Regional Mu Opioid Receptor Regulation of Sensory and Affective Dimensions of Pain

Zubieta, Jon-Kar; Smith, Yolanda R.; Bueller, Joshua A.; Xu, Yanjun; Kilbourn, Michael R.; Jewett, Douglas M.; Meyer, Charles R.; Koeppe, Robert A.; Stohler, Christian S.

doi:10.1126/science.1060952

Cited by 759 publications

(630 citation statements)

References 48 publications

Supporting

Mentioning

564

Contrasting

Unclassified

Order By: Relevance

“…In particular, opioid release in cortical regions involved in emotional processing appears to suppress the emotive element of pain (Zubieta et al, 2001) and affective states such as sadness (Zubieta et al, 2003), whereas blocking µ-opioid receptors with naloxone increases activity in these regions (Borras et al, 2004). Thus, activation of the endogenous opioid system during psychological stress could suppress the affective and sensory components of pain independently.…”

Section: Introductionmentioning

confidence: 99%

Negative affect, pain and sex: The role of endogenous opioids

Frew

Drummond

2007

Pain

View full text Add to dashboard Cite

Opioid neurotransmission modulates pain and negative affect during psychological stress.To determine whether these effects differ between men and women, the opioid receptor antagonist naltrexone or placebo was administered double-blind to 21 men and 22 women before they completed 30 minutes of difficult mental arithmetic. To heighten negative affect, participants received seven moderately noxious electric shocks during the math task, which were believed to be contingent upon performance. Before and after the math task, participants rated pain intensity and unpleasantness while their left hand was immersed in 2 o C water for up to 4 minutes. Anxiety, discouragement and anger were also rated before, during and after the math task. Tolerance of cold-induced pain was greater in men, whereas discouragement during the math task was greater in women. Opioid blockade did not influence ratings of negative affect, which increased in line with the intensity and unpleasantness of shock-induced pain. The intensity and unpleasantness of cold-induced pain increased after the math task only in women administered naltrexone.Within the naltrexone condition, pain ratings increased most in the most discouraged subjects. However, this relationship was absent in placebo recipients, implying that the hyperalgesic effect of psychological distress was tempered by opioid release. Greater stress-evoked discouragement in women than men may explain why cold-induced pain increased after the math task only in women administered naltrexone.

show abstract

Section: Introductionmentioning

confidence: 99%

Negative affect, pain and sex: The role of endogenous opioids

Frew

Drummond

2007

Pain

View full text Add to dashboard Cite

show abstract

“…This physical and emotional stress activates endogenous opioid neurotransmission in regions of the brain that regulate pain, stress and emotion 20,21 . Endogenous opioid release suppresses pain, stress and anxiety-like responses in animal models 22,23 and humans 21 . The behavioural effects of NPY are mediated, at least in part, through interactions with the endogenous opioid system 24,25 .…”

mentioning

confidence: 99%

Genetic variation in human NPY expression affects stress response and emotion

Zhou

Zhu

Hariri

et al. 2008

Nature

Self Cite

384

363

View full text Add to dashboard Cite

Understanding inter-individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y (NPY) is anxiolytic 1,2 and its release is induced by stress 3 . NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories [4][5][6] . Here we show that haplotype-driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in postmortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype-driven NPY expression predicted higher emotion-induced activation of the amygdala, as well as diminished resiliency as assessed by pain/stress-induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter-individual variation in resiliency to stress, a risk factor for many diseases.Reprints and permissions information is available at www.nature.com/reprints. Correspondence and requests for materials should be addressed to D.G. (E-mail: davidgoldman@mail.nih.gov). * These authors contributed equally to this work. † Present address: Innovation Centre China, AstraZeneca Global R&D, Shanghai 201203, China. Supplementary Fig. 1b). Five haplotypes (H1-H5) account for 93.8% of chromosomes in this block (Fig. 1a).We observed haplotype-driven NPY mRNA expression in postmortem brain (US Caucasians, Miami sample) by detecting the differential expression of alleles at single nucleotide polymorphism (SNP) rs5574 C/T, selected because of its high frequency and location in the transcript. Of these 28 samples, chosen because all were heterozygous for rs5574, 16 (57%) showed differential allele expression at an allele ratio of more than 1.2, in either direction. H1 and H4 were low-expression haplotypes, H2 was high, H3 was intermediate and H5 was unclassified because only two H1/H5 heterozygous brains were available (Fig. 1b). This expression-based functional classification is consistent with a cladistically based clustering of haplotypes, indicating that expression variation is linked to gene ancestry (Fig. 1a). The effects on expression of the more common H1, H2 and H3 haplotypes were verified in 47 lymphoblastoid cell lines derived from healthy Finnish men ( Fig. 1c) representing the six common diplotypes (72% of all diplotypes). On the basis of lymphoblast NPY mRNA levels, the expression value for each haplotype was calculated by regression analysis. Expression values for the six common diplotypes were well predicted under a co...

show abstract

“…[ 11 C]Carfentanil is a selective mu opioid receptor radiotracer (Titeler et al, 1989) which labels mu opioid receptors in both proopiomelanocortin (POMC)/beta endorphin pathways (hypothalamus, nucleus accumbens, medial thalamus), as well as in enkephalinergic pathways (striatopallidal pathway). It is sensitive to changes in endogenous opioid activity (Bencherif et al, 2002;Zubieta et al, 2001Zubieta et al, , 2002Zubieta et al, , 2003a. Therefore, by using positron emission tomography and the radiotracer [ 11 C]carfentanil, labeling mu opioid receptor, Scott et al (2007) in a pilot study examined changes in mu opioid receptor mediated neurotransmission from smoking low (denicotinized) to average nicotine content cigarettes.…”

Section: Direct Involvement Of the Endogenous Opioid System In The Acmentioning

confidence: 99%

“…These are brain areas implicated in the anticipation of reward (Kilts, 2001). In addition, they distinguish between potentially rewarding and nonrewarding outcomes (Knutson et al, 2003), affective modulation, and antinociceptive effects (Rainville et al, 1997;Zubieta et al, 2001). …”

Section: Direct Involvement Of the Endogenous Opioid System In The Acmentioning

confidence: 99%

Tobacco/nicotine and endogenous brain opioids

Xue

Domino

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot! Standard medications to assist in smoking cessation, such as nicotine replacement therapies and bupropion, are ineffective in many remaining smokers. Recent developments in the neurobiology of nicotine dependence have identified several neurotransmitter systems that may contribute to the process of smoking maintenance and relapse. These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking.

show abstract

Regional Mu Opioid Receptor Regulation of Sensory and Affective Dimensions of Pain

Cited by 759 publications

References 48 publications

Negative affect, pain and sex: The role of endogenous opioids

Negative affect, pain and sex: The role of endogenous opioids

Genetic variation in human NPY expression affects stress response and emotion

Tobacco/nicotine and endogenous brain opioids

Contact Info

Product

Resources

About