Deployment-Related Mild Traumatic Brain Injury (mTBI): Incidence Natural History and Predictors of Recovery in Soldiers Returning from OIF/OEF
Abstract
The primary objective of this proposal is to identify perineural drug combinations that will enhance pain relief by producing long-duration, sensory-specific nerve block with minimal toxicity. Therefore, we proposed to assess the efficacy of the adjuvants clonidine, buprenorphine, dexamethasone, and midazolam, alone and in combination with local anesthetics, in the block of peripheral nerve in vitro (Aim 1) and in vivo (Aim 2). Results of the first set of in vitro experiments indicate that midazolam blocks C-fibers with greater potency and efficacy than A-fibers, consistent with a sensory-specific mode of action. Clonidine blocks A- and Cfibers, but only at concentrations greater than those associated with systemic side effects in vivo. Dexamethasone and buprenorphine blocked neither C- nor A-fibers at clinically relevant concentrations. The combination of buprenorphine, clonidine and dexamethasone had no influence on either local anesthetic- or midazolam-induced nerve block. Because midazolam acts at both peripheral and central benzodiazepine receptors, midazolam results suggest the potential to maximize sensory-specific block and minimize toxicity with selective activation/inhibition of these receptor classes. Because the other adjuvants prolong local anesthetic-induced block in vivo, the failure to detect an influence of this drug combination on isolated nerves in vitro suggests that the drug interaction involves mechanisms extrinsic to peripheral nerve axons.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA567355
Entities
People
- Karen Schwab
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine