The overall goal of this project is to understand the mechanisms underlying preemptive analgesia, an important process in preventing the establishment of pain pathways/cycles. This problem is critical for treating general pain states which affect millions of people each year. The investigator plans to characterize the biochemical and molecular basis of anesthetic mediated antinociception. Some anesthetic agents are known to provide preemptive analgesia (nitrous oxide, morphine, pentobarbital) and others do not (halothane and isoflurane).
Specific aims therefore include comparison of these agents with regard to: 1) inhibition of primary afferent neurotransmission; 2) inhibition of the activity and/or expression of intracellular mediators/markers of pain induced neuroplasticity such as nitric oxide and Fos; and 3) stimulation of opioid effects as potential mechanisms of anesthetic mediated preemptive analgesia. In addition, in vivo administration of antisense oligonucleotides will be used to inhibit synthesis of specific cellular proteins of putative importance for pain in order to elucidate directly potential molecular sites of anesthetic mediated antinociception. The goal is to enhance current understanding of the mechanisms involved in preemptive analgesia and to shed light on possible clinical approaches to the treatment of pain.
