Abstract
Mild traumatic brain injury (mTBI) represents one of the major contributors to the overall global disability. Post-traumatic headache (PTH) is a frequent and often the most debilitating associated symptom. For some patients, headache resolves in the first weeks to 3 months following a mTBI, a condition defined as acute PTH (APTH). However, several individuals continue to experience ongoing or intermittent headaches that persist beyond 3 months, a condition defined as persistent PTH (PPTH). Many animal models of TBI have been developed. Often, these are performed by impacting the head of rodents whose motion is mechanically fixed and/or involves an open skull. The following protocol describes a model where the head is unfixed, allowing free linear and rotational forces induced by a standardized weight drop that has similarities to concussions that occur in many situations in humans. The headache in this model is characterized by initial transient tactile allodynia in the cephalic region that lasts for several days and reflects the pain-like feature of APTH. Tactile allodynia is also observed in the extra-cephalic body areas suggestive of central sensitization and PTH. Following resolution of the transient APTH, animals display long-lasting latent sensitization, where baseline pain responses are normal, but otherwise innocuous provocative stimuli provoke cephalic and hind paw tactile allodynia, suggesting the development of persistent sensitization that may underlie PPTH. The key advantages of this model include concussion-like injury dynamics (closed head injury, reproduction of both linear and rotational forces) and induction of transient pain-like features followed by a long-lasting (persistent) period of increased vulnerability to normally innocuous stimuli that may reinstate a headache-like response. This method may be used to investigate the underlying pathological mechanisms involved in the transition of APTH to PPTH and the evaluation of novel therapeutic strategies for the treatment or prevention of APTH and PPTH.
