The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females

Chen, Yanxia; Moutal, Aubin; Navratilova, Edita; Kopruszinski, Caroline Machado; Yue, Xu; Ikegami, Megumi; Chow, M. S.; Kanazawa, Iori; Bellampalli, Shreya S.; Xie, Jennifer Y.; Patwardhan, Amol; Rice, Kenner C.; Fields, Howard L.; Akopian, Armen N.; Neugebauer, Volker; Dodick, David W.; Khanna, Rajesh; Porreca, Frank

doi:10.1126/scitranslmed.aay7550

Cited by 56 publications

(66 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, we plated sensory neurons on multiwell MEAs, an approach enabling multiplexed measurement of spontaneous, as well as stimulus-evoked extracellular action potentials from large populations of cells. 9 Vascular endothelial growth factor-A increased spontaneous firing of DRG neurons, which was blocked by the S1 domain of the spike protein and by the NRP-1 inhibitor EG00229 (Fig. 1 A).…”

Section: Resultsmentioning

confidence: 96%

SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia

Moutal¹,

Martin

Boinon³

et al. 2020

Pain

Self Cite

134

152

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 96%

SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia

Moutal¹,

Martin

Boinon³

et al. 2020

Pain

Self Cite

134

152

View full text Add to dashboard Cite

show abstract

“…1A). Next, we plated sensory neurons on multiwell microelectrode arrays (MEAs), an approach enabling multiplexed measurements of spontaneous, as well as stimulus-evoked extracellular action potentials from large populations of cells [9]. VEGF-A increased spontaneous firing of dorsal root ganglion (DRG) neurons, which was blocked by the S1 domain of the Spike protein and by the NRP-1 inhibitor EG00229 (Fig.…”

Section: Ligand Specific Engagement Of Nrp-1 Signaling Induces Nocicementioning

confidence: 99%

SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

Moutal

Martin

Boinon

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2's Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A 'silencing' of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.

show abstract

“…Malplasticity of multiple components in the pain transmission pathway is implicated in OIH. Sensitization of peripheral nociceptors and second-order neurons in the spinal cord, long-term potentiation (LTP), and descending facilitation are among the best characterized forms of neuronal malplasticity proposed for OIH expression 3,5,7,8,47,48 . These and other lines of evidence suggest the importance of malplasticity of excitatory systems in OIH expression 7 .…”

Section: Neuronal Circuitry Mechanism In the Development Of Oihmentioning

confidence: 99%

Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling

Liu

et al. 2021

Preprint

View full text Add to dashboard Cite

Opioid analgesics are the frontline pain medicine for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH). OIH significantly contributes to dose escalation and consequently opioid overdose. In addition to neuronal malplasticity, emerging evidence suggests a critical role of reactive glia in OIH development. A potential astrocytic underpinning of OIH pathogenesis is indicated by their prominently activation in OIH animal models. However, this hypothesis has not been conclusively tested and the mechanism underlying the astrocyte activation remains unclear. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in mice. Genetic ablation of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We also found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1β. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.

show abstract

The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females

Cited by 56 publications

References 73 publications

SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia

SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia

SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling

Contact Info

Product

Resources

About