Pain and the genome

  • M. E. Ferrero
  • A. Fulgenzi
  • M. Tiengo
Part of the Topics in Anaesthesia and Critical Care book series (TIACC)


There is increasing evidence that genotype affects pain sensitivity and pain modulation. As an example in humans, 10% of a Caucasian population studied only poorly metabolized the liver isozyme P450IID6 (required for the O-demethylation of the widely used opiate drug codeine to morphine) [1]. So, for such people codeine is an inefficient analgesic. The enzymatic defect is related to a mutation in the CYP2D6 gene [2]. As an experimental example, a recent study in rats demonstrated that a form of stress-induced analgesia was naloxone-insensitive, but attenuated by dizocilpine in male C57BL/6J mice. The same type of analgesia in male DBA/2J mice was significantly attenuated by naloxone but was insensitive to dizocilpine antagonism, indicating the role exerted by the different rat strain (i.e., genetic factors) in determining the selective recruitment of alternative central mechanisms of pain inhibition [3].


Nerve Growth Factor Carpal Tunnel Syndrome CYP2D6 Gene Nerve Growth Factor Expression Hereditary Sensory Neuropathy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alvan G, Bechtel P, Isehus L et al (1990) Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 39: 533–537PubMedCrossRefGoogle Scholar
  2. 2.
    Dayer P, Desmeules J, Leemann T et al (1988) Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufl). Biochem Biophys Res Commun 152: 411–416PubMedCrossRefGoogle Scholar
  3. 3.
    Mogil JS, Belknap JK (1997) Sex and genotype determine the selective activation of neurochemically-distinct mechanisms of swin stress-induced analgesia. Pharmacol Biochem Behav 56 (1): 61–66PubMedCrossRefGoogle Scholar
  4. 4.
    Mogil JS, Sternberg WF, Marek P et al (1996) The genetics of pain and pain inhibition. Proc Natl Acad Sci USA 93: 3048–3055PubMedCrossRefGoogle Scholar
  5. 5.
    Rubinstein M, Mogil IS, Japon M et al (1996) Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis. Proc Natl Acad Sci 93(9).3995–4000Google Scholar
  6. 6.
    Mogil JS, Kest B, Sadowski B, Belknap PK (1996) Differential genetic mediation of sensitivity to morphine in genetic models of opiate antmociception: influence of nociceptive assay. J Pharmacol Exp Ther 276: 532–544PubMedGoogle Scholar
  7. 7.
    Akopian AN, Abson NC, Wood JN (1996) Molecular genetic approaches to nociceptor development and function. Trends Neurosci 19 (6): 240–246PubMedCrossRefGoogle Scholar
  8. 8.
    Levi Montalcini R (1987) The nerve growth factor: thiry five years later EMBO J 6.11451154Google Scholar
  9. 9.
    Thoenen H (1991) The changing scene of neurotrophic factors. Trends Neurosci 14: 165170CrossRefGoogle Scholar
  10. 10.
    Hefti F, Hartikka J, Knusel B (1989) Function of neurotrophic factors in the adult and agin brain and their possible use in the treatment of neurodegenerative diseases Neurobiol Aging 10: 515–533Google Scholar
  11. 11.
    Crowley C, Spencer SD, Nishimura MC et al (1994) Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain chohnergic neurons. Cell 76: 1001–1011PubMedCrossRefGoogle Scholar
  12. 12.
    Smeyne RJ, Klein R, Schnapp A et al (1994) Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 368: 246–249PubMedCrossRefGoogle Scholar
  13. 13.
    Indo Y,Tsuruta M,Hayashida Y et al(1996)Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis.Nature Genet 13:485488CrossRefGoogle Scholar
  14. 14.
    Wood JN (1996) No pain, some gain. Nature Genet 13: 382–383PubMedCrossRefGoogle Scholar
  15. 15.
    Ehrhard PB, Erb P, Graumann U et al (1993) Expression of nerve growth factor and receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Natl Acad Sci USA 90: 10984–10998PubMedCrossRefGoogle Scholar
  16. 16.
    Ferreira SH, Lorenzetti BB, Bristow AF et al (1988) Interleukrn 113 as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature 334: 698–700PubMedCrossRefGoogle Scholar
  17. 17.
    Watkins LR, Wiertelak E, Goehler LE et al (1994) Characterization of cytokine-induced hyperalgesia. Brain Res 654: 15–26PubMedCrossRefGoogle Scholar
  18. 18.
    Xu XJ,Hao IX,Jonsson SV et al(1997)Nociceptive responses in interleukm-6-deficient mice to peripheral inflammation and peripheral nerve section.Cytokine 9(12):10281033CrossRefGoogle Scholar
  19. 19.
    Kincy-Cain T, Bost KL (1997) Substance P-Induced IL-12 production by murine macrophages. J Immunol 158: 2334–2339PubMedGoogle Scholar
  20. 20.
    Devor M, Raber P (1991) Experimental evidence of a genetic predisposition to neuropathic pain. Eur J Pain 12 (3): 65–68Google Scholar
  21. 21.
    Moos M et al (1988) Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectm. Nature 334: 701–703PubMedCrossRefGoogle Scholar
  22. 22.
    Dahme M,Bartsch U,Martini R et al(1997)Disruption of the mouse Ll gene leads to malformations of the nervous system.Nature Genet 17.346–349PubMedCrossRefGoogle Scholar

Copyright information

© Springer Verlag Italia, Milano 1999

Authors and Affiliations

  • M. E. Ferrero
  • A. Fulgenzi
  • M. Tiengo

There are no affiliations available

Personalised recommendations