Cargando…
Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity
Peripheral hypersensitivity is a significant side effect with the chronic administration of opioids as well as chemotherapeutics. Both opioid-induced hypersensitivity (OIH) and chemotherapy induced hypersensitivity (CIH) are characterized by an increased sensitivity to painful stimuli which can sign...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197749/ https://www.ncbi.nlm.nih.gov/pubmed/37214851 http://dx.doi.org/10.21203/rs.3.rs-2883270/v1 |
_version_ | 1785044606176460800 |
---|---|
author | Jessup, Dawn Woods, Kareem Thakker, Sach Damaj, M. Imad Akbarali, Hamid I. |
author_facet | Jessup, Dawn Woods, Kareem Thakker, Sach Damaj, M. Imad Akbarali, Hamid I. |
author_sort | Jessup, Dawn |
collection | PubMed |
description | Peripheral hypersensitivity is a significant side effect with the chronic administration of opioids as well as chemotherapeutics. Both opioid-induced hypersensitivity (OIH) and chemotherapy induced hypersensitivity (CIH) are characterized by an increased sensitivity to painful stimuli which can significantly reduce the quality of life for individuals on either drug(s). Here we demonstrate the peripheral hypersensitivity associated with chronic morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate. In two separate mouse behavioral models for peripheral hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by co-treatment with oral butyrate. Electrophysiological recordings of small diameter dorsal root ganglia (DRG) neurons from morphine and paclitaxel treated mice showed an increase in neuronal hyperexcitability in both drug models which was likewise prevented by oral butyrate treatment. Using colonic conditioned media obtained from excised colon segments we found that gut mediators of morphine treated mice can induce hyperexcitability in naïve DRG neurons, but such enhanced excitability is not present when animals are co-treated with butyrate suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro butyrate treatment did not prevent morphine induced excitability, suggesting an indirect role of sodium butyrate in modulating neuronal hypersensitivity. These data taken together suggest that gut derived mediators affect opioid and chemotherapeutic induced neuronal hypersensitivity that is prevented by the SCFA butyrate. |
format | Online Article Text |
id | pubmed-10197749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-101977492023-05-20 Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity Jessup, Dawn Woods, Kareem Thakker, Sach Damaj, M. Imad Akbarali, Hamid I. Res Sq Article Peripheral hypersensitivity is a significant side effect with the chronic administration of opioids as well as chemotherapeutics. Both opioid-induced hypersensitivity (OIH) and chemotherapy induced hypersensitivity (CIH) are characterized by an increased sensitivity to painful stimuli which can significantly reduce the quality of life for individuals on either drug(s). Here we demonstrate the peripheral hypersensitivity associated with chronic morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate. In two separate mouse behavioral models for peripheral hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by co-treatment with oral butyrate. Electrophysiological recordings of small diameter dorsal root ganglia (DRG) neurons from morphine and paclitaxel treated mice showed an increase in neuronal hyperexcitability in both drug models which was likewise prevented by oral butyrate treatment. Using colonic conditioned media obtained from excised colon segments we found that gut mediators of morphine treated mice can induce hyperexcitability in naïve DRG neurons, but such enhanced excitability is not present when animals are co-treated with butyrate suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro butyrate treatment did not prevent morphine induced excitability, suggesting an indirect role of sodium butyrate in modulating neuronal hypersensitivity. These data taken together suggest that gut derived mediators affect opioid and chemotherapeutic induced neuronal hypersensitivity that is prevented by the SCFA butyrate. American Journal Experts 2023-05-12 /pmc/articles/PMC10197749/ /pubmed/37214851 http://dx.doi.org/10.21203/rs.3.rs-2883270/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Jessup, Dawn Woods, Kareem Thakker, Sach Damaj, M. Imad Akbarali, Hamid I. Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title | Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title_full | Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title_fullStr | Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title_full_unstemmed | Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title_short | Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity |
title_sort | short-chain fatty acid, butyrate prevents morphine and paclitaxel induced peripheral hypersensitivity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197749/ https://www.ncbi.nlm.nih.gov/pubmed/37214851 http://dx.doi.org/10.21203/rs.3.rs-2883270/v1 |
work_keys_str_mv | AT jessupdawn shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducedperipheralhypersensitivity AT woodskareem shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducedperipheralhypersensitivity AT thakkersach shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducedperipheralhypersensitivity AT damajmimad shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducedperipheralhypersensitivity AT akbaralihamidi shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducedperipheralhypersensitivity |