Chemotherapy-induced neuropathic pain (CINP) is a common adverse health related comorbidity that manifests later in life in paediatric cancer patients. Current analgesia is ineffective, aligning closely with our lack of understanding of CINP. The aim of this study was to investigate how cisplatin induces nerve growth factor mediated neuroinflammation and nociceptor sensitisation. In a rodent model of cisplatin induced survivorship pain, cisplatin induced a neuroinflammatory environment in the dorsal root ganglia (DRG) demonstrated by nerve growth factor (NGF) positive macrophages infiltrating into the DRG. Cisplatin treated CD11b/F480 positive macrophages expressed more NGF compared to vehicle treated. Primary DRG sensory neuronal cultures demonstrated enhanced NGF-dependent TRPV1 mediated nociceptor activity after cisplatin treatment. Increased nociceptor activity was also observed when cultured DRG neurons were treated with conditioned media from cisplatin activated macrophages. Elevated nociceptor activity was dose-dependently inhibited by a neutralising NGF antibody. Intraperitoneal administration of a NGF neutralising antibody reduced cisplatin-induced mechanical hypersensitivity and aberrant nociceptor intraepidermal nerve fibre density. These findings identify that a monocyte/macrophage driven NGF/TrkA pathway is a novel analgesic target for adult survivors of childhood cancer.
Early life cisplatin exposure induces nerve growth factor mediated neuroinflammation and chemotherapy induced neuropathic pain
- Award Group:
- Funder(s): European Foundation for the Study of Diabetes
- Award Id(s): Nov 2015_2
- Funder(s):
- Award Group:
- Funder(s): European Foundation for the Study of Diabetes
- Award Id(s): BI18_5
- Funder(s):
- Award Group:
- Funder(s): Rosetrees Trust
- Award Id(s): A1360
- Funder(s):
- Award Group:
- Funder(s): Nottingham Trent University
- Funder(s):
Marlene Da Vitoria Lobo, Lydia Hardowar, Tameille Valentine, Lucy Tomblin, Charlotte Guest, Dhyana Sharma, Benjamin Dickins, Mark Paul-Clark, Richard Philip Hulse; Early life cisplatin exposure induces nerve growth factor mediated neuroinflammation and chemotherapy induced neuropathic pain. Dis Model Mech 2024; dmm.052062. doi: https://doi.org/10.1242/dmm.052062
Download citation file:
Advertisement
Cited by
Call for Papers – Infectious Disease: Evolution, Mechanisms and Global Health
Showcase your latest research on our upcoming Special Issue: Infectious Disease: Evolution, Mechanisms and Global Health. This issue will be coordinated by DMM Editors Sumana Sanyal and David Tobin alongside Guest Editors Judi Allen and Russell Vance. The deadline for submitting articles to this Special Issue is Monday 20 January 2025.
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate a DMM programme on antimicrobial resistance on 26 March 2025. Find out more and register to join us in March 2025 in Liverpool, UK.
New Special Issue: Translating Multiscale Research in Rare Disease. Edited by Monica Justice, Monkol Lek, Karen Liu and Kate Rauen.
This special issue features original Research, Resources & Methods and Review-type articles that aim to interrogate the mechanisms of rare diseases to foster meaningful clinical progress in their diagnosis and treatment.
The role of the International Society for Stem Cell Research guidelines in disease modelling
The International Society for Stem Cell Research (ISSCR) provides comprehensive guidelines and standards for using human stem cells in biomedical research. In this Editorial, Cody Juguilon and Joseph Wu discuss how and why these should be incorporated in disease modelling research.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
Other journals from
The Company of Biologists