ArticlePain2015
Induction of thermal and mechanical hypersensitivity by parathyroid hormone-related peptide through upregulation of TRPV1 function and trafficking.
Article in Pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Decoding migraine disorders: parathyroid hormone-related peptide receptors as key genetic drivers.Brain communications · 2025Article
- Caldendrin Is a Repressor of PIEZO2 Channels and Touch Sensation in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1.European journal of pain (London, England) · 2022Article
- Regulation of the firing activity by PKA-PKC-Src family kinases in cultured neurons of hypothalamic arcuate nucleus.Journal of neuroscience research · 2020Article
- Female-Specific Effects of CGRP Suggest Limited Efficacy of New Migraine Treatments in Males.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats.Molecular brain · 2019Article
- Article
- Neuronal transient receptor potential (TRP) channels and noxious sensory detection in sickle cell disease.Neuroscience letters · 2019Review
- TRPV1 channel contributes to remifentanil-induced postoperative hyperalgesia via regulation of NMDA receptor trafficking in dorsal root ganglion.Journal of pain research · 2019Article
- Macrophage angiotensin II type 2 receptor triggers neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Angiotensin II Triggers Peripheral Macrophage-to-Sensory Neuron Redox Crosstalk to Elicit Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice.Neuropharmacology · 2018Article
- Deficits in Burrowing Behaviors Are Associated With Mouse Models of Neuropathic but Not Inflammatory Pain or Migraine.Frontiers in behavioral neuroscience · 2018Article
- Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity.Frontiers in cellular neuroscience · 2018Article
- Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study.BJU international · 2017Article
- Recent advances in acute pain management: understanding the mechanisms of acute pain, the prescription of opioids, and the role of multimodal pain therapy.F1000Research · 2017Review
- Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies.Pharmaceuticals (Basel, Switzerland) · 2016Review
- The Complement System Component C5a Produces Thermal Hyperalgesia via Macrophage-to-Nociceptor Signaling That Requires NGF and TRPV1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel.Molecular pain · 2016Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. Intraplantar injection of PTHrP led to the development of thermal and mechanical hypersensitivity in both male and female mice, which were absent in mice lacking functional transient receptor potential vanilloid-1 (TRPV1). The PTHrP treatment of cultured mouse sensory neurons enhanced action potential firing, and increased TRPV1 activation, which was dependent on protein kinase C (PKC) activity. Parathyroid hormone-related peptide induced robust potentiation of TRPV1 activation and enhancement of neuronal firing at mild acidic pH that is relevant to acidic tumor microenvironment. We also observed an increase in plasma membrane TRPV1 protein levels after exposure to PTHrP, leading to upregulation in the proportion of TRPV1-responsive neurons, which was dependent on the activity of PKC and Src kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP-induced thermal but not mechanical hypersensitivity. Altogether, our results suggest that PTHrP and mild acidic conditions could induce constitutive pathological activation of sensory neurons through upregulation of TRPV1 function and trafficking, which could serve as a mechanism for peripheral sensitization of nociceptive afferents in the tumor microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.