Chronic pain and thalamic abnormalities after traumatic brain injury

Abstract

Traumatic brain injury (TBI) is an important public health issue in both military and civilian life. Many suffer from cognitive and motor deficits, as well as from excruciating, unrelenting chronic pain (TBI-Pain). TBI-Pain is associated with hypersensitivity to mild tactile and thermal stimulation of the face and scalp, a result of central sensitization, a process by which brain structures undergo maladaptive plasticity, resulting in abnormal activity of brain neurons. Recently central sensitization of the posterior thalamus (PO) has been implicated in chronic pain disorders, spinal cord injury and migraine. We therefore hypothesized that chronic pain after TBI is also associated with abnormal activity of the PO thalamus. Here, we tested this hypothesis using a novel model of blast-TBI with two unique features: (i) blast-TBI was performed in awake, unanesthetized rats, to simulate the human experience and to preclude anesthesia-induced dampening of post-injury increases in excitatory activity that is crucial for the development of central pain; (ii) only the cranium, rather than the entire body, was exposed to a collimated blast wave, with the blast wave striking the posterior cranium in the region of the occipital crest and foramen magnum. Testing for thermal hyperalgesia of the face (distal from direct injury) revealed that blast-TBI rats had a significantly lower tolerance to pain, compared to the control group. Consistent with the behavioral data, single unit electrophysiological recordings from PO showed an increase in the spontaneous and evoked firing rate of neurons from blast-TBI rats, compared to sham. These data support the hypothesis that blast-TBI is associated with hyperalgesia and maladaptive plasticity in the PO thalamus.