Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain

Brian L. Schmidt; Victoria Pickering; Stanley Liu; Phuong Quang; John Dolan; S. Thaddeus Connelly; Richard C.K. Jordan

doi:10.1016/j.ejpain.2006.05.007

Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain

Brian L. Schmidt, Victoria Pickering, Stanley Liu, Phuong Quang, John Dolan, S. Thaddeus Connelly, Richard C.K. Jordan

Research output: Contribution to journal › Article › peer-review

Abstract

In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 μM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.

Original language	English (US)
Pages (from-to)	406-414
Number of pages	9
Journal	European Journal of Pain
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.ejpain.2006.05.007
State	Published - May 2007

Keywords

Cancer pain
Endothelin
Endothelin A receptor
Mouse model
Oral cancer

ASJC Scopus subject areas

Anesthesiology and Pain Medicine

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10.1016/j.ejpain.2006.05.007

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title = "Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain",

abstract = "In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 μM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.",

keywords = "Cancer pain, Endothelin, Endothelin A receptor, Mouse model, Oral cancer",

author = "Schmidt, {Brian L.} and Victoria Pickering and Stanley Liu and Phuong Quang and John Dolan and Connelly, {S. Thaddeus} and Jordan, {Richard C.K.}",

note = "Funding Information: Grant support: NIH/NIDCR DE14609, PO1DE13904; NIH/NCI CA095231; Tobacco-related disease research program grants 12KT-0166, 11RT-0141. ",

year = "2007",

month = may,

doi = "10.1016/j.ejpain.2006.05.007",

language = "English (US)",

volume = "11",

pages = "406--414",

journal = "European Journal of Pain",

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AU - Schmidt, Brian L.

AU - Pickering, Victoria

AU - Liu, Stanley

AU - Quang, Phuong

AU - Dolan, John

AU - Connelly, S. Thaddeus

AU - Jordan, Richard C.K.

N1 - Funding Information: Grant support: NIH/NIDCR DE14609, PO1DE13904; NIH/NCI CA095231; Tobacco-related disease research program grants 12KT-0166, 11RT-0141.

PY - 2007/5

Y1 - 2007/5

N2 - In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 μM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.

AB - In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 μM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.

KW - Cancer pain

KW - Endothelin

KW - Endothelin A receptor

KW - Mouse model

KW - Oral cancer

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JO - European Journal of Pain

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ER -

Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain

Abstract

Keywords

ASJC Scopus subject areas

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