Mechanisms and treatments of chronic pain after traumatic brain injury

While pain after trauma generally resolves, some trauma patients experience pain for months to years after injury. An example, relevant to both combat and civilian settings, is chronic pain after traumatic brain injury (TBI). Headache as well as pain in the back and extremities are common locations for TBI-related chronic pain to be experienced. TBI-related pain can exist alone or can exacerbate pain from other injuries long after healing has occurred. Consequences of chronic pain in these settings include increased suffering, higher levels of disability, serious emotional problems, and worsened cognitive deficits. The current review will examine recent evidence regarding dysfunction of endogenous pain modulatory mechanisms, neuroplastic changes in the trigeminal circuitry and alterations in spinal nociceptive processing as contributors to TBI-related chronic pain. Key pain modulatory centers including the locus coeruleus, periaqueductal grey matter, and rostroventromedial medulla are vulnerable to TBI. Both the rationales and existing evidence for the use of monoamine reuptake inhibitors, CGRP antagonists, CXCR2 chemokine receptor antagonists, and interventional therapies will be presented. While consensus guidelines for the management of chronic post-traumatic TBI-related pain are lacking, several approaches to this clinically challenging situation deserve focused evaluation and may prove to be viable therapeutic options.