Contribution of COMT and BDNF Genotype and Expression to the Risk of Transition From Acute to Chronic Low Back Pain

Abstract

Objectives: A number of factors, including heritability and the environment, contribute to risk of transition from acute low back pain to chronic low back pain (CLBP). The aim of this study was to (1) compare somatosensory function and pain ratings at low back pain (LBP) onset between the acute low back pain and CLBP conditions and (2) evaluate associations between BDNF and COMT polymorphisms and expression levels at LBP onset to acute and chronic pain burden and risk for transition to the chronic pain state.

Methods: In this longitudinal study, 220 participants were enrolled following recent onset of LBP and data were collected until the LBP resolved or until the end of the study at 6 months. Forty-two participants' pain resolved before 6 weeks from onset and 42 participants continued to have pain at 6 months. Patient-reported pain burden, somatosensory function (quantitative sensory testing), and blood samples were collected at each study visit.

Results: CLBP is associated with greater pain burden and somatosensory hypersensitivity at the time of LBP onset. COMT rs4680 genotype (GG) was associated with acute cold pain sensitivity and with the risk for transition to CLBP while COMT expression was independently associated with risk for transition.

Discussion: CLBP was characterized by higher reported pain burden and augmented hypersensitivity at LBP onset. COMT expression and genotype were associated with acute pain burden and likelihood of transition to CLBP.

FIGURE 1

Pain burden is higher early on for those who will go on to develop chronic low back pain (CLBP) compared with those with acute resolving LBP. Within 2 weeks of LBP onset, those that will develop CLBP score higher on all subscales of the Brief Pain Inventory (BPI) assessed, all P<0.001. *Statistical significance.

FIGURE 2

McGill Pain Questionnaire Present Pain Intensity (VAS) Ratings are higher early on for those who will develop chronic low back pain (CLBP) compared with those with acute resolving LBP. CLBP participants reported higher present pain intensity at the time of recruitment (P<0.001). *Statistical significance. VAS indicates visual analogue scale.

FIGURE 3

Somatosensory function is altered in those who will develop chronic low back pain (CLBP) compared with those with acute resolving LBP. When testing was conducted on the lower back (the painful area), cold pain threshold (CPT, P=0.010; A), mechanical pain threshold (C, P=0.021), and dynamic mechanical allodynia to brush stroke (D, P=0.018) was exacerbated in those that would go on to develop CLBP while pressure pain threshold (PPT, P>0.05; B) did not differ between groups. When testing was conducted on a remote location on the nondominant forearm only CPT (A, P=0.012) and PPT (B, P=0.041) were significantly different between CLBP and acute resolving LBP groups. *Statistical significance.

FIGURE 4

COMT and BDNF SNP genotypes are significantly associated with likelihood of transition to chronic low back pain (CLBP). A, The genotypic frequencies of COMT SNP rs4680 differed significantly between the groups (ALBP and CLBP) (P=0.006) with more participants homozygous for the major allele (Met/Met) found in the CLBP group. B, Fewer subjects in the CLBP group were found to be homozygous for the minor allele at rs6265 BDNF (P=0.009). SNP indicates single nucleotide polymorphism.

FIGURE 5

COMT SNP rs4680 genotype and BDNF SNP rs6525 genotype are significantly associated with cold pain threshold (CPT) at the time of initial recruitment regardless of whether they would go on to resolve quickly or to develop CLBP. A, Participants homozygous for the minor allele (Met/Met) at the COMT SNP rs4680 had increased sensitivity (lower threshold) for cold pain. B, Participants carrying at least 1 minor allele at BDNF rs6525 also exhibited lower CPT thresholds. *Statistical significance.