Pain Intensity the First Year after Lumbar Disc Herniation Is Associated with the A118G Polymorphism in the Opioid Receptor Mu 1 Gene: Evidence of a Sex and Genotype Interaction

Abstract

Earlier studies have shown that the single nucleotide polymorphism (SNP) A118G (rs1799971) in the opioid receptor mu 1 (OPRM1) gene may affect pain sensitivity. In the present study we investigated whether the A118G SNP could predict clinical outcome regarding progression of pain intensity and disability in patients with low back pain and sciatica after lumbar disc herniation. Patients (n ϭ 258) with lumbar disc herniation and sciatic pain, all European-Caucasian, were recruited from two hospitals in Norway. Pain and disability were rated on a visual analog scale (VAS), by McGill Sensory Questionnaire and by Oswestry Disability Index (ODI) over a 12 months period. The data revealed a significant interaction between sex and A118G genotype regarding the pain intensity during the 12 months (VAS, p ϭ 0.002; McGill, p ϭ 0.021; ODI, p ϭ 0.205, repeated-measures ANOVA). We found that */G women had a slower recovery rate than the */G men. Actually, the */G women had 2.3 times as much pain as the */G men 12 months after the disc herniation (VAS, p ϭ 0.043, one-way ANOVA; p ϭ 0.035, Tukey HSD). In contrast, the A/A women and A/A men seemed to have almost exactly the same recovery rate. The present data suggest that OPRM1 G allele increases the pain intensity in women, but has a protective effect in men the first year after disc herniation.

Research design considerations for chronic pain prevention clinical trials

“…Regarding COMT , polymorphisms and haplotypes have been associated with laboratory pain sensitivity, and acute and chronic clinical pain [13,40], including long-term outcomes after back surgery [143]. Similarly, the A118G polymorphism of OPRM1 has been associated with experimental pain sensitivity and with clinical pain [53,71,123], including long-term outcomes of acute back pain [124]. Finally, GCH1 genotypes have been associated with experimental and clinical pain responses across several cohorts [15,28,159,160], and GCH1 genotypes have predicted outcomes from lumbar spine surgery [96,160].…”

“…For example, previous studies have reported that COMT, OPRM1 , and GCH1 show sex-specific associations with pain responses [14,15,124]. In addition, COMT haplotypes have been shown to interact with psychological functioning (i.e., pain catastrophizing) to predict both experimental and clinical shoulder pain outcomes [58,60].…”

Failed back surgery syndrome: Who has failed?

“…In a twin study of low back pain comparing 2108 mono-and dizygotic twins suggested that a small genetic contributor might play a role in men but not in women. A study of 258 patients with lumbar disc herniation suggested that the A118G gene might play a role in postoperative pain [24].…”

Pain in women

“…[11] Moreover, a recent study in patients with low back pain and sciatica after lumbar disc herniation found that this same allele increased twice the pain intensity in women compared to men. [12] Thus, human pain genes may have sex-biased effects affecting both sexes but to different degrees; sex-specific effects affecting only one but not another sex; and sex-antagonistic effects affecting both sexes but in opposite directions.…”