In this review, we discuss the comorbidity of traumatic brain injury (TBI) and pain among civilians and military members, the common causes of pain resulting from TBI, and offer insight about the therapeutic management of TBI symptoms and pain. Traumatic brain injury (TBI) is a debilitating health problem and one of the most common post-TBI symptoms is pain, which can contribute to psychological issues such as Post-traumatic stress disorder (PTSD) and depression. Headache pain appears to be the most common type of pain that results from TBI, yet pain can also be more widespread. Managing TBI symptoms and pain simultaneously is difficult because extensive randomized control and clinical studies assessing the effectiveness of therapeutic approaches are lacking. Pharmacological agents such as antidepressants and Triptans and nonpharmacological therapies such as cognitive rehabilitation and physical therapies are commonly used yet it is unknown how effective these therapies are in the long-term. A combination of pharmacological and non-pharmacological therapies is often more effective for managing TBI symptoms and pain than either treatment alone. However, future research is needed to determine the most therapeutic approaches for managing the comorbidity of pain and TBI symptoms in the long term. This review offers suggestions for such future studies.

The ventrolateral periaqueductal gray (vlPAG) contributes to morphine antinociception and tolerance. Chronic inflammatory pain causes changes within the PAG that are expected to enhance morphine tolerance. This hypothesis was tested by assessing antinociception and tolerance following repeated microinjections of morphine into the vlPAG of rats with chronic inflammatory pain. Microinjection of morphine into the vlPAG reversed the allodynia caused by intraplantar administration of Complete Freund's Adjuvant (CFA), and produced antinociception on the hot plate test. Although there was a gradual decrease in morphine antinociception with repeated testing, there was no evidence of tolerance when morphine and saline treated rats with hind paw inflammation were tested with cumulative doses of morphine. In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance. The lack of tolerance in CFA treated rats was evident whether rats were exposed to repeated behavioral testing or not (Experiment 2) and whether they were treated with 4 or 8 prior microinjections of morphine into the vlPAG (Experiment 3). These data demonstrate that chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does disrupt the development of tolerance.

Our analysis implicates that headache is a common and acutely persistent symptom in mTBI regardless of injury context. Additionally, patients in mounted vs dismounted injury did not report significant differences in symptom prevalence. Although knowing the injury context (i.e., dismounted vs mounted) may be beneficial for providers to understand symptom presentations and deliver accurate anticipatory guidance for patients with blast-related mTBI, no significant differences were observed in this population. This may be due to the population characteristic as the trajectory of recovery may vary for patients who were not able to return to full duty within 30 d or required higher levels of care.

Traumatic brain injury (TBI) is one of the most common forms of neurotrauma that has affected more than 250,000 military service members over the last decade alone. While in battle, service members who experience TBI are at significant risk for the development of normal TBI symptoms, as well as risk for the development of psychological disorders such as Post-Traumatic Stress Disorder (PTSD). As such, these service members often require intense bouts of medication and therapy in order to resume full return-to-duty status. The primary aim of this study is to identify the relationship between the administration of specific medications and reductions in symptomology such as headaches, dizziness, or light-headedness. Service members diagnosed with mTBI and seen at the Concussion Restoration Care Center (CRCC) in Afghanistan were analyzed according to prescribed medications and symptomology. Here, we demonstrate that in such situations with sparse labels and small feature sets, classic analytic techniques such as logistic regression, support vector machines, naïve Bayes, random forest, decision trees, and k-nearest neighbor are not well suited for the prediction of outcomes. We attribute our findings to several issues inherent to this problem setting and discuss several advantages of spectral graph methods.

Background: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms. Purpose: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response. Methods: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes -- natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) -- to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes. Results: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms. Conclusion: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.