Human pain causes untold misery and suffering, with major impact on functioning and resources. Recent advances in genetics have revealed that subtle changes in DNA could partly explain the variation in individual differences in pain. Various genes encoding for receptors are now known to play a major role in the sensitivity, perception and expression of pain. The fields of epigenetics and proteomics hold promises in the way pain could be treated and managed in future.
YoungEELariviereWRBelferI. Genetic basis of pain variability. J Med Genet2012; 49(1): 1–19.
2.
FaucettJGordonNLevineJ. Differences in postoperative pain severity among four ethnic groups. J Pain Symptom Manage1994; 9: 383–389.
3.
FillingimRB. Sex, gender and pain: women and men really are different. Curr Rev Pain2000; 4: 24–30.
4.
DornerTEMuckenhuberJStroneggerWJ. The impact of socio-economic status on pain and the perception of disability due to pain. Eur J Pain2011; 15: 103–109.
5.
DiatchenkoLSladeGDNackleyAG. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet2005; 14: 135–143.
6.
Lacroix-FralishMLMogilJS. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol2009; 49: 97–121.
7.
A haplotype map of the human genome. The International HapMap Consortium. Nature2005; 437: 1299–1320.
8.
VenterJCAdamsMDMyersEW. The sequence of the human genome. Science2001; 291: 1304–1351.
9.
DevorM. Chapter 23. What are pain genes and why are they interesting? In: MogilJ (ed.) Pain (An updated review). Seattle, WA: IASP Press, 2010, pp. 227–237.
10.
NorburyTAMacGregorAJUrwinJ. Heritability of responses to painful stimuli in women: a classical twin study. Brain2007; 130: 3041–3049.
11.
WilliamsFMSpectorTDMacGregorAJ. Pain reporting at different body sites is explained by a single underlying genetic factor. Rheumatology (Oxford)2010; 49: 1753–1755.
12.
YuFHCatterwallWA. Overview of the voltage-gated sodium channel family. Genome Biol2003; 4: 207.
13.
WangWGuJLiY-Q. Are voltage-gated sodium channels on the dorsal root ganglion involved in the development of neuropathic pain?Mol Pain2011; 7: 16.
14.
De vriesBFrantsRRFerrariMD. Molecular genetics of migraine. Hum Genet2009; 126: 115–132.
15.
DrenthJPWaxmanSG. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J Clin Invest2007; 117: 3603–3609.
16.
HoeijmakersJGFaberCGLauriaG. Small-fiber neuropathies – advances in diagnosis, pathophysiology and management. Nat Rev Neurol2012; 8: 369–379.
17.
FaberCGHoeijmakersJGAhnHS. Gain-of-function mutation in idiopathic small fiber neuropathy. Ann Neurol2012; 71: 26–39.
18.
FaberCGLauriaGMerkiesISJ. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A2012; 109(47): 19444–19449.
19.
DuanGXiangGZhangX. A single nucleotide polymorphism in SCN9A may decrease postoperative pain sensitivity in the general population. Anesthesiology2013; 118(2): 436–442.
20.
CoxJJReimannFNicholasAK. An SCN9A channelopathy causes congenital inability to experience pain. Nature2006; 444: 894–898.
21.
NagasakoEMOaklanderALDworkinRH. Congenital insensitivity to pain: an update. Pain2003; 101: 213–219.
22.
Dib-HajjSDRushAMCumminsTR. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain2005; 128: 1847–1854.
DiatchenkoLNackleyAGTchivilevaIE. Genetic architecture of human pain perception. Trends Genet2007; 23: 605–613.
26.
TegederIAdolphJSchmidtH. Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype. Eur J Pain2008; 12: 1069–1077.
27.
LotschJKlepstadPDoehringA. A GTP cyclohydrolase 1 genetic variant delays cancer pain. Pain2010; 148: 103–106.
28.
AmayaFWangHCostiganM. The voltage-gated sodium channel Nav1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci2006; 26: 12852–12860.
29.
ChangPFArendt-NielsenLGraven-NielsenT. Psychophysical and EEG responses to experimental muscle pain in humans: pain intensity encodes EEG activity. Brain Res Bull2003; 59: 533–543.
30.
BuskilaD. Genetics of chronic pain states. Best Pract Res Clin Rheumatol2007; 21: 535–547.
31.
ZubietaJKSmithYRBuellerJA. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science2001; 293: 311–315.
32.
NackleyAGTanKSFechoK. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta-2 and beta-3-adrenergic receptors. Pain2007; 128: 199–208.
33.
HockingLJSmithBHJonesGT. Genetic variation in the beta2-adrenergic receptor, but not COMT predisposes to chronic pain: results from the 1958 British Birth Cohort Study. Pain2010; 149: 143–151.
34.
TegederICostiganMGriffinRS. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med2006; 12: 1269–1277.
35.
IchinoseHSuzukiTInagakiH. Molecular genetics of dopa-responsive dystonia. Biol Chem1999; 380: 1355–1364.
36.
OertelBLotschJ. Genetic mutations that prevent pain: implications for future pain medication. Pharmacogenetics2008; 9(2): 179–194.
37.
Reyes-GibbyCCSheteSRakvagT. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain2007; 130: 25–30.
38.
AngstMSKoppertWPahlI. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain2003; 106: 49–52.
39.
JolyVRichebePGuignardB. Remifentanil-induced post-operative hyperalgesia and its prevention with small dose ketamine. Anesthesiology2005; 103: 147–155.
40.
GuoTMLiuMZhangYG. Association between Caspase-9 promoter region polymorphisms and discogenic back low back pain. Connect Tissue Res2011; 52: 133–138.
41.
BinderAMayDBaronR. Transient receptor potential channel polymorphism are associated with the somatosensory function in neuropathic pain patients. PLoS One2011; 6(3): e17387.
42.
GanXLLinYHZhangY. Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. DNA Cell Biol2010; 29: 663–667.
43.
DenkFMcMahonSB. Chronic pain: emerging evidence for the involvement of epigenetics. Neuron2012; 73: 435–444.
44.
BuchheitTVan de VenTShawA. Epigenetics and the transition from acute to chronic pain. Pain Med2012; 13: 1474–1490.
45.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. The Wellcome Trust Case Control Consortium. Nature2007; 447: 661–678.
46.
TegederILotschJ. Current evidence for a modulation of low back pain by human genetic variants. J Cell Mol Med2009; 13(88): 1605–1619.
47.
NissenbaumJ. From mouse to humans: discovery of the CACNG2 pain susceptibility gene. Clin Genet2012; 82: 311–320.
48.
RebsamenMCDesmeulesJDaaliY. The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J2009; 9: 34–41.
49.
GoldbergYPPriceNNamdariR. Treatment of Nav1.7 mediated pain in inherited erythromelalgia using a novel sodium channel blocker. Pain2012; 153: 80–85.
50.
BeutlerASReinhardtM. AAV for pain: steps towards clinical translation. Gene Ther2009; 16: 461–469.
51.
HandyCRKrudyCBoulisN. Gene therapy: a potential approach for cancer pain. Pain Res Treat2011; 2011: Article ID 987597 (12 pp.).
52.
WolfeDMattaMFinkDJ. A human trial of HSV mediated gene transfer for the treatment of chronic pain. Gene Ther2009; 16(4): 455–460.
53.
FinkDJWechuckJMataM. Gene therapy for pain: results of a phase I clinical trial. Ann Neurol2011; 70(2): 207–212.
54.
Clinical Trial.govIdentifier: NCT01291901.
55.
FranchiSValsecchiAEBorsaniE. Intravenous neural stem cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy. Pain2012; 153: 850–861.