Background & Aims

There is an increasing need to discover strategies that involve activating patients’ endogenous pain modulation (EPM) systems to better manage chronic pain. Placebo hypoalgesia elicited in a laboratory setting [1-4], can be used as a proxy for EPM. Genetic studies have demonstrated that placebo hypoalgesia relies on single nucleotide polymorphisms of ?-opioid receptor (OPRM1 rs1799971) [5] and of catechol-O-methyltransferase (COMT rs4680) and fatty acid amide hydrolase (FAAH rs324420) [6, 7]. Besides genetic variations, the social disparities specifically the socioeconomic perspective might be relevant in accounting for variability of placebo effects on chronic pain. Currently, there are no studies exploring the association of genetic variants of EPM with a socioeconomic position (SEP) perspective. Thus, this quasi-experimental study aims to compare the influence of genetic variants of EPM and socioeconomic position on variability in placebo hypoalgesia.

Methods

We conducted a quasi-experimental study to examine the moderation of genetic variants and SEP on placebo hypoalgesia. We recruited 369 patients with temporal mandibular disorder (TMD) (285 females) and 366 pain-free healthy controls (HC) (217 females) to complete a placebo experiment using the classical conditioning paradigm [8]. Saliva samples were collected using Oragene-DNA (OGR-500) kits and were genotyped using the Illumina Human OmniExpressexome array. Latent Class analysis was conducted to group participants into distinct SEP using individual markers namely income, education, occupation, and neighborhood marker namely Area Deprivation index (ADI) [9]. Linear mixed model was performed with TMD vs Healthy Controls, SEP latent class, and the three genetic variants as three fixed factors. The interaction was modeled. Age, sex, race, and temperature used during the test phase were controlled as covariates. Bonferroni correction was performed for multiple comparisons.

Results

Both TMD and HC participants had similar placebo hypoalgesia levels (F1,4757.64 = 1.03, p= 0.30). There was a significant main effect (F1,4757.64 = 7.62, p= 0.006) and interaction of SEP, where among TMD patients, those who were SEP distressed had lower placebo hypoalgesia (15.03+/- 1.74) compared to SEP prosperous (19.79 +/- 1.02, F1,4757.64 = 14.67, p<0.001). Among TMD patients with OPRM1 rs1799971 G-carrier, those who were SEP distressed had lower placebo hypoalgesia compared to SEP prosperous (F1,4360.14 = 58.01, p<0.001). Similar results were found among those with OPRM1 rs1799971 AA (F1,4360.14 = 4.36, p=0.03), COMT rs4680 met/met (F1,4350.61 = 10.33, p=0.001), met/val (F1,4350.61 = 4.01, p=0.04), val/val (F1,4350.61 = 13.41, p<0.001) and FAAH rs324420 pro/pro (F1,4359.12 = 20.59, p<0.001). On the contrary placebo hypoalgesia in HC participants did not differ among SEP distressed (20.47+/- 1.10) and SEP prosperous (20.05 +/- 1.30, F1,4757.64 = 0.03, p=0.84).

Conclusions

Our previous research has demonstrated that individuals suffering from TMD exhibit placebo effects of comparable magnitude to those observed in HC [10]. Moreover, we found that race influences magnitude of placebo effects with African American or black having smaller placebo effects than White participants[8]. This study expands on previous findings that indicate that socioeconomic distress may play a role in determining the magnitude of placebo hypoalgesia in participants with chronic pain compared to HC participants. To our knowledge this is the first report of socioeconomic distress impacting the occurrence of placebo effects. The implications of this novel insight into the interplay between socioeconomic factors and placebo-induced pain modulation are substantial, urging further exploration and understanding of these dynamics.

References

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Presenting Author

Nandini Raghuraman

Poster Authors

Nandini Raghuraman

MSc

University of Maryland Baltimore

Lead Author

Yang Wang

School of Nursing, University of Maryland, Baltimore

Lead Author

Susan Dorsey

PhD

University of Maryland Baltimore, School of Nursing

Lead Author

Luana Colloca and PhD

Placebo Beyond Opinions Center, University of Maryland School of Nursing, MD, USA

Lead Author

Topics

  • Genetics