Evidence map›Paper›PMID 34504741›Full record

ReviewJournal of bone oncology2021

Sensory nerves: A driver of the vicious cycle in bone metastasis?

Toshiyuki Yoneda, Masahiro Hiasa, Tatsuo Okui, Kenji Hata

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of bone oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  5. Neuro-tumor interactions in peripheral tumors.Cancer metastasis reviews · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Toshiyuki YonedaDepartment of Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
Masahiro HiasaDepartment of Biomaterials and Bioengineerings, University of Tokushima Graduate School of Dentistry, Tokushima, Japan.
Tatsuo OkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
Kenji HataDepartment of Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
Osaka University · JPOkayama University · JPTokushima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated by autonomic nerves (ANs) (sympathetic and parasympathetic nerves) and SNs. Recent studies have shown that the nerves innervating the tumor microenvironment establish intimate communications with tumors, producing various stimuli for tumors to progress and disseminate. In this review, our current understanding of the role of SNs innervating bone in the pathophysiology of CABP will be overviewed. Then the hypothesis that SNs facilitate cancer progression in bone will be discussed in conjunction with our recent findings that SNs play an important role not only in the induction of CABP but also the progression of bone metastasis using a preclinical model of CABP. It is suggested that SNs are a critical component of the bone microenvironment that drives the vicious cycle between bone and cancer to progress bone metastasis. Suppression of the activity of bone-innervating SNs may have potential therapeutic effects on the progression of bone metastasis and induction of CABP.

Indexed as

a3V-H+-ATPase, a3 isoform vacuolar proton pumpAN, autonomic nerveBDNF, brain-derived neurotrophic factorBMP, bone morphogenetic proteinBMSC, bone marrow stromal cellsBone microenvironmentCABP, cancer-associated bone painCALCRL, calcitonin receptor-like receptorCancer-associated bone painCAP, cancer-associated painCCL2, C–C motif chemokine 2CGRP, calcitonin gene-related peptideCNS, central nervous systemCOX, cyclooxygenaseCREB, cyclic AMP-responsive element-binding proteinCRPC, castration-resistant prostate cancerCXCL1, C-X-C Motif Chemokine Ligand 1CXCL2, C-X-C Motif Chemokine Ligand 2DRG, dorsal root ganglionERK1/2, extracellular receptor kinase ½G-CSF, granulocyte colony-stimulating factorGDNF, glial-derived neurotrophic factorHGF, hepatocyte growth factorHIF-1α, hypoxia-inducible transcription factor-1αHMGB-1, high mobility group box-1HSCs, hematopoietic stem cellsHUVECs, human umbilical vein endothelial cellsIL-1β, interleukin 1βMM, multiple myelomaMOR, mu-opioid receptorNE, norepinephrineNGF, nerve growth factorNI, nerve invasionNociceptorsNPY, neuropeptide YNSAIDs, nonsteroidal anti-inflammatory drugsOA, osteoarthritisOPG, osteoprotegerinPACAP, pituitary adenylate cyclase-activating peptidePanIN, pancreatic intraepithelial neoplasiaPD-1, programmed cell death-1PDAC, pancreatic ductal adenocarcinomaPD-L1, programmed death-ligand 1Perineural invasionPGE2, prostaglandin E2PNI, perineural invasionRAGE, receptor for advanced glycation end productsRAMP1, receptor activity modifying protein 1RANKL, receptor activator of NF-κB ligandRTX, resiniferatoxinSensory nervesSN, sensory nervesSP, substance PSRE, skeletal-related eventTGFβ, transforming growth factor βTNFα, tumor necrosis factor αTrkA, tyrosine kinase receptor type 1TRPV1VEGF, vascular endothelial growth factorVIP, vasoactive intestinal peptide

Identifiers

PMID34504741
PMCPMC8411232
OpenAlexW3194462699

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.