Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain

Pain is one of the most severe concerns in tongue cancer patients. However, the underlying mechanisms of tongue cancer pain are not fully understood. We investigated the molecular mechanisms of tongue cancer-induced mechanical allodynia in the tongue by squamous cell carcinoma (SCC) inoculation in r...

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Autores principales:	Ryo Koyama, Koichi Iwata, Yoshinori Hayashi, Suzuro Hitomi, Ikuko Shibuta, Akihiko Furukawa, Sayaka Asano, Tadayoshi Kaneko, Yoshiyuki Yonehara, Masamichi Shinoda
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microglia pannexin 1 adenosine triphosphate squamous cell carcinoma tongue cancer pain Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ab446784baab47c28861f98478806761
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spelling	oai:doaj.org-article:ab446784baab47c28861f984788067612021-11-11T16:52:45ZPannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain10.3390/ijms2221114041422-00671661-6596https://doaj.org/article/ab446784baab47c28861f984788067612021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11404https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Pain is one of the most severe concerns in tongue cancer patients. However, the underlying mechanisms of tongue cancer pain are not fully understood. We investigated the molecular mechanisms of tongue cancer-induced mechanical allodynia in the tongue by squamous cell carcinoma (SCC) inoculation in rats. The head-withdrawal threshold of mechanical stimulation (MHWT) to the tongue was reduced following SCC inoculation, which was inhibited by intracisternal administration of 10Panx, an inhibitory peptide for pannexin 1 (PANX1) channels. Immunohistochemical analyses revealed that the expression of PANX1 was upregulated in the trigeminal spinal subnucleus caudalis (Vc) following SCC inoculation. The majority of PANX1 immunofluorescence was merged with ionized calcium-binding adapter molecule 1 (Iba1) fluorescence and a part of it was merged with glial fibrillary acidic protein (GFAP) fluorescence. Spike frequencies of Vc nociceptive neurons to noxious mechanical stimulation were significantly enhanced in SCC-inoculated rats, which was suppressed by intracisternal 10Panx administration. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons increased significantly in the Vc after SCC inoculation, which was inhibited by intracisternal 10Panx administration. SCC inoculation-induced MHWT reduction and increased pERK-IR Vc neuron numbers were inhibited by P2X7 purinoceptor (P2X7R) antagonism. Conversely, these effects were observed in the presence of P2X7R agonist in SCC-inoculated rats with PANX1 inhibition. SCC inoculation-induced MHWT reduction was significantly recovered by intracisternal interleukin-1 receptor antagonist administration. These observations suggest that SCC inoculation causes PANX1 upregulation in Vc microglia and adenosine triphosphate released through PANX1 sensitizes nociceptive neurons in the Vc, resulting in tongue cancer pain.Ryo KoyamaKoichi IwataYoshinori HayashiSuzuro HitomiIkuko ShibutaAkihiko FurukawaSayaka AsanoTadayoshi KanekoYoshiyuki YoneharaMasamichi ShinodaMDPI AGarticlemicrogliapannexin 1adenosine triphosphatesquamous cell carcinomatongue cancer painBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11404, p 11404 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microglia pannexin 1 adenosine triphosphate squamous cell carcinoma tongue cancer pain Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	microglia pannexin 1 adenosine triphosphate squamous cell carcinoma tongue cancer pain Biology (General) QH301-705.5 Chemistry QD1-999 Ryo Koyama Koichi Iwata Yoshinori Hayashi Suzuro Hitomi Ikuko Shibuta Akihiko Furukawa Sayaka Asano Tadayoshi Kaneko Yoshiyuki Yonehara Masamichi Shinoda Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
description	Pain is one of the most severe concerns in tongue cancer patients. However, the underlying mechanisms of tongue cancer pain are not fully understood. We investigated the molecular mechanisms of tongue cancer-induced mechanical allodynia in the tongue by squamous cell carcinoma (SCC) inoculation in rats. The head-withdrawal threshold of mechanical stimulation (MHWT) to the tongue was reduced following SCC inoculation, which was inhibited by intracisternal administration of 10Panx, an inhibitory peptide for pannexin 1 (PANX1) channels. Immunohistochemical analyses revealed that the expression of PANX1 was upregulated in the trigeminal spinal subnucleus caudalis (Vc) following SCC inoculation. The majority of PANX1 immunofluorescence was merged with ionized calcium-binding adapter molecule 1 (Iba1) fluorescence and a part of it was merged with glial fibrillary acidic protein (GFAP) fluorescence. Spike frequencies of Vc nociceptive neurons to noxious mechanical stimulation were significantly enhanced in SCC-inoculated rats, which was suppressed by intracisternal 10Panx administration. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons increased significantly in the Vc after SCC inoculation, which was inhibited by intracisternal 10Panx administration. SCC inoculation-induced MHWT reduction and increased pERK-IR Vc neuron numbers were inhibited by P2X7 purinoceptor (P2X7R) antagonism. Conversely, these effects were observed in the presence of P2X7R agonist in SCC-inoculated rats with PANX1 inhibition. SCC inoculation-induced MHWT reduction was significantly recovered by intracisternal interleukin-1 receptor antagonist administration. These observations suggest that SCC inoculation causes PANX1 upregulation in Vc microglia and adenosine triphosphate released through PANX1 sensitizes nociceptive neurons in the Vc, resulting in tongue cancer pain.
format	article
author	Ryo Koyama Koichi Iwata Yoshinori Hayashi Suzuro Hitomi Ikuko Shibuta Akihiko Furukawa Sayaka Asano Tadayoshi Kaneko Yoshiyuki Yonehara Masamichi Shinoda
author_facet	Ryo Koyama Koichi Iwata Yoshinori Hayashi Suzuro Hitomi Ikuko Shibuta Akihiko Furukawa Sayaka Asano Tadayoshi Kaneko Yoshiyuki Yonehara Masamichi Shinoda
author_sort	Ryo Koyama
title	Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
title_short	Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
title_full	Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
title_fullStr	Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
title_full_unstemmed	Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain
title_sort	pannexin 1-mediated atp signaling in the trigeminal spinal subnucleus caudalis is involved in tongue cancer pain
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ab446784baab47c28861f98478806761
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Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain

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