Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain
The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the...
Gespeichert in:
| Veröffentlicht in: | The journal of pain 2024-03, Vol.25 (3), p.715-729 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 729 |
|---|---|
| container_issue | 3 |
| container_start_page | 715 |
| container_title | The journal of pain |
| container_volume | 25 |
| creator | Rêgo, Débora S.B. Calió, Michele Longoni Filev, Renato Mello, Luiz E. Leslie, Ana T.F.S. |
| description | The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund’s adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life.
The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.
•Lower doses of cannabidiol with fentanyl were associated with anxiety behavior in adult life.•Animals showed dimorphic behavior in supraspinal pain sensitivity.•Females demonstrated greater pain sensitivity when re-exposed to a thermal nociceptive stimulus. |
| doi_str_mv | 10.1016/j.jpain.2023.10.001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2876636402</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1526590023005746</els_id><sourcerecordid>2876636402</sourcerecordid><originalsourceid>FETCH-LOGICAL-c309t-17b85f20299c9c8840371f5ae2666502d7404abd5a1e4b4959eeccd0e38ce41e3</originalsourceid><addsrcrecordid>eNp9kE1PAyEQhonR-FH9BSaGo5etsMuy7MGDaepH0qjx42ZCWJg1NFuoQI3-e6lVj56GTJ6Z4X0QOqZkTAnlZ_PxfKmsG5ekrHJnTAjdQvu0LkUhGGu2v9-8qFtC9tBBjPMM0LppdtFe1YiSCMb30cvMu9ciQVjgad-DThH7Hk-Uc6qzxvoBK2fOfMCX4JJynwOefix9XAXA1uEHlfnHVbewKYHByeNb8E4lNeD7_LVDtNOrIcLRTx2h58vp0-S6mN1d3UwuZoWuSJsK2nSi7nOMttWtFoKRqqF9raDknNekNA0jTHWmVhRYx9q6BdDaEKiEBkahGqHTzd5l8G8riEkubNQwDMqBX0VZiobzirMsaoSqDaqDjzFAL5fBLlT4lJTItVY5l99a5Vrrupmt5amTnwM5K5i_mV-PGTjfAJBjvlsIMmoLToOxIUuVxtt_D3wBRCyJPA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2876636402</pqid></control><display><type>article</type><title>Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Rêgo, Débora S.B. ; Calió, Michele Longoni ; Filev, Renato ; Mello, Luiz E. ; Leslie, Ana T.F.S.</creator><creatorcontrib>Rêgo, Débora S.B. ; Calió, Michele Longoni ; Filev, Renato ; Mello, Luiz E. ; Leslie, Ana T.F.S.</creatorcontrib><description>The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund’s adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life.
The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.
•Lower doses of cannabidiol with fentanyl were associated with anxiety behavior in adult life.•Animals showed dimorphic behavior in supraspinal pain sensitivity.•Females demonstrated greater pain sensitivity when re-exposed to a thermal nociceptive stimulus.</description><identifier>ISSN: 1526-5900</identifier><identifier>EISSN: 1528-8447</identifier><identifier>DOI: 10.1016/j.jpain.2023.10.001</identifier><identifier>PMID: 37820846</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Analgesics, Opioid ; Animals ; anxiety ; Anxiety - chemically induced ; Anxiety - drug therapy ; Cannabidiol - pharmacology ; cannabinoid ; Cannabinoids ; Female ; Fentanyl - pharmacology ; Male ; Neonatal pain ; opioid ; Pain - drug therapy ; Rats ; sex differences</subject><ispartof>The journal of pain, 2024-03, Vol.25 (3), p.715-729</ispartof><rights>2024 United States Association for the Study of Pain, Inc.</rights><rights>Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c309t-17b85f20299c9c8840371f5ae2666502d7404abd5a1e4b4959eeccd0e38ce41e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1526590023005746$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37820846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rêgo, Débora S.B.</creatorcontrib><creatorcontrib>Calió, Michele Longoni</creatorcontrib><creatorcontrib>Filev, Renato</creatorcontrib><creatorcontrib>Mello, Luiz E.</creatorcontrib><creatorcontrib>Leslie, Ana T.F.S.</creatorcontrib><title>Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain</title><title>The journal of pain</title><addtitle>J Pain</addtitle><description>The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund’s adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life.
The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.
•Lower doses of cannabidiol with fentanyl were associated with anxiety behavior in adult life.•Animals showed dimorphic behavior in supraspinal pain sensitivity.•Females demonstrated greater pain sensitivity when re-exposed to a thermal nociceptive stimulus.</description><subject>Analgesics, Opioid</subject><subject>Animals</subject><subject>anxiety</subject><subject>Anxiety - chemically induced</subject><subject>Anxiety - drug therapy</subject><subject>Cannabidiol - pharmacology</subject><subject>cannabinoid</subject><subject>Cannabinoids</subject><subject>Female</subject><subject>Fentanyl - pharmacology</subject><subject>Male</subject><subject>Neonatal pain</subject><subject>opioid</subject><subject>Pain - drug therapy</subject><subject>Rats</subject><subject>sex differences</subject><issn>1526-5900</issn><issn>1528-8447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PAyEQhonR-FH9BSaGo5etsMuy7MGDaepH0qjx42ZCWJg1NFuoQI3-e6lVj56GTJ6Z4X0QOqZkTAnlZ_PxfKmsG5ekrHJnTAjdQvu0LkUhGGu2v9-8qFtC9tBBjPMM0LppdtFe1YiSCMb30cvMu9ciQVjgad-DThH7Hk-Uc6qzxvoBK2fOfMCX4JJynwOefix9XAXA1uEHlfnHVbewKYHByeNb8E4lNeD7_LVDtNOrIcLRTx2h58vp0-S6mN1d3UwuZoWuSJsK2nSi7nOMttWtFoKRqqF9raDknNekNA0jTHWmVhRYx9q6BdDaEKiEBkahGqHTzd5l8G8riEkubNQwDMqBX0VZiobzirMsaoSqDaqDjzFAL5fBLlT4lJTItVY5l99a5Vrrupmt5amTnwM5K5i_mV-PGTjfAJBjvlsIMmoLToOxIUuVxtt_D3wBRCyJPA</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Rêgo, Débora S.B.</creator><creator>Calió, Michele Longoni</creator><creator>Filev, Renato</creator><creator>Mello, Luiz E.</creator><creator>Leslie, Ana T.F.S.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202403</creationdate><title>Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain</title><author>Rêgo, Débora S.B. ; Calió, Michele Longoni ; Filev, Renato ; Mello, Luiz E. ; Leslie, Ana T.F.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-17b85f20299c9c8840371f5ae2666502d7404abd5a1e4b4959eeccd0e38ce41e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analgesics, Opioid</topic><topic>Animals</topic><topic>anxiety</topic><topic>Anxiety - chemically induced</topic><topic>Anxiety - drug therapy</topic><topic>Cannabidiol - pharmacology</topic><topic>cannabinoid</topic><topic>Cannabinoids</topic><topic>Female</topic><topic>Fentanyl - pharmacology</topic><topic>Male</topic><topic>Neonatal pain</topic><topic>opioid</topic><topic>Pain - drug therapy</topic><topic>Rats</topic><topic>sex differences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rêgo, Débora S.B.</creatorcontrib><creatorcontrib>Calió, Michele Longoni</creatorcontrib><creatorcontrib>Filev, Renato</creatorcontrib><creatorcontrib>Mello, Luiz E.</creatorcontrib><creatorcontrib>Leslie, Ana T.F.S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rêgo, Débora S.B.</au><au>Calió, Michele Longoni</au><au>Filev, Renato</au><au>Mello, Luiz E.</au><au>Leslie, Ana T.F.S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain</atitle><jtitle>The journal of pain</jtitle><addtitle>J Pain</addtitle><date>2024-03</date><risdate>2024</risdate><volume>25</volume><issue>3</issue><spage>715</spage><epage>729</epage><pages>715-729</pages><issn>1526-5900</issn><eissn>1528-8447</eissn><abstract>The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund’s adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life.
The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.
•Lower doses of cannabidiol with fentanyl were associated with anxiety behavior in adult life.•Animals showed dimorphic behavior in supraspinal pain sensitivity.•Females demonstrated greater pain sensitivity when re-exposed to a thermal nociceptive stimulus.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37820846</pmid><doi>10.1016/j.jpain.2023.10.001</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1526-5900 |
| ispartof | The journal of pain, 2024-03, Vol.25 (3), p.715-729 |
| issn | 1526-5900 1528-8447 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2876636402 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Analgesics, Opioid Animals anxiety Anxiety - chemically induced Anxiety - drug therapy Cannabidiol - pharmacology cannabinoid Cannabinoids Female Fentanyl - pharmacology Male Neonatal pain opioid Pain - drug therapy Rats sex differences |
| title | Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T20%3A00%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long-term%20Effects%20of%20Cannabidiol%20and/or%20Fentanyl%20Exposure%20in%20Rats%20Submitted%20to%20Neonatal%20Pain&rft.jtitle=The%20journal%20of%20pain&rft.au=R%C3%AAgo,%20D%C3%A9bora%20S.B.&rft.date=2024-03&rft.volume=25&rft.issue=3&rft.spage=715&rft.epage=729&rft.pages=715-729&rft.issn=1526-5900&rft.eissn=1528-8447&rft_id=info:doi/10.1016/j.jpain.2023.10.001&rft_dat=%3Cproquest_cross%3E2876636402%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2876636402&rft_id=info:pmid/37820846&rft_els_id=S1526590023005746&rfr_iscdi=true |