Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain

Abstract Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a “protective” (i.e., less pain) haplotype in the GTP cyclohydrolase (GCH1) gene, other research has failed to confirm this association. Possibly, the effects of single nucleotide polymorphisms (SNPs) vary depending on the pain task. The current investigation analyzed the association of five previously identified GCH1 SNPs with ratings of pain induced by topical high concentration (10%) capsaicin applied to the skin of 39 healthy human volunteers. Each of the GCH1 polymorphisms was associated with lower pain ratings. When combined, three of the five accounted for a surprisingly high 35% of the inter‐individual variance in pain ratings. We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin.

[1]  R. Edwards,et al.  Individual differences in endogenous pain modulation as a risk factor for chronic pain , 2005, Neurology.

[2]  L. Cardon,et al.  Population stratification and spurious allelic association , 2003, The Lancet.

[3]  R. Fillingim,et al.  Ethnic differences and responses to pain in healthy young adults. , 2005, Pain medicine.

[4]  J. Lötsch,et al.  Genetic mutations that prevent pain: implications for future pain medication. , 2008, Pharmacogenomics.

[5]  R. Dionne,et al.  Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans , 2007, Molecular pain.

[6]  J. Lötsch,et al.  Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype , 2008, European journal of pain.

[7]  O. Vassend,et al.  Individual differences in pain sensitivity: Genetic and environmental contributions , 2008, PAIN.

[8]  J. Lötsch,et al.  Current evidence for a modulation of nociception by human genetic polymorphisms , 2007, Pain.

[9]  R. Fillingim,et al.  Ethnic differences in responses to multiple experimental pain stimuli , 2005, Pain.

[10]  R. Edwards,et al.  Genetic predictors of acute and chronic pain , 2006, Current rheumatology reports.

[11]  Robert R. Edwards,et al.  Quantitative assessment of experimental pain perception: multiple domains of clinical relevance , 2005, Pain.

[12]  R. Meyer,et al.  Capsaicin Responses in Heat-Sensitive and Heat-Insensitive A-Fiber Nociceptors , 2001, The Journal of Neuroscience.

[13]  J. Zubieta,et al.  Placebo effects on human μ-opioid activity during pain , 2007, Proceedings of the National Academy of Sciences.

[14]  R. Dannals,et al.  Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET) , 2002, Pain.

[15]  Jörn Lötsch,et al.  GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence , 2006, Nature Medicine.

[16]  D. Julius,et al.  The vanilloid receptor: a molecular gateway to the pain pathway. , 2001, Annual review of neuroscience.

[17]  J. Lötsch,et al.  Principle components analysis of pain thresholds to thermal, electrical, and mechanical stimuli suggests a predominant common source of variance , 2008, PAIN.

[18]  Badreddine Bencherif,et al.  Naloxone increases pain induced by topical capsaicin in healthy human volunteers , 2002, PAIN.

[19]  M. Tominaga,et al.  Nitric oxide activates TRP channels by cysteine S-nitrosylation , 2006, Nature chemical biology.

[20]  M. Max,et al.  Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms. , 2007, Clinical chemistry.