Pain after traumatic brain injury (TBI) fosters hemorrhage at the site of injury.

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. In many cases, TBI is accompanied by additional tissue damage (polytrauma) that will engage pain (nociceptive) sensory fibers. Prior work using an animal model (rats) has shown that nociceptive stimulation after a spinal cord injury (SCI) fosters hemorrhage at the site of injury and amplifies secondary tissue loss. The current study explores whether noxious stimulation fosters hemorrhage after a TBI. Anesthetized rats were given a cortical impact of the frontal region. Nociceptive fibers that express the transient receptor potential vanilloid 1 (TRPV1) receptor were engaged by applying capsaicin to one hind paw a day after injury. Brain tissue was collected three hours later. Capsaicin applied contralateral, but not ipsilateral, to injury increased the area of hemorrhage in both male and female animals. Noxious stimulation fostered capillary fragmentation in the area of injury and increased infiltration of Evan's blue, implying a breakdown of the blood-brain barrier. Inducing a coma-like state with pentobarbital blocked capsaicin-induced hemorrhage after TBI. Systemic morphine also had a protective effect. Engaging pain fibers with electrical stimulation applied to the tail increased the area of hemorrhage and this effect too was blocked by systemic morphine. The results suggest that pain after TBI fosters hemorrhage, which increases the area of secondary tissue loss.