Abstract

Pain sensitivity and response to pain inhibiting strategies exhibit large individual differences. The genetic portion of such variability can be studied using inbred mouse strains. The underlying genes can be localized and eventually identified using QTL mapping. In an attempt to explain the genetic factors underlying such variability, we propose to perform QTL mapping of four different analgesics: acetaminophen, epbatidine, U50-488, and WIN-55,212-2. Although these analgesics interact with distinct proteins, there exists a moderate to strong correlation among inbred strain responses to them, suggesting that """"""""master"""""""" analgesia genes may be identified affecting all types of analgesia. Once QTLs are detected, we will attempt to learn their identity by a combination of candidate gene and positional cloning strategies. Clinical utility of this work may include the development of DNA tests predicting sensitivity to analgesics, novel therapies, and possibly gene therapy for chronic pain states.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015191-02
Application #
6515967
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (01))
Program Officer
Rutter, Joni
Project Start
2001-09-22
Project End
2006-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$225,000
Indirect Cost

  Institution

Name
Mcgill University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 0-G4

  Publications

Young, E E; Bryant, C D; Lee, S E et al. (2016) Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test. Genes Brain Behav 15:604-15
Mogil, Jeffrey S; Sorge, Robert E; LaCroix-Fralish, Michael L et al. (2011) Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction. Nat Neurosci 14:1569-73
Smith, Shad B; Marker, Cheryl L; Perry, Cydne et al. (2008) Quantitative trait locus and computational mapping identifies Kcnj9 (GIRK3) as a candidate gene affecting analgesia from multiple drug classes. Pharmacogenet Genomics 18:231-41
Green, Amanda D; Young, Katrina K; Lehto, Sonya G et al. (2006) Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse. Pain 124:50-8
Mogil, Jeffrey S; Ritchie, Jennifer; Sotocinal, Susana G et al. (2006) Screening for pain phenotypes: analysis of three congenic mouse strains on a battery of nine nociceptive assays. Pain 126:24-34
Mogil, Jeffrey S; Breese, Nicole M; Witty, Marie-France et al. (2005) Transgenic expression of a dominant-negative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli. J Neurosci 25:9893-901
Mogil, J S; Ritchie, J; Smith, S B et al. (2005) Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet 42:583-7
Mogil, Jeffrey S; Smith, Shad B; O'Reilly, Meghan K et al. (2005) Influence of nociception and stress-induced antinociception on genetic variation in isoflurane anesthetic potency among mouse strains. Anesthesiology 103:751-8
Mogil, Jeffrey S; Miermeister, Frank; Seifert, Frank et al. (2005) Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proc Natl Acad Sci U S A 102:12938-43
Nemmani, Kumar V S; Lalonde, Jasmin; Mogil, Jeffrey S (2005) Region-specific changes of calcium/calmodulin-dependent protein kinase IV in the mouse brain following chronic morphine treatment. Neuroreport 16:879-82

Showing the most recent 10 out of 18 publications