Cargando…

Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity

Nociceptive 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 sig...

Descripción completa

Detalles Bibliográficos
Autores principales: Jessup, Dawn, Woods, Kareem, Thakker, Sach, Damaj, M. Imad, Akbarali, Hamid I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584825/
https://www.ncbi.nlm.nih.gov/pubmed/37853033
http://dx.doi.org/10.1038/s41598-023-44857-2
_version_ 1785122820304404480
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 Nociceptive 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 nociceptive hypersensitivity associated with repeated administration of morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate (NaBut). In two separate mouse behavioral models for nociceptive hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by treatment with oral butyrate (p.o, b.i.d). 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 NaBut suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro NaBut treatment did not prevent morphine-induced excitability, suggesting an indirect role of 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-10584825
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-105848252023-10-20 Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity Jessup, Dawn Woods, Kareem Thakker, Sach Damaj, M. Imad Akbarali, Hamid I. Sci Rep Article Nociceptive 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 nociceptive hypersensitivity associated with repeated administration of morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate (NaBut). In two separate mouse behavioral models for nociceptive hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by treatment with oral butyrate (p.o, b.i.d). 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 NaBut suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro NaBut treatment did not prevent morphine-induced excitability, suggesting an indirect role of 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. Nature Publishing Group UK 2023-10-18 /pmc/articles/PMC10584825/ /pubmed/37853033 http://dx.doi.org/10.1038/s41598-023-44857-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jessup, Dawn
Woods, Kareem
Thakker, Sach
Damaj, M. Imad
Akbarali, Hamid I.
Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title_full Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title_fullStr Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title_full_unstemmed Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title_short Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
title_sort short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584825/
https://www.ncbi.nlm.nih.gov/pubmed/37853033
http://dx.doi.org/10.1038/s41598-023-44857-2
work_keys_str_mv AT jessupdawn shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducednociceptivehypersensitivity
AT woodskareem shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducednociceptivehypersensitivity
AT thakkersach shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducednociceptivehypersensitivity
AT damajmimad shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducednociceptivehypersensitivity
AT akbaralihamidi shortchainfattyacidbutyratepreventsmorphineandpaclitaxelinducednociceptivehypersensitivity