ArticleThe journal of pain2013
Angiotensin II receptor type 2 activation is required for cutaneous sensory hyperinnervation and hypersensitivity in a rat hind paw model of inflammatory pain.
Article in The journal of pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- A Practical Solution for Dyspareunia in Breast Cancer Survivors: A Randomized Controlled Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Angiotensin II type 1 and type 2 receptors modulate TWIK1 channel expression and pain sensitivity in a rat model of neuropathic pain.Frontiers in pharmacology · 2026Article
- Differential Regulation of Intracisternally Injected Angiotensin II-Induced Mechanical Allodynia and Thermal Hyperalgesia in Rats.Biomedicines · 2023Article
- Angiotensin II type 2 receptor signalling as a pain target: Bench, bedside and back-translation.Current opinion in pharmacology · 2023Review
- Review
- Nonopioid analgesics discovery and the Valley of Death: EMA401 from concept to clinical trial.Pain · 2022Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Peripheral mechanisms of chronic pain.Medical review (2021) · 2022Review
- Neuroimmune interactions and immunoengineering strategies in peripheral nerve repair.Progress in neurobiology · 2022Review
- Shedding Light on the Pharmacological Interactions between μ-Opioid Analgesics and Angiotensin Receptor Modulators: A New Option for Treating Chronic Pain.Molecules (Basel, Switzerland) · 2021Review
- The Angiotensin II Type 2 Receptor, a Target for Protection and Regeneration of the Peripheral Nervous System?Pharmaceuticals (Basel, Switzerland) · 2021Review
- Baroreceptor Modulation of the Cardiovascular System, Pain, Consciousness, and Cognition.Comprehensive Physiology · 2021Article
- Angiotensin receptors and neuropathic pain.Pain reports · 2021Review
- Angiotensin Type 2 Receptors: Painful, or Not?Frontiers in pharmacology · 2020Review
- Correlated Sensory and Sympathetic Innervation Between the Acupoint BL23 and Kidney in the Rat.Frontiers in integrative neuroscience · 2020Article
- Emerging Evidence of Macrophage Contribution to Hyperinnervation and Nociceptor Sensitization in Vulvodynia.Frontiers in molecular neuroscience · 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
- Inflammatory Renin-Angiotensin System Disruption Attenuates Sensory Hyperinnervation and Mechanical Hypersensitivity in a Rat Model of Provoked Vestibulodynia.The journal of pain · 2018Article
- Neuronal cytoskeletal gene dysregulation and mechanical hypersensitivity in a rat model of Rett syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledMany pain syndromes are associated with abnormal proliferation of peripheral sensory fibers. We showed previously that angiotensin II, acting through its type 2 receptor (AT2), stimulates axon outgrowth by cultured dorsal root ganglion neurons. In this study, we assessed whether AT2 mediates nociceptor hyperinnervation in the rodent hind paw model of inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA), but not saline, produced marked thermal and mechanical hypersensitivity through 7 days. This was accompanied by proliferation of dermal and epidermal PGP9.5-immunoreactive (ir) and calcitonin gene-related peptide-immunoreactive (CGRP-ir) axons, and dermal axons immunoreactive for GFRα2 but not tyrosine hydroxylase or neurofilament H. Continuous infusion of the AT2 antagonist PD123319 beginning with CFA injection completely prevented hyperinnervation as well as hypersensitivity over a 7-day period. A single PD123319 injection 7 days after CFA also reversed thermal hypersensitivity and partially reversed mechanical hypersensitivity 3 hours later, without affecting cutaneous innervation. Angiotensin II-synthesizing proteins renin and angiotensinogen were largely absent after saline but abundant in T cells and macrophages in CFA-injected paws with or without PD123319. Thus, emigrant cells at the site of inflammation apparently establish a renin-angiotensin system, and AT2 activation elicits nociceptor sprouting and heightened thermal and mechanical sensitivity. PERSPECTIVE: Short-term AT2 activation is a potent contributor to thermal hypersensitivity, whereas long-term effects (such as hyperinnervation) also contribute to mechanical hypersensitivity. Pharmacologic blockade of AT2 signaling represents a potential therapeutic strategy aimed at biologic mechanisms underlying chronic inflammatory pain.
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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.