A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4)
Technical Report,30 Sep 2015,29 Sep 2016
Regents of the University of Colorado Boulder United States
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Spinal cord injury SCI is a disabling and costly condition affecting wounded military personnel 1. SCI is also one of the leading causes of central neuropathic pain, and military personnel that sustain SCI in the field by improvised explosive devices IEDs, grenades, gunshot wounds, etc. are at an even greater risk of developing chronic pain as well as emotional symptoms due to the polytraumatic nature of these injuries 2. Furthermore, central neuropathic pain in general is often intractable to treatment current therapies including opioids only provide similar to 50 pain relief in 1 out of 2-3 people 3 and the therapies are even less effective in military blast SCI due to the complexity of the injury 4. This level of treatment efficacy is unacceptable for war fighters, military personnel, veterans, and citizens as a whole. SCI patients are almost universally treated with opioids as a first-line treatment, but recent evidence in the animal literature and recently in the clinical literature indicates that opioid administration after traumatic injury can have deleterious consequences. This proposal will test a clinically relevant therapeutic, -naltrexone, that we predict will improve the efficacy of opioids for controlling SCI below-level pain while decreasing the negative consequences of opioid use. We predict that the mechanism by which -naltrexone exerts at least some of its effects is via toll-like receptor 4. Thus our aim is to improve the quality of life for service-members, veterans, caretakers, and the general population.
- Medicine and Medical Research