crossref | Medline | ISI

46. Ofek, H, Defrin, R. The characteristics of chronic central pain after traumatic brain injury . Pain 2007 ; 131: 330 – 340 .

Google Scholar Crossref | Medline

47. Roper, LS, Nightingale, P, Su, Z, et al. Disability from posttraumatic headache is compounded by coexisting posttraumatic stress disorder . J Pain Res 2017 ; 10: 1991 – 1996 .

Google Scholar Crossref | Medline

48. Bomyea, J, Lang, AJ, Delano-Wood, L, et al. Neuropsychiatric predictors of post-injury headache after mild-moderate traumatic brain injury in veterans . Headache 2016 ; 56: 699 – 710 .

Google Scholar Crossref | Medline

49. Rosenthal, JF, Erickson, JC. Post-traumatic stress disorder in US soldiers with post-traumatic headache . Headache 2013 ; 53: 1564 – 1572 .

Google Scholar Crossref | Medline | ISI

50. Ravn, SL, Hartvigsen, J, Hansen, M, et al. Do post-traumatic pain and post-traumatic stress symptomatology mutually maintain each other? A systematic review of cross-lagged studies . Pain 2018 ; 159: 2159 – 2169 .

Google Scholar Crossref | Medline

51. Mickleborough, MJ, Daniels, JK, Coupland, NJ, et al. Effects of trauma-related cues on pain processing in posttraumatic stress disorder: An fMRI investigation . J Psychiatry Neurosci 2011 ; 36: 6 – 14 .

Google Scholar Crossref | Medline | ISI

52. Saunders, K, Merikangas, K, Low, NC, et al. Impact of comorbidity on headache-related disability . Neurology 2008 ; 70: 538 – 547 .

Google Scholar Crossref | Medline | ISI