1. 2025;28;231-240Pain Management in Mild Traumatic Brain Injury: Central Sensitization as a Multispecialty Challenge
   Retrospective Observation
   Christopher File, BSA, Remi Nader, MD, Alejandro Villasante-Tezanos, PhD, Rowaid Ahmed, MD, Sean Pappolla, ., Fauwad Ahmed, MD, Ernesto G. Miranda-Morales, PhD, Yingxin Zhao, PhD, Xiang Fang, MD, PhD, Alan D. Kaye, MD, PhD, and Miguel A. Pappolla, MD, PhD.

BACKGROUND: Several studies indicate that approximately two-thirds of individuals with mild traumatic brain injury (mTBI) will develop chronic pain, which is often debilitating and a primary factor in long-term disability. Patients with mTBI can suffer concurrently from multiple pain types, such as chronic neuropathic (central or peripheral), nociceptive, or nociplastic pain; however, the prevailing pain types in mTBI patients remain undetermined. This knowledge void limits the formulation of effective therapies for mTBI-related pain.

OBJECTIVE: We aimed to identify the predominant pain mechanism in patients who had developed persistent post-concussive syndrome (PPCS) after the onset of their mTBI.

STUDY DESIGN: We conducted a retrospective observational study following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Our study focused on a cohort of mTBI patients with PPCS and chronic pain.

SETTING: This study was conducted at an outpatient neurology clinic from January 2020 to December 2023.

METHODS: The study included patients who met the criteria for post-mTBI PPCS. Exclusion criteria consisted of a history of chronic pain before the injury, being in the acute/subacute stage (fewer than 90 days after receiving the injury), or the presence of any other neurological comorbidities. We employed a range of diagnostic instruments, including a clinical research tool to measure the degree of central sensitization. Since patients with mTBI often show normal structural imaging, we used several neurophysiological techniques, including evoked potentials, videonystagmography, and quantitative electroencephalography, to confirm the presence of brain pathology objectively. The severity of the post-concussive symptoms was measured using the Rivermead Post-Concussion Symptoms Questionnaire. Central sensitization was assessed using the Widespread Pain Index and the Symptom Severity Index. The correlation between concussion severity and widespread pain was analyzed statistically.

RESULTS: Out of 223 initial mTBI patients, 67 met the study criteria. The main reasons for exclusions included pre-existing chronic pain or other neurological diagnoses. Among the patients, 39 (58%) were male, averaging 45.7 years of age (range: 20-72). Ethnicity distribution was as follows: 26 (39%) Hispanic, 22 (33%) White, 12 (18%) Black or African American, and 7 (10%) Asian or Pacific Islander. We found that patients with PPCS exhibited high levels of central sensitization, highlighting its critical role in the pathophysiology of chronic pain post-mTBI. We observed a significant correlation between the extent of central sensitization and the presence of non-painful symptoms, suggesting shared neuropathological processes between chronic pain and other PPCS manifestations.

LIMITATIONS: This project was a retrospective study, which made it subject to limitations. Also, the measures used to assess some variables were self-reported, subjecting the data to recall bias.

CONCLUSION: We showed that high levels of central sensitization were universally present in the cohort studied and should be considered the primary therapeutic target in managing chronic post-mTBI pain. Therefore, chronic pain in this population is likely driven by central nervous system pathology that contributes to both the pain experience and other post-concussive symptomatology. A significant clinical implication of our study is that patients displaying high levels of central sensitization often report severe pain in discrete body parts, leading clinicians to mistakenly focus on treating the issue with antinociceptive therapies or interventional procedures that are frequently ineffective.

KEY WORDS: Mild traumatic brain injury, concussion, chronic pain, central sensitization, nociplastic pain, persistent post-concussion syndrome, fibromyalgia, pain management