Changes in mu opioid receptors and rheological properties of erythrocytes among opioid abusers

Abstract

Opioids, reported originally to bind to specific receptors in the brain, now also appear to bind to receptors on blood cells. The high prevalence of anemia among chronic opioid users leads us to propose that chronic opiate use results in elevated mu opioid receptor levels on human erythrocytes and that these receptor changes may affect erythrocyte membrane properties. Blood samples from 17 opioid-dependent subjects (based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or DSM-IV) and 15 drug-free controls were assayed for mu opioid receptors on erythrocytes using a flow cytometry immunoassay. Deformability and the hydration status of erythrocytes were studied by ektacytometry. Data were analyzed by independent t-tests, tests of correlation, chi square and cluster analyses. As expected, the percentage of erythrocytes from opioid-dependent subjects with opioid receptors (opioid receptor levels) was significantly higher (47.4 +/- 38.3%) than controls (22.8 +/- 30.1%) (t = 2.01, df = 30, p < 0.05). Also, the opioid-dependent patients showed a wide variation in the percentage of erythrocytes bearing opioid receptors and data analyses of these patients showed two strongly defined clusters. One subgroup consisted of nine individuals with very high receptor levels (mean = 81.5%) while the other had eight patients with low receptor levels (mean = 9.1%) that were not significantly different than the receptor levels of controls. Ektacytometry of opioid dependent patients with high opioid receptor levels showed changes in rheological parameters of erythrocytes, such as deformability index and cellular hydration. For example, a positive correlation was observed between opioid receptor levels and deformability indices among opioid-dependent patients (r = 0.74, p < 0.005). Our findings indicate that the mu opioid receptor is present on human erythrocytes, although with considerable variation in receptor levels, and that the levels of this receptor are significantly elevated with chronic opioid exposure. Moreover, erythrocytes with high opioid receptor levels from chronic opiate users seem to have high deformability. This study may offer clues to the biological properties of peripheral blood cells that may be mediated by mu opioid receptors and lead to a better understanding of some of the clinical effects of opioid use.

Hemorheological changes and characteristic parameters derived from whole blood viscometry in chronic heroin addicts

“…Moreover, they suppose that erythrocytes with high opioid receptor levels from chronic opiate users seem to have high deformability. Our findings from high shear rate viscometry in chronic heroin addicts do not confirm the results of Zeiger et al [10] for higher deformability of red blood cells.…”

“…The same authors suggest that morphine affects the rat red cell membrane directly, rather than through opioids-receptors. Ectacytometry of opioid dependent patients with high opioid receptor levels show changes in rheological parameters of erythrocytes such as deformability index and cellular hydration [10]. A positive correlation between opioid receptor levels and deformability indices among opioid dependent patients (r = 0.74, p < 0.05) was observed by the same authors.…”

Morphine for the Treatment of Pain in Sickle Cell Disease

“…Complementary to these in vitro and experimental observations, opioid drugs have been shown to influence whole blood rheology and cause morphometric and hematometric alterations in erythrocytes in drug users [ 94 ], including high incidence of anemia amongst heroin users [ 95 ]. MOR is expressed on human RBCs and its expression is increased in chronic opioid users [ 96 ]. In this study, RBCs with increased MOR expression also showed higher deformability indices and dehydration.…”

The association of codeine, macrocytosis and bilateral sudden or rapidly progressive profound sensorineural deafness

“…However, it has been associated with both peripheral vascular disease and homocysteine, a well-recognized vascular toxin [10,11]. Opiates have been shown to affect erythrocytes directly in some patients, leading to abnormal deformability, a factor that can influence blood flow [12]. The cochlea is exquisitely sensitive to blood flow, more so than the vestibule [13], and the good implant outcomes in our patients combined with normal vestibular function tests suggest an isolated cochlear pathology.…”