Pain Experiences and Their Relation to Opioid Misuse Risk and Emotion Dysregulation

Pain is a complex, multidimensional experience but often is measured as a unidimensional experience. This study aimed to separately assess the sensory and affective components of pain and identify their relations to important pain-related outcomes, particularly in terms of opioid misuse risk and emotion dysregulation among patients with chronic pain receiving treatment in Appalachia. Two hundred and twelve patients presenting to a multidisciplinary pain center completed the Difficulties in Emotion Regulation Scale (DERS-18), Screener and Opioid Assessment for Patients with Pain—Revised (SOAPP-R), and short-form McGill Pain Questionnaire (SF-MPQ). The sensory experience of pain was unrelated to emotion dysregulation (r = 0.06, p = 0.57) and weakly related to opioid misuse risk (r = 0.182, p \u3c 0.05). In contrast, the affective experience of pain was moderately related to emotion dysregulation (r = 0.217, p \u3c 0.05) and strongly related to opioid misuse risk (r = 0.37, p \u3c 0.01). In addition, emotion dysregulation predicted variance in opioid misuse risk above and beyond the affective and sensory experiences of pain ((b = 0.693, p \u3c 0.001). The results suggest patients with a strong affective experience versus sensory experience of pain and challenges with emotion regulation may require a more comprehensive intervention to address these underlying components in order to reduce their risk of misusing opioid medications

Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys and Gly

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3000494Glutathione thiyl radicals (GS•) were generated in H2O and D2O by either exposure of GSH to AAPH#, photoirradiation of GSH in the presence of acetone, or photoirradiation of GSSG. Detailed interpretation of the fragmentation pathways of deuterated GSH and GSH-derivatives during mass spectrometry analysis allowed us to demonstrate that reversible intramolecular H-atom transfer reactions between GS• and C-H bonds at Cys[αC], Cys[βC], and Gly[αC] are possible

Pain Experiences and Their Relation to Opioid Misuse Risk and Emotion Dysregulation

Pain is a complex, multidimensional experience but often is measured as a unidimensional experience. This study aimed to separately assess the sensory and affective components of pain and identify their relations to important pain-related outcomes, particularly in terms of opioid misuse risk and emotion dysregulation among patients with chronic pain receiving treatment in Appalachia. Two hundred and twelve patients presenting to a multidisciplinary pain center completed the Difficulties in Emotion Regulation Scale (DERS-18), Screener and Opioid Assessment for Patients with Pain—Revised (SOAPP-R), and short-form McGill Pain Questionnaire (SF-MPQ). The sensory experience of pain was unrelated to emotion dysregulation (r = 0.06, p=0.57) and weakly related to opioid misuse risk (r = 0.182, p<0.05). In contrast, the affective experience of pain was moderately related to emotion dysregulation (r = 0.217, p<0.05) and strongly related to opioid misuse risk (r = 0.37, p<0.01). In addition, emotion dysregulation predicted variance in opioid misuse risk above and beyond the affective and sensory experiences of pain ((b = 0.693, p<0.001). The results suggest patients with a strong affective experience versus sensory experience of pain and challenges with emotion regulation may require a more comprehensive intervention to address these underlying components in order to reduce their risk of misusing opioid medications

Isotope effects and intermediates in the reduction of NO by P450NOR

The mechanism of the heme-thiolate-dependent NADH-NO reductase (P450NOR) from Fusarium oxysporum was investigated by kinetic isotope effects including protio, [4S-2H]-, [4R-2H]-, [4,42H2]-NADH and stopped-flow measurements. The respective kinetic isotope effects were measured at high NO concentrations and were found to be 1.7, 2.3 and 3.8 indicating a rate-limitation at the reduction step and a moderate stereoselectivity in binding of the cofactor NADH. In a different approach the kinetic isotope effects were determined directly for the reaction of the FeIII–NO complex with [4R-2H]- and [4S-2H]-NADH by stopped-flow spectroscopy. The resulting isotope effects were 2.7±0.4 for the R-form and 1.1±0.1 for the S-form. In addition the 444 nm intermediate could be chemically generated by addition of an ethanolic borohydride solution to the ferric–NO complex at -10°C. In pulse radiolysis experiments a similar absorbing species could be observed when hydroxylamine radicals were generated in the presence of Fe (III) P450NOR. Based on these results we postulate hydride transfer from NADH to the ferric P450–NO complex resulting in a ferric hydroxylamine-radical or ferryl hydroxylamine-complex and this step, as indicated by the kinetic isotope effects, to be rate-limiting at high concentrations of NO. However, at low concentrations of NO the decay of the 444 nm species becomes the rate-limiting step as envisaged by stopped-flow and optical kinetic measurements in a system in which NO was continuously generated. The last step in the catalytic cycle may proceed by a direct addition of the NO radical to the Fe–hydroxylamine complex or by electron transfer from the NO radical to the ferric–thiyl moiety in analogy to the postulated mechanisms of prostacyclin and thromboxane biosynthesis by the corresponding P450 enzymes. The latter process of electron transfer could then constitute a common step in all heme-thiolate catalyzed reactions

Isotope effects and intermediates in the reduction of NO by P450NOR

The mechanism of the heme-thiolate-dependent NADH-NO reductase (P450NOR) from Fusarium oxysporum was investigated by kinetic isotope effects including protio, [4S-2H]-, [4R-2H]-, [4,42H2]-NADH and stopped-flow measurements. The respective kinetic isotope effects were measured at high NO concentrations and were found to be 1.7, 2.3 and 3.8 indicating a rate-limitation at the reduction step and a moderate stereoselectivity in binding of the cofactor NADH. In a different approach the kinetic isotope effects were determined directly for the reaction of the FeIII–NO complex with [4R-2H]- and [4S-2H]-NADH by stopped-flow spectroscopy. The resulting isotope effects were 2.7±0.4 for the R-form and 1.1±0.1 for the S-form. In addition the 444 nm intermediate could be chemically generated by addition of an ethanolic borohydride solution to the ferric–NO complex at -10°C. In pulse radiolysis experiments a similar absorbing species could be observed when hydroxylamine radicals were generated in the presence of Fe (III) P450NOR. Based on these results we postulate hydride transfer from NADH to the ferric P450–NO complex resulting in a ferric hydroxylamine-radical or ferryl hydroxylamine-complex and this step, as indicated by the kinetic isotope effects, to be rate-limiting at high concentrations of NO. However, at low concentrations of NO the decay of the 444 nm species becomes the rate-limiting step as envisaged by stopped-flow and optical kinetic measurements in a system in which NO was continuously generated. The last step in the catalytic cycle may proceed by a direct addition of the NO radical to the Fe–hydroxylamine complex or by electron transfer from the NO radical to the ferric–thiyl moiety in analogy to the postulated mechanisms of prostacyclin and thromboxane biosynthesis by the corresponding P450 enzymes. The latter process of electron transfer could then constitute a common step in all heme-thiolate catalyzed reactions

Structure and Enzymatic Properties of Molecular Dendronized Polymer−Enzyme Conjugates and Their Entrapment inside Giant Vesicles. Langmuir

Macromolecular hybrid structures were prepared in which two types of enzymes, horseradish peroxidase (HRP) and bovine erythrocytes Cu,Zn-superoxide dismutase (SOD), were linked to a fluorescently labeled, polycationic, dendronized polymer (denpol). Two homologous denpols of first and second generation were used and compared, and the activities of HRP and SOD of the conjugates were measured in aqueous solution separately and in combination. In the latter case the efficiency of the two enzymes in catalyzing a two-step cascade reaction was evaluated. Both enzymes in the two types of conjugates were highly active and comparable to free enzymes, although the efficiency of the enzymes bound to the second-generation denpol was significantly lower (up to a factor of 2) than the efficiency of HRP and SOD linked to the first-generation denpol. Both conjugates were analyzed by atomic force microscopy (AFM), confirming the expected increase in object size compared to free denpols and demonstrating the presence of enzyme molecules localized along the denpol chains. Finally, giant phospholipid vesicles with diameters of up to about 20 μm containing in their aqueous interior pool a first-generation denpol−HRP conjugate were prepared. The HRP of the entrapped conjugate was shown to remain active toward externally added, membrane-permeable substrates, an important prerequisite for the development of vesicular multienzyme reaction systems