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Genetics can double chance of timely recover from nerve root injury

PainSci » bibliography » Costigan et al 2010
Tags: etiology, genetics, chronic pain, back pain, pro, pain problems, spine

Five articles on PainSci cite Costigan 2010: 1. The Complete Guide to Trigger Points & Myofascial Pain2. A Guide to Sciatica Treatment for Patients3. Complete Guide to Low Back Pain4. The Complete Guide to Neck Pain & Cricks5. Sensitization in Chronic Pain

PainSci notes on Costigan 2010:

Mark your calendars: 2010 was the year researchers confirmed a gene as “one of the first prognostic indicators of chronic pain risk,” doubling or tripling the odds that a low back pain patient will recover in a timely fashion from nerve root injury. Screening for this gene is not yet something that is clinically available, but it probably will be someday, and then you will know: the universe really does hate you.

original abstract Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To define such factors further, we performed a large-scale gene profiling experiment which plotted global expression changes in the rat dorsal root ganglion in three peripheral neuropathic pain models. This resulted in the discovery that the potassium channel alpha subunit KCNS1, involved in neuronal excitability, is constitutively expressed in sensory neurons and markedly downregulated following nerve injury. KCNS1 was then characterized by an unbiased network analysis as a putative pain gene, a result confirmed by single nucleotide polymorphism association studies in humans. A common amino acid changing allele, the 'valine risk allele', was significantly associated with higher pain scores in five of six independent patient cohorts assayed (total of 1359 subjects). Risk allele prevalence is high, with 18-22% of the population homozygous, and an additional 50% heterozygous. At lower levels of nerve damage (lumbar back pain with disc herniation) association with greater pain outcome in homozygote patients is P = 0.003, increasing to P = 0.0001 for higher levels of nerve injury (limb amputation). The combined P-value for pain association in all six cohorts tested is 1.14 E-08. The risk profile of this marker is additive: two copies confer the most, one intermediate and none the least risk. Relative degrees of enhanced risk vary between cohorts, but for patients with lumbar back pain, they range between 2- and 3-fold. Although work still remains to define the potential role of this protein in the pathogenic process, here we present the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk. Screening for this allele could help define those individuals prone to a transition to persistent pain, and thus requiring therapeutic strategies or lifestyle changes that minimize nerve injury.

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