Novel animal models of acute and chronic cancer pain

A pivotal role for PAR2

David K. Lam, Dongmin Dang, Jianan Zhang, John C. Dolan, Brian Schmidt

Research output: Contribution to journalArticle

Abstract

Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2- serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.

Original languageEnglish (US)
Pages (from-to)14178-14183
Number of pages6
JournalJournal of Neuroscience
Volume32
Issue number41
DOIs
StatePublished - Oct 10 2012

Fingerprint

PAR-2 Receptor
Chronic Pain
Animal Models
Serine Proteases
Acute Pain
Up-Regulation
Cancer Pain
Neoplasms
Tumor Microenvironment
Neck Pain
Head and Neck Neoplasms
Peripheral Nerves
Trypsin
Maintenance

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Novel animal models of acute and chronic cancer pain : A pivotal role for PAR2. / Lam, David K.; Dang, Dongmin; Zhang, Jianan; Dolan, John C.; Schmidt, Brian.

In: Journal of Neuroscience, Vol. 32, No. 41, 10.10.2012, p. 14178-14183.

Research output: Contribution to journalArticle

Lam, David K. ; Dang, Dongmin ; Zhang, Jianan ; Dolan, John C. ; Schmidt, Brian. / Novel animal models of acute and chronic cancer pain : A pivotal role for PAR2. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 41. pp. 14178-14183.
@article{9e8ccfbf4c4a4d3c9cec7f950f5ea4b4,
title = "Novel animal models of acute and chronic cancer pain: A pivotal role for PAR2",
abstract = "Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2- serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.",
author = "Lam, {David K.} and Dongmin Dang and Jianan Zhang and Dolan, {John C.} and Brian Schmidt",
year = "2012",
month = "10",
day = "10",
doi = "10.1523/JNEUROSCI.2399-12.2012",
language = "English (US)",
volume = "32",
pages = "14178--14183",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "41",

}

TY - JOUR

T1 - Novel animal models of acute and chronic cancer pain

T2 - A pivotal role for PAR2

AU - Lam, David K.

AU - Dang, Dongmin

AU - Zhang, Jianan

AU - Dolan, John C.

AU - Schmidt, Brian

PY - 2012/10/10

Y1 - 2012/10/10

N2 - Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2- serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.

AB - Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2- serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.

UR - http://www.scopus.com/inward/record.url?scp=84867245616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867245616&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2399-12.2012

DO - 10.1523/JNEUROSCI.2399-12.2012

M3 - Article

VL - 32

SP - 14178

EP - 14183

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 41

ER -