Decreased pain responses of C–C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli

Lee, Yong Kyoung; Choi, Dong‐Young; Jung, Yoon Young; Yun, Young Won; Lee, Beom Jun; Han, Sang Bae; Hong, Jin Tae

doi:10.1016/j.neuropharm.2012.10.030

Cited by 36 publications

(33 citation statements)

References 57 publications

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“…A study that examined effects of CCR5 deficiency on pain responses by employing CCR5 KO mice found that pain responses of CCR5 KO mice to chemical or inflammatory stimuli were milder than those of CCR5 wild-type mice [251]. Though the roles of proinflammatory cytokines and chemokines in neuropathic pain have been identified [252], the precise relationship between the chemokine-cytokine network and neuropathic pain is not yet well understood.…”

Section: Cytokines and Chemokines In Neuropathic Painmentioning

confidence: 99%

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Ramesh

MacLean

Philipp

2013

Mediators of Inflammation

512

412

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Cytokines and chemokines are proteins that coordinate the immune response throughout the body. The dysregulation of cytokines and chemokines is a central feature in the development of neuroinflammation, neurodegeneration, and demyelination both in the central and peripheral nervous systems and in conditions of neuropathic pain. Pathological states within the nervous system can lead to activation of microglia. The latter may mediate neuronal and glial cell injury and death through production of proinflammatory factors such as cytokines and chemokines. These then help to mobilize the adaptive immune response. Although inflammation may induce beneficial effects such as pathogen clearance and phagocytosis of apoptotic cells, uncontrolled inflammation can result in detrimental outcomes via the production of neurotoxic factors that exacerbate neurodegenerative pathology. In states of prolonged inflammation, continual activation and recruitment of effector cells can establish a feedback loop that perpetuates inflammation and ultimately results in neuronal injury. A critical balance between repair and proinflammatory factors determines the outcome of a neurodegenerative process. This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.

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Section: Cytokines and Chemokines In Neuropathic Painmentioning

confidence: 99%

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Ramesh

MacLean

Philipp

2013

Mediators of Inflammation

512

412

View full text Add to dashboard Cite

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“…administration of these two chemokines induces pain behaviors, and this effect might be evoked by CCR5 activation in the dorsal root ganglia (DRG) (Liou et al, 2013). Lee et al (2013) described that CCR5-knockout mice respond less to nociceptive stimuli than wild type mice. Together, these studies strongly suggest that CCR5 plays a crucial role in the development of neuropathic pain symptoms.…”

Section: Introductionmentioning

confidence: 99%

Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats

Kwiatkowski

Piotrowska

Rojewska

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…10–13 Moreover, given the presence of MOR-CCR 5 in cultured cells, it appears likely that such heteromers may also exist in vivo. 14, 15 Here we report on a series of ligands that contains both mu opioid agonist and chemokine CCR 5 antagonist pharmacophores tethered through homologous spacers.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR₅)

et al. 2015

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Chemokine release promotes crosstalk between opioid and chemokine receptors that in part leads to reduced efficacy of morphine in the treatment of chronic pain. Based on the possibility that a MOR-CCR5 heteromer is involved in such crosstalk, we have synthesized bivalent ligands (MCC series) that contain mu opioid agonist and CCR5 antagonist pharmacophores linked through homologous spacers (14–24 atoms). When tested on lipopolysaccharide-inflamed mice, a member of the series (MCC22; 3e) with a 22-atom spacer exhibited profound antinociception (i.t. ED50 = 0.0146 pmol/mouse) that was >2000× greater than morphine. Moreover, MCC22 was ~3500× more potent than a mixture of mu agonist and CCR5 antagonist monovalent ligands. These data strongly suggest that MCC22 acts by bridging the protomers of a MOR-CCR5 heteromer having a TM5,6 interface. Molecular simulation studies are consistent with such bridging. This study supports the MOR-CCR5 heteromer as a novel target for treatment of chronic pain.

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Decreased pain responses of C–C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli

Cited by 36 publications

References 57 publications

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats

Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR₅)

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Decreased pain responses of C–C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli

Cited by 36 publications

References 57 publications

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats

Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5)

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Product

Resources

About

Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR₅)