eprintid: 10106986
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/10/69/86
datestamp: 2020-08-07 10:45:24
lastmod: 2021-09-25 23:22:58
status_changed: 2020-08-07 10:45:24
type: article
metadata_visibility: show
creators_name: Kucharczyk, MW
creators_name: Chisholm, KI
creators_name: Denk, F
creators_name: Dickenson, AH
creators_name: Bannister, K
creators_name: McMahon, SB
title: The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
note: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
abstract: Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer-induced bone pain (CIBP) is mediated by peripheral sensory neurons innervating the cancerous site, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode sensory information in CIBP remains only partly explained. Using a validated rat model, we first confirmed cortical bone destruction in CIBP but not sham-operated rats (day 14 after surgery, designated “late”-stage bone cancer). This occurred with behavioural mechanical hypersensitivity (Kruskal–Wallis H for independent samples; CIBP vs sham-operated, day 14; P < 0.0001). Next, hypothesising that the proportion and phenotype of primary afferents would be altered in the disease state, dorsal root ganglia in vivo imaging of genetically encoded calcium indicators and Markov Cluster Analysis were used to analyse 1748 late-stage CIBP (n = 10) and 757 sham-operated (n = 9), neurons. Distinct clusters of responses to peripheral stimuli were revealed. In CIBP rats, upon knee compression of the leg ipsilateral to the tumour, (1) 3 times as many sensory afferents responded (repeated-measures analysis of variance: P < 0.0001 [vs sham]); (2) there were significantly more small neurons responding (Kruskal–Wallis for independent samples (vs sham): P < 0.0001); and (3) approximately 13% of traced tibial cavity afferents responded (no difference observed between CIBP and sham-operated animals). We conclude that an increased sensory afferent response is present in CIBP rats, and this is likely to reflect afferent recruitment from outside of the bone rather than increased intraosseous afferent activity.
date: 2020-08
date_type: published
official_url: https://doi.org/10.1097/j.pain.0000000000001880
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1777829
doi: 10.1097/j.pain.0000000000001880
pii: 00006396-202008000-00022
lyricists_name: Bannister, Kirsty
lyricists_name: Dickenson, Anthony
lyricists_id: KBANN82
lyricists_id: AHDIC08
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Pain
volume: 161
number: 8
pagerange: 1894-1905
event_location: United States
citation:        Kucharczyk, MW;    Chisholm, KI;    Denk, F;    Dickenson, AH;    Bannister, K;    McMahon, SB;      (2020)    The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli.                   Pain , 161  (8)   pp. 1894-1905.    10.1097/j.pain.0000000000001880 <https://doi.org/10.1097/j.pain.0000000000001880>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10106986/1/The_impact_of_bone_cancer_on_the_peripheral.22.pdf