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• W2022641134 abstract "Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment." @default.
• W2022641134 created "2016-06-24" @default.
• W2022641134 creator A5015929707 @default.
• W2022641134 creator A5044937806 @default.
• W2022641134 date "2010-05-01" @default.
• W2022641134 modified "2023-10-14" @default.
• W2022641134 title "Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice" @default.
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• W2022641134 doi "https://doi.org/10.1016/j.pain.2010.02.009" @default.
• W2022641134 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2860690" @default.
• W2022641134 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20206445" @default.
• W2022641134 hasPublicationYear "2010" @default.
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