Biological pathways and genetic variables involved in pain.
OBJECTIVE
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.
Shi
Qiuling
Q
Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1450, Houston, TX 77030, USA. qshi@mdanderson.org
Cleeland
Charles S
CS
Klepstad
Pål
P
Miaskowski
Christine
C
Pedersen
Nancy L
NL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000700:Analgesics / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D010146:Pain / Q000188:drug therapy* / Q000235:genetics*; D058748:Pain Perception; D020641:Polymorphism, Single Nucleotide; D009435:Synaptic Transmission / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000700:Analgesics; D003577:Cytochrome P-450 Enzyme System