Standing on the shoulders of bias: lack of transparency and reporting of critical rigor characteristics in pain research

Abstract

Rigorous experimental design with transparent reporting in biomedical science reduces risk of bias and allows for scientists to judge the quality of the research. Basic factors of rigor such as blinding, randomization, power analysis, and inclusion of both sexes impact the reproducibility by reducing experimental bias. We designed a systematic study to analyze basic factors of rigor, inclusion of sex, and whether data were analyzed or disaggregated by sex over the past 10 years in the journal PAIN. Studies that included humans reported randomization in 81%, blinding in 48%, and the use of a power analysis calculation in 27% over the past 10 years. Studies that included mice reported randomization in 35%, blinding in 70%, and the use of a power analysis in 9%. Studies that included rats reported randomization in 38%, blinding in 63%, and the use of power analysis in 12%. This study also found that human studies consistently included both sexes over the past decade, but less than 20% of data were disaggregated or analyzed for sex differences. Although mouse and rat studies predominately used males only, there has been a slight increase in inclusion of both sexes over the past few years. Justification for single-sex studies was below 50% in both human and rodent data. In both human and animal studies, transparency in reporting of experimental design and inclusion of both sexes should be considered standard practice and will result in improved quality and reproducibility of published research.

Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice

“…There are significant sex differences in the generation of pain, however, previous mouse and rat studies have predominately used males only [76]. Gonadectomized and gonadal hormone replacement alter the response of BDNF and the activity-induced pain model [67, 77].…”

Influence of routine exercise on the peripheral immune system to prevent and alleviate pain

“…Also worth noting is the lack of research utilizing both sexes to study the effectiveness and mechanisms of exercise-induced analgesia. This is especially concerning in studies exploring the immune system since there are significant sex differences in immune mechanisms in the generation of pain ( Baskozos et al, 2019 , Cowie et al, 2019 , Mecklenburg et al, 2022 , Mogil, 2020 , Plumb et al, 2023 , Sorge et al, 2015 ). Of the papers that did include both males and females, sex differences were found in exercise immune mechanisms ( Mifflin et al, 2019 , Lesnak et al, 2022 ) and are highlighted above.…”

Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome

“…Lastly, due to the heterogeneity of the patient characteristics used in each study, we were unable to draw any conclusions regarding potential impact of sex or disease severity on the ligandreceptor interactome. Future work aimed at underpinning the molecular mechanisms of PASC associated pain should power their studies to be able to explore for sex differences as the immune system's mechanistic role in producing pain has been demonstrated to be sex dimorphic [149][150][151][152][153][154].…”