Microglia Contribute to Ongoing Pain Caused by TBI
Abstract
As a result of aggressive interventions and rehabilitation, traumatic brain injury (TBI) patients live longer, but commonly live with intractable pain due to the limited interventions available to manage chronic pain. Patients with TBI experience several chronic pain conditions and include headache (often migraine) and neuropathic pain, defined as pain initiated or caused by a primary lesion or dysfunction of the nervous system. Pain is a multidimensional experience and the negative affect, or how much the pain is "bothersome," significantly impacts the quality of life of the sufferer, where the emotional component has been argued to be a greatest metric of quality of life. In fact, chronic pain is second only to bipolar disorder as the major cause of suicide among all medical illnesses. Understanding the processes that influence the emotional/unpleasant component of pain is essential to developing novel treatment strategies. Because it is common for chronic pain to be comorbid with diseases known to have deficits in the brain chemical dopamine (e.g., depression), it is posited that dysfunction of dopamine signaling also contributes to the genesis of chronic pain. Our proposal focuses on understanding how microglia, a non-neuronal immune cell, causes pain after a TBI. Targeting microglial activation represents a timely and feasible therapeutic target to reduce the negative affective states associated with TBI. We will use novel drug treatments to inhibit microglial activation and a drug that restores inhibitory neurotransmission and was shown to reverse neuropathic pain symptoms following peripheral nerve injury. Significance: The proposed research will provide insights into how microglial activation modulates pain and emotional brain circuitry after TBI. Research investigating how TBI-induced pain is altered by microglia will greatly broaden our understanding of this disease and identify novel therapeutic targets to treat pain in this population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510435
Entities
People
- Catherine M. Cahill
Organizations
- Naval Information Warfare Center Pacific
- United States Army