Ca<sup>2+</sup>/Calmodulin-Dependent Protein Kinase IIα Is Required for the Initiation and Maintenance of Opioid-Induced Hyperalgesia

Chen, Yan; Yang, Cheng; Wang, Zaijie Jim

doi:10.1523/jneurosci.4346-09.2010

Cited by 75 publications

(98 citation statements)

References 69 publications

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“…Prefrontal cortex sections were quickly dissected on ice and frozen on dry ice for western blotting analysis as described previously (Luo et al, 2008;Chen et al, 2010). Tissues were homogenized in ice-cold radioimmunoprecipitation assay buffer in the presence of protease inhibitors and phosphatase inhibitors and centrifuged.…”

Section: Methodsmentioning

confidence: 99%

“…Previous work by our laboratory and others demonstrated that Ca 21 /calmodulin-dependent protein kinase II a (CaMKIIa) is critically important for the development and maintenance of opioid tolerance, opioid dependence, and opioid-induced hyperalgesia (Chen et al, 2010). CaMKIIa is a multifunctional serine/ threonine protein kinase that is abundantly expressed in the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity

Huang

Szymusiak

et al. 2014

J Pharmacol Exp Ther

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Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca 21 /calmodulin-dependent protein kinase II a (CaMKIIa), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug's poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGAcurcumin nanoparticles reduced the dose requirement by 11-to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dosedependent manner, with ED 50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED 50 5 12.6 mg/kg p.o.) and dependence (ED 50 5 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1-10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIa activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIa activity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity

Huang

Szymusiak

et al. 2014

J Pharmacol Exp Ther

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“…We complemented this data by analyzing the expression of two kinase isoforms, PKA-RIIβ and CaMKIIα, involved in pain sensitization of nociceptors (Brüggemann et al, 2000;Chen et al, 2010;Isensee et al, 2014a). With the exception of CaMKIIα, all marker proteins were already detectable at birth, but changed their cellular expression pattern during aging ( Figs 2B and 3).…”

Section: Basal Characterization Of Sensory Neurons Rats From P0 To 24mentioning

confidence: 96%

“…phosphorylates, and thereby modulates, ion channels including TRPV1, and has been implicated in pain regulation (Chen et al, 2010;Ferrari et al, 2013Ferrari et al, , 2014Hucho et al, 2012;Jung et al, 2004). Microarray data suggest that CaMKIIα mRNA is upregulated fivefold between neonatal and adult DRG neurons (Zhu and Oxford, 2011), but measurements at the protein level are missing.…”

Section: Camkiiα Expression Develops Postnatally and Is Maintained Thmentioning

confidence: 99%

Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging

Isensee

Schild

Schwede

et al. 2017

Journal of Cell Science

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Maturation of nociceptive neurons depends on changes in transcription factors, ion channels and neuropeptides. Mature nociceptors initiate pain in part by drastically reducing the activation threshold via intracellular sensitization signaling. Whether sensitization signaling also changes during development and aging remains so far unknown. Using a novel automated microscopy approach, we quantified changes in intracellular signaling protein expression and in their signaling dynamics, as well as changes in intracellular signaling cascade wiring, in sensory neurons from newborn to senescent (24 months of age) rats. We found that nociceptive subgroups defined by the signaling components protein kinase A (PKA)-RIIβ (also known as PRKAR2B) and CaMKIIα (also known as CAMK2A) developed at around postnatal day 10, the time of nociceptor maturation. The integrative nociceptor marker, PKA-RIIβ, allowed subgroup segregation earlier than could be achieved by assessing the classical markers TRPV1 and Na v 1.8 (also known as SCN10A). Signaling kinetics remained constant over lifetime despite in part strong changes in the expression levels. Strikingly, we found a mechanism important for neuronal memory -i.e. the crosstalk from cAMP and PKA to ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) -to emerge postnatally. Thus, maturation of nociceptors is closely accompanied by altered expression, activation and connectivity of signaling pathways known to be central for pain sensitization and neuronal memory formation.

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“…. Other targets" calcium-modulating serine/threonine protein kinase present in the CNS, Ca 2+ /calmodulin protein kinase II CaMKII , has been of recent interest as a modulator of neuropathic pain and is an important contributor to initiation and maintenance of opioid-induced hyperalgesia [94]. Recently, in a limited clinical trial, 18 SCD patients were treated with single dosage of triluoperazine a CaMKII inhibitor going up to 10 mg, and eight subjects reported almost 0% reduction in their chronic pain.…”

mentioning

confidence: 99%

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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Pain is one of the most common features of sickle cell disease SCD lacking efective therapy. Pain in SCD is relatively more complicated than other conditions associated with pain requiring understanding of the pathobiology of pain speciic to SCD. The characterization of pain to deine the diverse modalities of nociception in SCD is currently under progress via human studies accompanied by transgenic mouse models of SCD. Sickle pathobiology characterized by oxidative stress, inlammation and vascular dysfunction contributes to both peripheral and central nociceptive sensitization via mast cell activation in the periphery, and reactive oxygen species and glial activation and endoplasmic reticulum stress in the spinal cord among other efectors. These efects are mediated via several cellular receptors, which can be targeted to produce positive therapeutic outcomes. In this chapter, we will discuss the present understanding of molecular mechanisms of SCD pain and outline the mechanism-based translational potential of novel actionable targets to treat SCD pain.Keywords: pain, sickle cell disease, neurogenic inlammation, substance P, mast cell . IntroductionPain is a hallmark feature of sickle cell disease SCD , which can start in infancy, leading to hospitalization, reduced survival and poor quality of life. Pain in SCD is unique because of unpredictable and recurrent episodes of acute pain due to vaso-occlusive crises VOC , in addition to chronic pain experienced by a majority of adult patients on a daily basis [1]. Treatment choices remain limited to opioids, which impose liabilities of their own including constipation, mast cell activation, fear of addiction and respiratory depression [2]. Moreover, signiicantly larger doses of opioids are required to treat pain in SCD as compared to other acute and chronic pain conditions [1]. Pain can be lifelong in SCD and may therefore inluence © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.cognitive function and lead to depression and anxiety, which can in turn promote the perception of pain [1].Treatment of chronic pain remains unsatisfactory overall, perhaps due to the diverse pathobiology in diferent diseases. Therefore, it is critical to understand the mechanisms speciic to the genesis of sickle pain to develop targeted therapies. Vascular dysfunction, inlammation, ischemia/reperfusion injury and oxidative stress in the wake of VOC can each evoke activation of the nociceptive nerve ibers leading to acute pain. On the other hand, con...

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Ca²⁺/Calmodulin-Dependent Protein Kinase IIα Is Required for the Initiation and Maintenance of Opioid-Induced Hyperalgesia

Cited by 75 publications

References 69 publications

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity

Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging

Mechanisms of Pain in Sickle Cell Disease

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Ca2+/Calmodulin-Dependent Protein Kinase IIα Is Required for the Initiation and Maintenance of Opioid-Induced Hyperalgesia

Cited by 75 publications

References 69 publications

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging

Mechanisms of Pain in Sickle Cell Disease

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Product

Resources

About

Ca²⁺/Calmodulin-Dependent Protein Kinase IIα Is Required for the Initiation and Maintenance of Opioid-Induced Hyperalgesia

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca²⁺/Calmodulin-Dependent Protein Kinase II α Activity