Pain Genetics and Personalized Spine Care
Authors: Belfer Inna 
Published: May 2014

Spine pain (SP), such as low back pain, is among the most common musculoskeletal disorders and is the single most common disorder causing disability in industrialized countries.1 This pain is typically recurrent; 24 to 87% of individuals who have an episode of SP will suffer a recurrence within 1 year.2 The precise causes of SP and its recurrence are poorly understood due to the heterogenic nature of SP and variety of etiological factors including spine injury, herniated disc, spinal stenosis, osteoarthritis (spondylolysis), fractures (osteomyelitis), deformities, scoliosis, ankylosing spondylitis, bacterial infection, and tumor.3 Physical findings and structural spine abnormalities do not always reflect patient-reported symptoms.4 The relationship between spine degeneration and SP is complex and needs more investigation. Psychosocial risk factors have consistently emerged as predictors of the course of SP.5 Unfortunately, results of treatment interventions targeting these risk factors have yielded mixed picture suggesting that there may be other important factors that have not been examined. Genetic approach may reveal hidden mechanisms underlying interindividual variability in SP phenotypes within the same etiology.6

Recently, several genetic factors have been identified contributing to SP phenotypes and may serve as potential pharmaceutical targets. For example, common polymorphism in SCN9A, a gene encoding Nav1.7 channel, was associated with higher pain postdiscectomy.7 Similarly, common allele in KCNS1 gene encoding for potassium channel subunit, were associated with pain severity in two different SP cohorts.8 Therefore, manipulating these genes/alleles or modifying factors that interact with their effects on pain may lead to pain relief in patients with risk genotypes. Other genes may “protect” from SP, such as GCH1, a gene encoding GTP cyclohydrolase, a key enzyme for catecholamine, serotonin, and nitric oxide production.9 Patients carrying two copies of “protective” allele may have better outcomes from spinal surgery in terms of chronic pain and functioning, so for them it becomes the treatment of choice.

Genetic approaches applied to SP research may help identify important molecular factors that may contribute to the risk for or protection against chronicity and recurrence. It is highly likely that the interactions among genes, psychosocial and psychophysical factors will shape SP experience.10 Findings from human genetic association studies in painful conditions including SP and DDD have important clinical relevance and will eventually lead to personalized spine care. These will include “genetic signatures” of the risk for severe pain or pain chronification as well as patient's response to pain medicine.

Disclosure of Interest

None declared

References

Volinn E. The epidemiology of low back pain in the rest of the world. A review of surveys in low- and middle-income countries. Spine 1997;22(15):1747–1754

Dagenais S, Caro J, Haldeman S. A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J 2008;8(1):8–20

Kent PM, Keating JL. The epidemiology of low back pain in primary care. Chiropr Osteopat 2005;13:13

Hoy D, Brooks P, Blyth F, Buchbinder R. The Epidemiology of low back pain. Best Pract Res Clin Rheumatol 2010;24(6):769–781

Feyer AM, Herbison P, Williamson AM, et al. The role of physical and psychological factors in occupational low back pain: a prospective cohort study. Occup Environ Med 2000;57(2):116–120

Young EE, Lariviere WR, Belfer I. Genetic basis of pain variability: recent advances. J Med Genet 2012;49(1):1–9

Reimann F, Cox JJ, Belfer I, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A 2010;107(11):5148–5153

Costigan M, Belfer I, Griffin RS, et al. Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1. Brain 2010;133(9):2519–2527

Tegeder I, Costigan M, Griffin RS, et al. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006;12(11):1269–1277

Belfer I. Nature and nurture of human pain. Scientifica 2013;2013:415279