Chronic Pain Associated With Traumatic Brain Injury: Causes and Management

Any trauma that causes jarring acceleration or deceleration of the brain within the skull can lead to brain dysfunction consistent with traumatic brain injury (TBI).¹ The force might be direct, such as a violent blow to the head or a fall in which the head strikes the ground, or indirect like the shockwave from an explosion.² Gunshots, knife wounds, or other penetrating injuries to the brain also cause TBI.

Approximately 1.5 million Americans experience TBI each year, and the related economic burden is estimated at $86 billion annually.³ Although more than three-quarters of TBI cases are mild with rapid symptom resolution, some people suffer persistent debilitation and pain.⁴ Karen-Amanda Irvine, PhD, a research associate at the Veterans Affairs (VA) Palo Alto Health Care System in California, and colleagues have been studying the relationship between pain and TBI. Acute pain due to tissue damage is common and typically resolves after several weeks, once the brain has healed, however, chronic pain (ie, ongoing pain lasting for at least 3 to 6 months) may arise after TBI.⁴ “Accumulating evidence suggests that chronic pain is common after TBI,” Dr Irvine told Clinical Pain Advisor. It is unclear whether pain after TBI is attributable primarily to the brain injury, to injuries suffered concurrently with the brain injury, or to psychological factors.¹ “As yet, our understanding of the causes and consequences of pain after TBI is limited despite TBI being very common,” she added.

Prevalence of Chronic Pain After Traumatic Brain Injury

Estimates of the prevalence of chronic pain in patients with TBI vary between studies, and Dr Irvine noted, “It is difficult to say without further research exactly how likely it is that a patient will experience pain after TBI.” She said most of the literature on chronic pain after TBI focuses on the prevalence of headache, which is the most common site of pain in patients who have experienced TBI. A 2008 systematic review was conducted to determine the prevalence of chronic headache and chronic pain in civilians and combat veterans after TBI.⁵ Of the 3289 civilians with TBI, 51.5% (95% CI, 49.8-53.2%) had chronic pain.⁵ Of the 20 studies included in this review, 12 evaluated chronic headache (n=1670), which affected 57.8% (95% CI, 55.5%-60.2%) of civilians. Analyses of 3 studies of combat veterans with TBI (n=917) indicated that 43.1% (95% CI, 39.9-46.3%) experienced chronic pain, and 35.9% (95% CI, 32.8%-39.0%) had chronic headache. In a recent study, the records of 116,913 combat veterans who completed a Comprehensive Traumatic Brain Injury Evaluation with the VA due to suspected TBI were reviewed.⁶ Overall, 57% of the veterans had received at least 1 diagnosis of chronic pain and 73% reported moderate to severe pain disability.

The 2008 review analyzed the prevalence of chronic pain in civilians with mild (10 studies; n=1046) or severe TBI (9 studies; n=1063).⁵ Chronic pain was experienced by 75.3% (95% CI, 72.7%-77.9%) of patients with mild TBI vs 32.1% (95% CI, 29.3%-34.9%) of patients with severe TBI.⁵ “This is surprising but not impossible, as the assessment of a lower rate of pain in more severely injured patients may be due to difficulties in assessing their pain because of an altered level of consciousness, cognitive impairments, or verbal difficulties,” Dr Irvine said. The 2017 study in combat veterans indicated lower rates of chronic pain associated with mild TBI vs moderate to severe TBI (58.8% vs 64.4%).⁶ In another study, the reported prevalence of posttraumatic headache was found to range from 47% to 95% after mild TBI, and from 33% to 38% after moderate to severe TBI.¹ Other studies have indicated a higher prevalence of posttraumatic headache in patients with moderate to severe TBI than in patients with mild TBI.⁴ 

Onset of Chronic Pain After Traumatic Brain Injury

For approximately 54% to 71% of patients, posttraumatic headache occurs shortly after TBI, with 70% of patients with mild TBI reporting headaches 6 months after injury, and 40% experiencing headaches for a year or longer. ^1,4 In the most severe, persistent cases, the headaches are similar to migraines.⁸ Patients may also experience tension headaches, or a combination of migraine and tension headaches.⁴ Female gender, prior headache disorder, and a family history of headache disorder were found to be associated with an increased risk for developing posttraumatic headache.⁸

According to Dr Irvine, “The most common sites of pain [other than the head] are the neck, back, shoulders, and extremities, and TBI-associated pain has been characterized as primarily musculoskeletal.” In some instances, chronic pain may result from injuries suffered at the same time as TBI. Between 10% and 20% of patients develop neurogenic heterotopic ossification after TBI, in which mature lamellar bone forms within soft tisse.⁷ The condition typically arises 2 to 4 months after TBI and causes severe musculoskeletal pain.⁷ Less common pain syndromes — primarily occurring in patients with severe TBI — include peripheral neuropathy, complex regional pain syndrome, and neuromuscular spasticity.^4,5 Late-onset pain syndromes have also been reported, with symptoms arising 6 months or longer after the brain injury.⁴ “If a patient with TBI has been diagnosed with chronic pain, it is difficult to estimate how long they may experience it and whether it will resolve,” noted Dr Irvine.

Causes of Chronic Pain After Traumatic Brain Injury

Researchers have proposed several complex mechanisms to explain the association between chronic pain and TBI. “Both clinical investigations and animal studies have suggested that dysfunction in the brain and spinal cord contribute to chronic pain after TBI,” said Dr Irvine. “Specifically, descending neural connections from the brain to the spinal cord, which normally inhibit pain circuits, become dysfunctional after TBI and contribute to pain,” she added. Additional research is needed to confirm the role of the descending pain-control pathway and to determine “whether the degree of its dysfunction dictates the severity of TBI-associated pain.”

Neuroinflammation and neurodegeneration, which play a role in neurodegenerative diseases like Parkinson and Alzheimer’s disease, are other possible contributors to the emergence of chronic pain after TBI.⁴ The evidence linking neuroinflammation to chronic pain after TBI is less robust. Other proposed mechanisms are axonal damage secondary to rapid acceleration or deceleration of the head, synaptic changes, or epigenetic changes like DNA methylation and chromatin modification.⁴

Patients with post-traumatic stress disorder (PTSD), depression, or a history of psychiatric disorders appear more likely to experience chronic pain and to report pain-related disability after TBI.^1,6 PTSD was found to be the main driver of chronic pain — especially back and joint pain — in combat veterans after TBI.⁶ The researchers hypothesized that this relationship between PTSD and chronic pain may be due to the elevation of adrenergic hormones and other biochemicals after TBI, which contribute to increasing muscle tension and to heightening pain perception.⁶ Other possible mechanisms underlying this association include the increase in pain catastrophizing often observed in individuals with PTSD, and the upregulation of the dopamine pathway involved in pain perception and psychological distress.^1,6

Management

Early diagnosis and management of pain and psychological distress in patients with TBI may reduce their risk for developing a chronic pain condition.¹ Early recognition of TBI-related pain is complicated by the fact that mild TBI often remains undiagnosed.^1,4 In patients with a diagnosis of mild TBI, education related to expectations and symptom management, in addition to how to manage symptoms, follow-up visits recommendations may be useful.¹

According to Dr Irvine, Clinical Practice Guidelines formulated by the VA and US Department of Defense address treatment of posttraumatic headache in patients with TBI and recommend treatment using standard measures based on headache subtype.⁴ However, there are no evidence-based guidelines on effective management of other types of chronic pain in TBI.⁴ Chronic pain in patients with TBI is highly heterogeneous, and clinicians must use their discretion in managing each patient’s symptoms.¹ A multi-disciplinary approach may be required that combines pharmacologic options and psychological interventions to improve coping mechanisms.¹

Follow @ClinicalPainAdv

References

1. Khoury S, Benavides R. Pain with traumatic brain injury and psychological disorders [published online Jun 13, 2017]. Prog Neuropsychopharmacol Biol Psychiatry.  doi:10.1016/j.pnpbp.2017.06.007
2. American Association of Neurological Surgeons. Traumatic brain injury. www.aans.org/Patients/Neurosurgical-Conditions-and-Treatments/Traumatic-Brain-Injury. 2017. Accessed October 19, 2017.
3. Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: a summary report and call to action. Ann Neurol. 2017;81:479-484.
4. Irvine KA, Clark JD. Chronic pain after traumatic brain injury: pathophysiology and pain mechanisms [published online August 29, 2017]. Pain Med. https://doi.org/10.1093/pm/pnx153
5. Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury. JAMA. 2008;300(6):771-719.
6. Seal KH, Bertenthal D, Barnes DE, et al. Association of traumatic brain injury with chronic pain in Iraq and Afghanistan veterans: effect of comorbid mental health conditions. Arch Phys Med Rehabil. 2017;98(8):1636-1645.
7. Reznik JE, Brios E, Milanese S, et al. Prevalence of neurogenic heterotopic ossification in traumatic head- and spinal-injured patients admitted to a tertiary referral hospital in Australia. Health Care Manag (Frederick). 2015;34(1):54-61.
8. Moya LS, Pradhan AA. From blast to bench: a translational mini-review of posttraumatic headache. J Neurosci Res. 2017;95(6):1347-1354.