Pharmacological Enhancement of Cortical Activity for Controlling Chronic Pain
Abstract
Chronic pain is a major problem of public health in both civilians and military personnel. Patients with neuropathic pain often experience severe pain that is often refractory to current treatment options. The chronic pain not only severely compromises quality of life, employment, and recovery, but also leads to opioid addiction and life-threatening drug overdose and abuse. Because the lesions or injuries that lead to neuropathic pain initially cause loss of nervous sensory input to the brain, a recent hypothesis proposes that a compensatory reaction and plasticity (termed homeostatic plasticity) is responsible for developing and maintaining the pain. If this is true, then stimulating brain activity to replenish the lost sensory input should help the body to recovery the lost activity and control the pain. The goal of this research proposal is to develop a new treatment option by enhancing the activity of nerve cells in the related areas of the brain. Specifically, we will test a compound that are known to mildly enhance neuronal activity in the brain (but without overactivating neurons to cause seizures). In a well-established nerve injury model in mice that usually causes neuropathic pain, we will first determine whether the drugs will reduce pain sensation to mechanical and thermal stimulation and spontaneous pain. Then we will use imaging techniques to examine activities of individual neurons as well as the whole cerebral cortex in live animals, which will tell us whether and how the drugs affect brain activity. We may also record electrical activity from single brain neurons to understand how the drugs affect single neurons and the input they receive from synapses. Findings from this study have the potential to open new avenues for pain treatment and to limit the amount of medication that is needed for effective pain relief. Because pain is often a major factor limiting the quality of life of neurological patients in Soldiers and Veterans, we expect that this study will contribute to better patient care and reduce the use of opioids and its lethal side effects.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910114XX0
Entities
People
- Xiaoming Jin
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army