Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States

Abstract. Introduction:. Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP. Objectives:. We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data. Methods:. A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP. Results:. Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year. Conclusion:. Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy

Loss of feedback inhibition via D2 autoreceptors enhances acquisition of cocaine taking and reactivity to drug-paired cues.

A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse

Loss of feedback inhibition via D2 autoreceptors enhances acquisition of cocaine taking and reactivity to drug-paired cues

A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse.Fil: Holroyd, Kathryn B.. Public Health Service. National Institute Of Health; Estados UnidosFil: Adrover, Martín Federico. Public Health Service. National Institute Of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fuino, Robert L.. Public Health Service. National Institute Of Health; Estados UnidosFil: Bock, Roland. Public Health Service. National Institute Of Health; Estados UnidosFil: Kaplan, Alanna R.. Public Health Service. National Institute Of Health; Estados UnidosFil: Gremel, Christina M.. Public Health Service. National Institute Of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Alvarez, Veronica. Public Health Service. National Institute Of Health; Estados Unido