*Article* **Serum Concentrations of the Endocannabinoid, 2-Arachidonoylglycerol, in the Peri-Trauma Period Are Positively Associated with Chronic Pain Months Later**

**Colleen M. Trevino 1,\*, Cecilia J. Hillard 2, Aniko Szabo 3 and Terri A. deRoon-Cassini 1,4**


**Abstract:** Endocannabinoid signaling and the hypothalamic-pituitary-adrenal axis are activated by trauma and both stress systems regulate the transition from acute to chronic pain. This study aimed to develop a model of relationships among circulating concentrations of cortisol and endocannabinoids (eCBs) immediately after traumatic injury and the presence of chronic pain months later. Pain scores and serum concentrations of eCBs and cortisol were measured during hospitalization and 5–10 months later in 147 traumatically injured individuals. Exploratory correlational analyses and path analysis were completed. The study sample was 50% Black and Latino and primarily male (69%); 34% percent endorsed a pain score of 4 or greater at follow-up and were considered to have chronic pain. Path analysis was used to model relationships among eCB, 2-arachidonolyglycerol (2-AG), cortisol, and pain, adjusting for sex and injury severity (ISS). Serum 2-AG concentrations at the time of injury were associated with chronic pain in 3 ways: a highly significant, independent positive predictor; a mediator of the effect of ISS, and through a positive relationship with cortisol concentrations. These data indicate that 2-AG concentrations at the time of an injury are positively associated with chronic pain and sugges<sup>t</sup> excessive activation of endocannabinoid signaling contributes to risk for chronic pain.

**Keywords:** *N*-arachidonoylethanolamine; cortisol; chronic pain; injury
