IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1744-9081-10-5 http://hdl.handle.net/11449/113488 |
Resumo: | Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics. |
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IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinomaIsolectin B4TRPV1Squamous cell carcinomaCancer painProliferationBackground: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.NIH/NIDCRNYU, Bluestone Ctr Clin Res, New York, NY 10003 USAUniv Michigan, Dept Oral & Maxillofacial Surg, Ann Arbor, MI 48109 USANYU, Dept Oral & Maxillofacial Surg, New York, NY USANYU, Dept Otolaryngol Head & Neck Surg, New York, NY USAUniv Estadual Paulista, Aracatuba Dent Sch, Oral Oncol Ctr, Aracatuba, San Paulo, BrazilUniv Estadual Paulista, Aracatuba Dent Sch, Oral Oncol Ctr, Aracatuba, San Paulo, BrazilNIH/NIDCRR21 DE018561NIH/NIDCRR01 DE19796Biomed Central Ltd.NYUUniversity of MichiganUniversidade Estadual Paulista (Unesp)Ye, YiBae, Sam S.Viet, Chi T.Troob, ScottBernabe, Daniel [UNESP]Schmidt, Brian L.2014-12-03T13:11:44Z2014-12-03T13:11:44Z2014-02-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://dx.doi.org/10.1186/1744-9081-10-5Behavioral And Brain Functions. London: Biomed Central Ltd, v. 10, 10 p., 2014.1744-9081http://hdl.handle.net/11449/11348810.1186/1744-9081-10-5WOS:000332984300002WOS000332984300002.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBehavioral and Brain Functions2.4490,986info:eu-repo/semantics/openAccess2024-04-11T20:16:34Zoai:repositorio.unesp.br:11449/113488Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:13:46.469969Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
title |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
spellingShingle |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma Ye, Yi Isolectin B4 TRPV1 Squamous cell carcinoma Cancer pain Proliferation |
title_short |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
title_full |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
title_fullStr |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
title_full_unstemmed |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
title_sort |
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma |
author |
Ye, Yi |
author_facet |
Ye, Yi Bae, Sam S. Viet, Chi T. Troob, Scott Bernabe, Daniel [UNESP] Schmidt, Brian L. |
author_role |
author |
author2 |
Bae, Sam S. Viet, Chi T. Troob, Scott Bernabe, Daniel [UNESP] Schmidt, Brian L. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
NYU University of Michigan Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Ye, Yi Bae, Sam S. Viet, Chi T. Troob, Scott Bernabe, Daniel [UNESP] Schmidt, Brian L. |
dc.subject.por.fl_str_mv |
Isolectin B4 TRPV1 Squamous cell carcinoma Cancer pain Proliferation |
topic |
Isolectin B4 TRPV1 Squamous cell carcinoma Cancer pain Proliferation |
description |
Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-12-03T13:11:44Z 2014-12-03T13:11:44Z 2014-02-13 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1744-9081-10-5 Behavioral And Brain Functions. London: Biomed Central Ltd, v. 10, 10 p., 2014. 1744-9081 http://hdl.handle.net/11449/113488 10.1186/1744-9081-10-5 WOS:000332984300002 WOS000332984300002.pdf |
url |
http://dx.doi.org/10.1186/1744-9081-10-5 http://hdl.handle.net/11449/113488 |
identifier_str_mv |
Behavioral And Brain Functions. London: Biomed Central Ltd, v. 10, 10 p., 2014. 1744-9081 10.1186/1744-9081-10-5 WOS:000332984300002 WOS000332984300002.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Behavioral and Brain Functions 2.449 0,986 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd. |
publisher.none.fl_str_mv |
Biomed Central Ltd. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129597878829056 |