Novel Intervention for TBI-induced Opioid Seeking

Of the more than 300,000 service personnel that have sustained traumatic brain injury (TBI) due to recent conflicts, 70-80% are treated with opioids for post-injury symptoms. TBI-injured Veterans clinically managed for these symptoms that include chronic pain, are more likely to receive opioid-based treatment and engage in higher-risk opioid use. This increase in prescription opioid use among Veterans with TBI reflects the nationwide opioid abuse and dependence crisis and highlights the need to develop non-opioid based treatment for chronic symptom management. Recent data indicate early activation of oxidative stress mediators and long-term response of pro-inflammatory factors are common to both opioid action and TBI and that targeting of these mechanisms, particularly during the sustained inflammatory response, would be an effective approach to mitigate opioid addiction vulnerability in TBI-affected Veterans. An emerging and promising approach is use of photobiomodulation (PBM), a low level light therapy known to attenuate both oxidative stress and inflammatory signaling in clinical and experimental applications. While successful in reversing TBI-induced cognitive deficits, PBM will be used in the current proposal as a novel means of addressing exacerbated opioid seeking that occurs after injury. Our preliminary data support use of PBM to mitigate TBI-induced elevations in reactive oxygen species, inflammatory markers and morphine seeking, which we also demonstrate to be attenuated following pharmacological treatment with antioxidants and anti-inflammatory drugs. The central hypothesis is that TBI will enhance chronic morphine seeking through exacerbated recruitment of oxidative and proinflammatory systems in regions responsible for these behaviors, and that these will be reversed by neurotherapeutic intervention with PBM. This hypothesis will be tested with two Specific Aims: (1) Quantify the effect PBM on TBI-induced oxidative and inflammatory markers in reward- and pain-related regions [and blood] in the chronic post-injury period, [(2) Quantify the effect of PBM, and adjunctive exposure to antioxidant or anti-inflammatory compounds, on morphine-seeking behavior.] This work would establish that PBM therapy attenuates injury-induced oxidative and inflammatory outcomes that may drive aberrant pain and opioid seeking in the chronic post-injury period. Identification of non-invasive alternatives to opioid-based strategies for chronic symptom relief would provide an improved strategic framework to assist Veterans in the post-TBI rehabilitative period.