Genetics

Mice, like humans, show robust individual differences in their sensitivity to pain, pain inhibition, and susceptibility to chronic pain development after injury. Like all biological traits, some proportion of this variability is due to inherited genetic factors ("nature"), some proportion is due to environmental factors ("nurture"), and some proportion is due to the interaction of the two. The identification of the genes responsible for variability in pain traits is accomplished by quantitative trait locus (QTL) mapping followed by some combination of candidate gene testing and/or positional refinement of the QTL region. It's important to note that these "pain variability genes" represent a subset of all "pain genes," defined simply as genes coding for proteins of relevance to pain. The latter type of pain gene can be identified via conventional techniques, transgenic knockout experiments, and microarray gene expression profiling. A compilation of pain genes as defined by transgenic knockout experiments is provided in the Resources (Pain Genes Db) section of this website

Using these techniques, the Pain Genetics Lab and collaborators have provided published evidence for the following genomic regions (and genes) associated with variability in pain.

Trait

Genomic
Location

Sex
Specificity?

Likely Gene

Hot Plate Test

Chr. 4, 70 cM

Male>Female

Oprd1 (delta-opioid receptor)

Formalin Test

Chr. 9, 60 cM

No

Atp1b3 (beta-3 subunit of the sodium-potassium pump)

 

Chr. 14, 33 Mb

No

Mapk8 (mitogen-activated protein kinase 8)

 

Chr.10, 70 cM

Male>Female

Avpr1a (vasopressin receptor 1A)

Paw-Withdrawal Test

Chr. 7, 55 cM

Female>Male

Calca (CGRP)

 

Chr. 4, 80 Mb

No

Tyrp1 (tyrosinase-related protein 1)

Spared Nerve Injury

Chr. 5, 123 Mb

No 

P2rx7 (purinergic P2X7 receptor)

Morphine Analgesia

Chr. 1, 10 cM

Female Only

???

 

Chr. 9, 20 cM

Female Only

???

 

Chr. 9, 40 cM

No

Htr1b (5-HT receptor,1B)

 

Chr. 10, 10 cM

Male>Female

Oprm1 (mu-opioid receptor)

U50,488 (kappa-opioid)
Analgesia

Chr. 8, 65 cM

Female Only

Mc1r (melanocortin-1 receptor

Multiple Analgesic Classes

Chr. 1, 95 cM

No

Kcnj9 (GIRK3; Kir3.3)

 

 The Pain Genetics Lab continues to work towards the identification of genomic regions associated with variability in pain-related traits, and in the identification of the responsible genes within these regions. Current projects are focused on genes relevant to mechanical allodynia after nerve injury and chronic inflammation. In addition to our QTL mapping efforts, much can be learned about pain by examining genetic correlations among pain-related traits. We have tested a common set of 12 inbred mouse strains (all genetically identical "clones" of each other) for many, many types of pain, analgesia, and related traits (including tolerance, dependence, itch). Traits in which the same strains are sensitive and resistant are traits in which variability is mediated by common genes, and thus common physiology. We have used genetic correlation analysis to define primary or fundamental types of pain, to infer the existence of "master" analgesia genes, and to demonstrate that the potency of analgesics in mice is dependent on the type of pain being inhibited.

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Department of Psychology 
McGill University 
1205 Dr. Penfield Avenue, Rm. N7/42
Montreal, QC  H3A 1B1

Canada  

jeffrey.mogil@mcgill.ca
Tel.  514.398.6085
Fax.  514.398.4896
Lab.  514.398.2742
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