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Quality of Life Research

, Volume 19, Issue 10, pp 1407–1417 | Cite as

Biological pathways and genetic variables involved in pain

  • Qiuling Shi
  • Charles S. Cleeland
  • Pål Klepstad
  • Christine Miaskowski
  • Nancy L. Pedersen
Article

Abstract

Purpose

This paper summarizes current knowledge of pain-related and analgesic-related pathways as well as genetic variations involved in pain perception and management.

Methods

The pain group of the GENEQOL Consortium was given the task of summarizing the current status of research on genetic variations in pain and analgesic efficacy. This review is neither exhaustive nor comprehensive; we focus primarily on single-nucleotide polymorphisms.

Results

Two categories of potential genetic pain-perception pathways were identified: neurotransmission modulators and mechanisms that affect inflammation. Four categories were identified for analgesic efficacy: genes related to receptor interaction, modulation of opioid effects, metabolism, and transport. Various genetic variations involved in these pathways are proposed as candidate genetic markers for pain perception and for individual sensitivity to analgesics.

Conclusions

Candidate gene association studies have been used to provide evidence for the genetic modulation of pain perception and response to analgesics. However, the nature and range of genetic modulation of pain is not well addressed due to the limited number of patients and the limited number of genes and genetic variants investigated in studies to date. Moreover, personalized analgesic treatments will require a more complete understanding of the effects of genetic variants and gene–gene interactions in response to analgesics.

Keywords

Pain Analgesic efficacy Genetic polymorphism Biological pathways 

Abbreviations

5-HT

5-Hydroxytryptamine (serotonin)

5-HTT

Serotonin transporter

5-HTTLPR

Serotonin transporter gene repeated polymorphism

A

Adenosine

ABCB1

Adenosine-5′-triphosphate-binding cassette sub-family B member 1

C

Cytidine

CNS

Central nervous system

COMT

Catechol-O-methyltransferase

CYP2C9

Cytochrome P450 2C9

CYP2D6

Cytochrome P450 2D6

DNA

Deoxyribonucleic acid

FAAH

Fatty acid amide hydrolase

G

Guanosine

GABA

Gamma amino butyric acid

GCH1

Guanosine triphosphate cyclohydrolase 1

IL-1

Interleukin 1

IL-1RN

Interleukin 1 receptor antagonist

IL-1α

Interleukin 1α

IL-1β

Interleukin 1β

IL-6

Interleukin 6

IL-8

Interleukin 8

MC1R

Melanocortin 1 receptor

mRNA

Messenger ribonucleic acid

NSAID

Nonsteroidal anti-inflammatory drug

OPRM1

μ-Opioid receptor gene

P-gp

P-Glycoprotein

SNP

Single-nucleotide polymorphism

T

Thymidine

TNF-α

Tumor necrosis factor α

TRP

Transient receptor potential

TRPA1

Transient receptor potential cation channel, subfamily A, member 1

TRPV1

Transient receptor potential cation channel, subfamily V, member 1

UGT

Uridine 5′-diphospho-glucuronosyltransferase

UGT2B7

UDP-Glucuronosyltransferase-2B7

Notes

Acknowledgments

The authors thank Drs. Jeff Sloan and Mirjam A. G. Sprangers for arranging the February 2009 GENEQOL Consortium, a two-day workshop that brought together experts in quality-of-life research, genetics, and pain medicine. The authors acknowledge the editorial assistance of Jeanie F. Woodruff, ELS.

Glossary

Allele

One of various forms of a gene, usually referring to a specific genetic locus

Allodynia

Pain produced by a stimulus that does not normally provoke pain, i.e., pressure from clothing or simple touch

Base

The essential basic component of DNA or RNA. There are four DNA bases: adenine (A), guanine (G), thymine (T), and cytosine (C)

Candidate gene association study

A method that determines whether a particular form of a DNA polymorphism occurs more frequently in subjects with a phenotype of interest, usually focusing on genes involved in the biological pathways of disease development and treatment

Chromosome

Thread-like structures of DNA found in the nucleus of a cell that carry hereditary information

Genome

The entire hereditary information of an organism

Genome-wide association study

A method to examine genetic variation across a given genome, designed to identify genetic associations with phenotypes of interest, usually 1,000,000 or more markers involved

Genotype

Instructions of the internal inheritable information of any living organism

Haplotype

A set of genetic markers in the same chromosome that highly correlate to each other and tend to be inherited together

Heterozygote

An organism with two different alleles at one gene location

Homozygote

An organism with two identical alleles at one gene location

Hyperalgesia

Increased pain sensitivity, usually abnormal

Nociception

Perception of pain

Nonsynonymous SNP

A DNA base change that results in an altered polypeptide sequence

Phenotype

Anything that is part of the observable structure, function, or behavior of a living organism

Polymorphism

Variety in forms of a particular DNA sequence in a population

SNP

Short form for single-nucleotide polymorphism, a variation between individuals in a single nucleotide (A, T, C, or G) of the DNA sequence

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Qiuling Shi
    • 1
  • Charles S. Cleeland
    • 1
  • Pål Klepstad
    • 2
  • Christine Miaskowski
    • 3
  • Nancy L. Pedersen
    • 4
  1. 1.Department of Symptom ResearchThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of AnesthesiologyUniversity Hospital of TrondheimTrondheimNorway
  3. 3.Department of Physiological NursingUCSF School of NursingSan FranciscoUSA
  4. 4.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden

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