Toxicogenomic analysis of a sustained release local anesthetic delivery system. Biomaterials 2012 May;33(13):3586-93
Date
02/22/2012Pubmed ID
22341215Pubmed Central ID
PMC3288387DOI
10.1016/j.biomaterials.2012.01.043Scopus ID
2-s2.0-84857441486 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Concerns over neurotoxicity have impeded the development of sustained release formulations providing prolonged duration local anesthesia (PDLA) from a single injection, for which there is an urgent clinical need. Here, we have used toxicogenomics to investigate whether nerve injury occurred during week-long continuous sciatic nerve blockade by microspheres containing bupivacaine, tetrodotoxin, and dexamethasone (TBD). Animals treated with amitriptyline solution (our positive control for local anesthetic-associated nerve injury) developed irreversible nerve blockade, had severely abnormal nerve histology, and the expression of hundreds of genes was altered in the dorsal root ganglia at 4 and 7 days after injection. In marked contrast, TBD-treated nerves reverted to normal function, were normal histologically and there were changes in the expression of a small number of genes. Toxicogenomic studies have great potential in delineating patterns of gene expression associated with specific patterns of tissue injury (e.g. amitriptyline neurotoxicity), and in identifying related changes in gene expression upon exposure to a drug, biomaterial, or drug delivery system.
Author List
Shichor I, Shomron N, Lawlor MW, Bae SA, Zoldan J, Langer R, Kohane DSAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmitriptylineAnesthetics, Local
Animals
Bupivacaine
Delayed-Action Preparations
Dexamethasone
Gene Expression Regulation
Lactic Acid
Male
Microspheres
Polyglycolic Acid
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Reproducibility of Results
Sciatic Nerve
Tetrodotoxin
Toxicogenetics
