Sickle Cell Disease Pain Outcomes Likely Not Related to AVPR1A Genotype

The arginine vasopressin receptor 1a (AVPR1A) single nucleotide polymorphism rs10877969 was not found to influence pain in sickle cell disease.

A study published in Frontiers in Pain Research did not confirm previous findings that suggested a single nucleotide polymorphism (SNP) in arginine vasopressin receptor 1a (AVPR1A) was involved in acute pain and stress-related pain among individuals with sickle cell disease.

Investigators from the University of Florida sourced data from a previously published study about sickle cell disease. Adult patients (N=150) had confirmed sickle cell disease and chronic pain associated with sickle cell disease. They provided blood samples, underwent Quantitative Sensory Testing (QST), and completed the PAINReportIt and Perceived Stress Questionnaire (PSQ) instruments, the latter of which captures stressful feelings on a scale of 0 to 1. The relationship between AVPR1A genotype and pain outcomes was evaluated using linear regression analysis.

The median age of patients was 33.5 (interquartile range [IQR], 26.25-44.00) years, 62.67% were women, 97.33% were Black, 70.67% had hemoglobin type SS, and 44.67% were heterozygous at the AVPR1A SNP rs10877969.

On average, the pain intensity score was 4.39 points, the cold pain threshold was 25.38°C, the heat pain threshold was 38.53°C, the pressure pain threshold was 11.87 g of force, and the PSQ score was 0.37 points.

Although none of the associations were significant, the trend toward a protective T allele effect on pain in SCD warrants future exploration of this SNP/gene in SCD.

No association was observed between rs10877969 genotypes and mechanical pain thresholds (P =.33), perceived stressful life events (P =.51), or average pain intensity (P =.09). Neither gender nor age significantly contributed to the relationship between pain outcomes and AVPR1A genotype.

As the association between genotype and clinical pain trended toward significance, the investigators noted that individuals who were homozygous for TT at rs10877969 tended to report lower pain intensity scores (mean, 3.85 points) compared with those who were heterozygous (mean, 4.48 points) or homozygous for CC (mean, 4.76 points).

No significant interactions between average pain intensity and PSQ score were observed; however, a correlation was identified between clinical pain and environmental stress (r, 0.18; P =.024).

A potential limitation of this study is that the pain instruments used in this study may not have captured the effect of the AVPR1A genotype on pain.

Study authors conclude, “Although none of the associations were significant, the trend toward a protective T allele effect on pain in SCD warrants future exploration of this SNP/gene in SCD. […] As this SNP is located in the promoter region of the gene, further research is warranted to examine the functional impact of this polymorphism on gene transcription and protein production, to understand underlying biological impact.”


Powell-Roach KL, Yao Y, Cao X, et al. Analysis of AVPR1A, thermal and pressure pain thresholds, and stress in sickle cell disease. Front Pain Res. Published online January 4, 2023. doi:10.3389/fpain.2022.1060245