Cancer chemotherapy in early life significantly alters the maturation of pain processing

Advances in paediatric cancer treatment have led to a ten year survival rate greater than 75%. Platinum-based chemotherapies (e.g.cisplatin) induce peripheral sensory neuropathy in adult and paedriatric cancer patients. The period from birth through to adulthood represents a period of maturation wit...

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Main Authors: Hathway, Gareth J., Murphy, Emily, Lloyd, Joseph, Greenspon, Charles M., Hulse, Richard P.
Format: Article
Published: Elsevier 2017
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Online Access:https://eprints.nottingham.ac.uk/48459/
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author Hathway, Gareth J.
Murphy, Emily
Lloyd, Joseph
Greenspon, Charles M.
Hulse, Richard P.
author_facet Hathway, Gareth J.
Murphy, Emily
Lloyd, Joseph
Greenspon, Charles M.
Hulse, Richard P.
author_sort Hathway, Gareth J.
building Nottingham Research Data Repository
collection Online Access
description Advances in paediatric cancer treatment have led to a ten year survival rate greater than 75%. Platinum-based chemotherapies (e.g.cisplatin) induce peripheral sensory neuropathy in adult and paedriatric cancer patients. The period from birth through to adulthood represents a period of maturation within nociceptive systems. Here we investigated how cisplatin impacts upon postnatal maturation of nociceptive systems. Neonatal Wistar rats (Postnatal day (P) 7) were injected (i.p.) daily with either vehicle (PBS) or cisplatin (1mg/kg) for five consecutive days. Neither group developed mechanical or thermal hypersensitivity immediately during or after treatment. At P22 the cisplatin group developed mechanical (P<0.05) and thermal (P<0.0001) hypersensitivity versus vehicle group. Total DRG or dorsal horn neuronal number did not differ at P45, however there was an increase in intraepidermal nerve fibre density in cisplatin treated animals at this age. The percentage of IB4+ve, CGRP+ve and NF200+ve DRG neurons was not different between groups at P45. There was an increase in TrkA+ve DRG neurons in the cisplatin group at P45, in addition to increased TrkA, NF200 and vGLUT2 immunoreactivity in the lumbar dorsal horn versus controls. These data highlight the impact paediatric cancer chemotherapy has upon the maturation of pain pathways and later life pain experience.
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spelling nottingham-484592024-08-15T15:25:29Z https://eprints.nottingham.ac.uk/48459/ Cancer chemotherapy in early life significantly alters the maturation of pain processing Hathway, Gareth J. Murphy, Emily Lloyd, Joseph Greenspon, Charles M. Hulse, Richard P. Advances in paediatric cancer treatment have led to a ten year survival rate greater than 75%. Platinum-based chemotherapies (e.g.cisplatin) induce peripheral sensory neuropathy in adult and paedriatric cancer patients. The period from birth through to adulthood represents a period of maturation within nociceptive systems. Here we investigated how cisplatin impacts upon postnatal maturation of nociceptive systems. Neonatal Wistar rats (Postnatal day (P) 7) were injected (i.p.) daily with either vehicle (PBS) or cisplatin (1mg/kg) for five consecutive days. Neither group developed mechanical or thermal hypersensitivity immediately during or after treatment. At P22 the cisplatin group developed mechanical (P<0.05) and thermal (P<0.0001) hypersensitivity versus vehicle group. Total DRG or dorsal horn neuronal number did not differ at P45, however there was an increase in intraepidermal nerve fibre density in cisplatin treated animals at this age. The percentage of IB4+ve, CGRP+ve and NF200+ve DRG neurons was not different between groups at P45. There was an increase in TrkA+ve DRG neurons in the cisplatin group at P45, in addition to increased TrkA, NF200 and vGLUT2 immunoreactivity in the lumbar dorsal horn versus controls. These data highlight the impact paediatric cancer chemotherapy has upon the maturation of pain pathways and later life pain experience. Elsevier 2017-12-02 Article PeerReviewed Hathway, Gareth J., Murphy, Emily, Lloyd, Joseph, Greenspon, Charles M. and Hulse, Richard P. (2017) Cancer chemotherapy in early life significantly alters the maturation of pain processing. Neuroscience . ISSN 1873-7544 (In Press) cisplatin; neuropathy; pain; hyperalgesia; development; postnatal https://www.sciencedirect.com/science/article/pii/S0306452217308266 doi:10.1016/j.neuroscience.2017.11.032 doi:10.1016/j.neuroscience.2017.11.032
spellingShingle cisplatin; neuropathy; pain; hyperalgesia; development; postnatal
Hathway, Gareth J.
Murphy, Emily
Lloyd, Joseph
Greenspon, Charles M.
Hulse, Richard P.
Cancer chemotherapy in early life significantly alters the maturation of pain processing
title Cancer chemotherapy in early life significantly alters the maturation of pain processing
title_full Cancer chemotherapy in early life significantly alters the maturation of pain processing
title_fullStr Cancer chemotherapy in early life significantly alters the maturation of pain processing
title_full_unstemmed Cancer chemotherapy in early life significantly alters the maturation of pain processing
title_short Cancer chemotherapy in early life significantly alters the maturation of pain processing
title_sort cancer chemotherapy in early life significantly alters the maturation of pain processing
topic cisplatin; neuropathy; pain; hyperalgesia; development; postnatal
url https://eprints.nottingham.ac.uk/48459/
https://eprints.nottingham.ac.uk/48459/
https://eprints.nottingham.ac.uk/48459/