Adrenergic receptor 2 (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic ...variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. These genetic variants should also interact with environmental factors such as physical or emotional stress to produce a phenotype vulnerable to pathological states. In this study, we determined whether common genetic variants of ADRB2 contribute to the development of a common chronic pain condition that is associated with increased levels of psychological distress and low blood pressure, factors which are strongly influenced by the adrenergic system. We genotyped 202 female subjects and examined the relationships between three major ADRB2 haplotypes and psychological factors, resting blood pressure, and the risk of developing a chronic musculoskeletal pain condition-Temporomandibular Joint Disorder (TMD). We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist-induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options.
Letters to the Editor Fillingim, Roger B.; Edwards, Robert R.; Doleys, Daniel M.
The Clinical journal of pain,
03/2002, Letnik:
18, Številka:
2
Journal Article
Doc number: 56 Abstract Background: Nearly one-third of the United States adult population suffers from hypertension. Hydrochlorothiazide (HCTZ), one of the most commonly used medications to treat ...hypertension, has variable efficacy. The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. DOT1L, MLLT3, SIRT1 , and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaCα subunit. This study aimed to determine the role of variation in these regulatory genes on blood pressure response to HCTZ, and secondarily, untreated blood pressure. Methods: We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant. Results: In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed. Conclusions: Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1 , and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.
Presentation 6 Robinson, Michael E.; Brown, Jennifer L.; George, Steven Z. ...
Archives of physical medicine and rehabilitation,
10/2003, Letnik:
84, Številka:
10
Journal Article
ABSTRACT
The acute effects of engaging in challenging mental work during a single session of aerobic exercise were examined on measures of subjective mood and cardiovascular function. Fifty‐seven ...female subjects were randomly assigned to participate in either a 10‐min aerobic exercise condition or a no‐exercise control condition. Half of the subjects in each group performed digits backward problems during this time period, and no mental stressors were presented to the other subjects. The results indicated that the exercise and mental stress conditions had additive effects on subjective anxiety levels and on cardiovascular responses during exercise. Both exercise and mental stress increased heart rate. In addition, exercise had anti‐anxiety and vasodilative effects, but both of these influences were attenuated by opposing main effects for mental stress exposure. No effects were found for exercise on measures of cardiovascular reactivity to a later digits backward stressor. The results are consistent with previous research in suggesting that exposure to mental stressors during aerobic exercise provides no acute psychological benefits but attenuates some of the mood improvements and vasodilative effects of the exercise activity.
Cognitive-behavioral interventions have gained wide acceptance as effective treatments for reducing distress and disability among persons with chronic pain. Although cognitive and behavioral ...theories, and their subsequent applications, were initially developed in independent academic camps, they have been woven together effectively in the field of chronic pain. Research supports clinicians' perceptions of the efficacy of these interventions applied within comprehensive treatment programs. Evidence for their cost-efficiency or cost-offset potential is scant, however. Existing data suggest that outpatient programs incorporating cognitive-behavioral interventions are effective, but further cost and outcome data are needed to convince health care purchasers of the value of these interventions. Research, in cooperation with insurers, to develop outcome indices incorporating cost and quality of life is most needed. Longitudinal studies to document the potential economic value of pain treatment incorporating cognitive-behavioral interventions should be the major focus of future research.
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