Three major haplotypes of the β₂ adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder

Abstract

Adrenergic receptor β 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.

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

“…We previously identified polymorphisms in the COMT gene that are associated with low COMT enzymatic activity and TMJD onset (Diatchenko et al 2005). Here, we report the mechanism whereby low levels of COMT lead to exacerbated pain states.…”

“…Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint Disorder (TMJD) and are associated with heightened experimental pain sensitivity (Diatchenko et al 2005). Variants associated with heightened pain sensitivity produce lower COMT activity.…”

“…Facial pain patients exhibit lower COMT activity relative to controls (Marbach and Levitt 1976). Furthermore, functional polymorphisms in the COMT gene resulting in 3-to 15-fold reductions in COMT activity (Lotta et al 1995;Nackley et al 2005a) are associated with fibromyalgia (Gursoy et al 2003), TMJD onset (Diatchenko et al 2005), experimental pain sensitivity (Diatchenko et al 2005;Zubieta et al 2003), and morphine efficacy in cancer pain treatment (Rakvag et al 2005). Collectively, these results suggest that elevated catecholamime levels promote persistent pain states.…”

Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains

“…In their heuristic model, haplotype 2 is related to high expression of ␤ 2 -AR in the synaptic cleft and to inefficient internalization of such receptors in response to agonist stimulation. Their longitudinal observation demonstrated that healthy women with this haplotype 2 have a higher risk of developing TMJ syndrome (12).…”

Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction

“…While exposure to bullying in the workplace is a risk factor for pain (10,11), pain may also be determined by the individuals psychological profile and genetic susceptibility (12). Interestingly, as much as 60% (range 25-60%) of the variance in experimental pain may be explained by genetic variability (13).…”