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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM042466-06
Application #
2668473
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1989-08-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Lee, Il-Ok; Yukhananov, Rustam; Standaert, David G et al. (2004) NMDA-R1 antisense oligodeoxynucleotides modify formalin-induced nociception and spinal c-Fos expression in rat spinal cord. Pharmacol Biochem Behav 79:183-8
Yukhananov, Rus; Guan, Jane; Crosby, Gregory (2002) Antisense oligonucleotides to N-methyl-D-aspartate receptor subunits attenuate formalin-induced nociception in the rat. Brain Res 930:163-9
Loguinov, A V; Anderson, L M; Crosby, G J et al. (2001) Gene expression following acute morphine administration. Physiol Genomics 6:169-81
Crosby, G; Marota, J J; Goto, T et al. (1994) Subarachnoid morphine reduces stimulation-induced but not basal expression of preproenkephalin in rat spinal cord. Anesthesiology 81:1270-6
Goto, T; Marota, J J; Crosby, G (1994) Pentobarbitone, but not propofol, produces pre-emptive analgesia in the rat formalin model. Br J Anaesth 72:662-7
Goto, T; Marota, J J; Crosby, G (1994) Nitrous oxide induces preemptive analgesia in the rat that is antagonized by halothane. Anesthesiology 80:409-16
Marota, J J; Crosby, G; Uhl, G R (1992) Selective effects of pentobarbital and halothane on c-fos and jun-B gene expression in rat brain. Anesthesiology 77:365-71