Recent Progress in Understanding the Mechanisms of Pain and Itch: the Second Special Issue

Ji, Ru-Rong

doi:10.1007/s12264-018-0204-z

Cited by 20 publications

(18 citation statements)

References 40 publications

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“…Recent progress has advanced our understanding of molecular and cellular mechanisms of itch (Ji, 2018; LaMotte et al, 2014; Meixiong and Dong, 2017), including but not limited to the receptors of itch (Alemi et al, 2013; Liu et al, 2009; Liu et al, 2010; Wilson et al, 2013b), the neurotransmitters and neuromodulators of itch (Kardon et al, 2014; Mishra and Hoon, 2013; Sun and Chen, 2007), and especially the itch-mediating neurons and neurocircuits (Bourane et al, 2015; Han et al, 2013; Huang et al, 2018; Mishra and Hoon, 2013; Roberson et al, 2013; Ross et al, 2010; Sun et al, 2017; Sun et al, 2009). Primary sensory neurons especially nociceptors express TRPA1 for pain sensation and sensitization (Bautista et al, 2006; Patapoutian et al, 2009; Story et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

Han

Liu

Convertino

et al. 2018

Neuron

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SUMMARY Increasing evidence suggests that extracellular miRNAs may serve as biomarkers of diseases, but the physiological relevance of extracellular miRNA is unclear. We find that intradermal cheek injection of miR-711 induces TRPA1-depedent itch (scratching) without pain (wiping) in naïve mice. Extracellular perfusion of miR-711 induces TRPA1 currents in both Trpa1-expressing heterologous cells and native sensory neurons through the core sequence GGGACCC. Computer simulations reveal that the core sequence binds several residues at the extracellular S5-S6 loop of TRPA1, which are critical for TRPA1 activation by miR-711 but not allyl isothiocyanate. Intradermal inoculation of human Myla cells induces lymphoma and chronic itch in immune- deficient mice, associated with increased serum levels of miR-711, secreted from cancer cells. Lymphoma-induced chronic itch is suppressed by miR-711 inhibitor and a blocking peptide that disrupts the miR-711/TRPA1 interaction. Our findings demonstrated an unconventional physiological role of extracellular naked miRNAs as itch mediators and ion channel modulators.

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Section: Introductionmentioning

confidence: 99%

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

Han

Liu

Convertino

et al. 2018

Neuron

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“…Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by disorders of intestinal motility and accompanied by chronic abdominal pain [ 1 – 3 ]. The treatment of chronic abdominal pain is difficult [ 4 ]. Research on this disease is progressing slowly due to the lack of suitable animal models.…”

Section: Introductionmentioning

confidence: 99%

Neonatal Maternal Deprivation Followed by Adult Stress Enhances Adrenergic Signaling to Advance Visceral Hypersensitivity

et al. 2018

Neurosci. Bull.

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The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β2 adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β2 adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β2 adrenergic signaling in DRGs.

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“…Recent progress has advanced our understanding regarding the mechanisms of itch (LaMotte et al, 2014;Ji, 2018;Cevikbas and Lerner, 2019). The itch sensation is initiated by the activation of distinct populations of primary pruriceptors expressing MAS-related GPR receptors (Mrgpr), histamine receptors, 5-HT receptors, and natriuretic peptide B (Nppb) by a variety of pruritogens Han et al, 2013;Mishra and Hoon, 2013;Pan et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Central opioid receptors mediate morphine-induced itch and chronic itch

Wang

Jiang

Yao

et al. 2020

Preprint

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Opioids, such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal (i.t.) administration. Recent progress has advanced our understanding of itch circuits in the spinal cord. However, the mechanisms underlying opioid-induced itch are not fully understood, although an interaction between µ-opioid receptor (MOR) and gastrin-releasing peptide receptor (GRPR) in spinal GRPRexpressing neurons has been implicated. In this study we investigated the cellular mechanisms of intrathecal (i.t.) opioid-induced itch by conditional deletion of MOR-encoding Oprm1 in distinct populations of interneurons and sensory neurons. We found that i.t. injection of the MOR agonists morphine or DAMGO elicited dose-dependent scratching, but this pruritus was totally abolished in mice with a specific Oprm1 deletion in Vgat + neurons (Oprm1-Vgat). Loss of MOR in somatostatin + interneurons and TRPV1 + sensory neurons did not affect morphine-induced itch but impaired morphine-induced antinociception. In situ hybridization revealed Oprm1 expression in 30% of inhibitory and 20% of excitatory interneurons in the spinal dorsal horn. Whole-cell recordings from spinal cord slices showed that DAMGO induced outward currents in 9 out of 19 Vgat + interneurons examined. Morphine also inhibited action potentials in Vgat + interneurons and suppressed evoked IPSCs in postsynaptic Vgatexcitatory neurons, suggesting a mechanism of disinhibition by MOR agonists. Notably, morphine-elicited itch was suppressed by i.t. administration of NPY and abolished by spinal ablation of GRPR + neurons, whereas i.t. GRPinduced itch response remained intact in mice lacking Oprm1-Vgat. Additionally, chronic itch from DNFB-induced allergic contact dermatitis was decreased by Oprm1-Vgat deletion. Finally, naloxone, but not peripherally restricted naloxone methiodide, inhibited chronic itch in the DNFB model and the cutaneous T-cell lymphoma (CTCL) model, indicating a contribution of central MOR signaling to chronic itch. Our findings demonstrate that i.t. morphine elicits itch via acting on MOR on spinal inhibitory interneurons, leading to disinhibition of the spinal itch circuit. Our data also suggest that chronic itch could be effectively treated with CNS-targeted naloxone.

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Recent Progress in Understanding the Mechanisms of Pain and Itch: the Second Special Issue

Cited by 20 publications

References 40 publications

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

Neonatal Maternal Deprivation Followed by Adult Stress Enhances Adrenergic Signaling to Advance Visceral Hypersensitivity

Central opioid receptors mediate morphine-induced itch and chronic itch

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