μ-Opioid Receptor Gene A118 G Variants and Persistent Pain Symptoms Among Men and Women Experiencing Motor Vehicle Collision

Linnstaedt, Sarah D.; Hu, Jun; Bortsov, Andrey V.; Soward, April C.; Swor, Robert A.; Jones, J. Stephen; Lee, David; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; Hendry, Phyllis L.; McLean, Samuel A.

doi:10.1016/j.jpain.2015.03.011

Cited by 22 publications

(21 citation statements)

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“…Associations between polymorphisms in CRHBP, CRHR1 and NR3C1 and overall pain intensity in the past week, at 6 weeks, 6 months, and 1 year were assessed using a repeated measures mixed model. Based on the results of previous studies[9; 10; 30; 36], study site, sex, past pain severity, and time from trauma in weeks were included in the model as covariates. Multiple testing was controlled for using the method of principal components[39].…”

Section: Methodsmentioning

confidence: 99%

CRHBP polymorphisms predict chronic pain development following motor vehicle collision

Linnstaedt

Bortsov

Soward

et al. 2016

Pain

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Musculoskeletal pain (MSP) is a common sequela of traumatic stress exposure. While biologic factors contributing to chronic MSP after motor vehicle collision (MVC) have traditionally focused on tissue injury, increasing evidence suggests that neuro/stress/immune processes mediated by stress system activation may play a more dominant role. In a previous study we found that genetic variants in the hypothalamic-pituitary-adrenal (HPA) axis-related gene FKBP5 influence vulnerability to persistent MSP 6 weeks after MVC. In the present cohort study (n = 855) we evaluated whether genetic variants in several other important HPA axis-related genes, including the glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor R1 (CRHR1), and corticotropin-releasing hormone binding protein (CRHBP), influence risk of chronic MSP over time after MVC. Genetic polymorphism rs7718461 in the CRHBP gene showed significant association (p=0.0012) with overall pain severity during the year after MVC in regression models controlling for multiple comparisons. Two additional CRHBP alleles in high Linkage Disequilibrium with rs7718461 also showed trend-level significance. In secondary analyses, a significant interaction between this CRHBP locus (Minor Allele Frequency = 0.33) and time was observed (p = 0.015), with increasing effect observed over time following trauma. A significant CRHBP*FKBP5 interaction was also observed, with substantially increased MSP after MVC in those with a risk allele in both genes compared to either gene alone. The results of this study indicate that genetic variants in two different HPA axis genes predict chronic MSP severity following MVC, and support the hypothesis that the HPA axis is involved in chronic post-MVC MSP pathogenesis.

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Section: Methodsmentioning

confidence: 99%

CRHBP polymorphisms predict chronic pain development following motor vehicle collision

Linnstaedt

Bortsov

Soward

et al. 2016

Pain

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“…This information could be used to guide leveling criteria or operative treatment decisions. Linnstaedt et al 37 Pain Genetic association study Patients with an AG or GG genotype at the OPRM1 A118G allele have less severe pain at 6 weeks after trauma.…”

Section: Direct-to-consumer Testsmentioning

confidence: 99%

Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

Monte

Kabrhel

Puskarich

et al. 2016

Academic Emergency Medicine

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Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department. While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the emergency department will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end users.

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“…This proposed altering the transition from acute to chronic pain (ATTAC pain) study will help address this critical need by evaluating the preliminary tolerability and effectiveness of a non-opioid, duloxetine—a serotonin-norepinephrine reuptake inhibitor (SNRI) marketed for the treatment of generalised anxiety disorder, major depressive disorder and chronic pain. Evidence suggests that stress systems and their interactions with neurological and immune systems play an influential role in persistent and chronic musculoskeletal pain development; serotonin and norepinephrine are important neurotransmitters in this regard 11 12. The ATTAC pain study will examine whether duloxetine can reduce acute and persistent musculoskeletal pain among adults presenting to the ED with either traumatic or atraumatic (eg, lifting injury) acute musculoskeletal pain.…”

Section: Introductionmentioning

confidence: 99%

Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain)

et al. 2019

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IntroductionChronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.Methods and analysisThe primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18–59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.Ethics and disseminationEthics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.Trial registration numberNCT03315533.

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μ-Opioid Receptor Gene A118 G Variants and Persistent Pain Symptoms Among Men and Women Experiencing Motor Vehicle Collision

Cited by 22 publications

References 50 publications

CRHBP polymorphisms predict chronic pain development following motor vehicle collision

CRHBP polymorphisms predict chronic pain development following motor vehicle collision

Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain)

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