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Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation.
Int J Mol Sci. 2020 Nov 25; 21(23)IJ

Abstract

The opioid-induced analgesia is associated with a number of side effects such as addiction, tolerance and respiratory depression. The involvement of neuropeptide FF (NPFF) in modulation of pain perception, opioid-induced tolerance and dependence was well documented in contrast to respiratory depression. Therefore, the aim of the present study was to examine the potency of NPFF to block post-opioid respiratory depression, one of the main adverse effects of opioid therapy. Urethane-chloralose anaesthetized Wistar rats were injected either intravenously (iv) or intracerebroventricularly (icv) with various doses of NPFF prior to iv endomorphin-1 (EM-1) administration. Iv NPFF diminished the number of EM-1-induced apneas without affecting their length and without influence on the EM-1 induced blood pressure decline. Icv pretreatment with NPFF abolished the occurrence of post-EM-1 apneas and reduced also the maximal drop in blood pressure and heart rate. These effects were completely blocked by the NPFF receptor antagonist RF9, which was given as a mixture with NPFF before systemic EM-1 administration. In conclusion, our results showed that centrally administered neuropeptide FF is effective in preventing apnea evoked by stimulation of μ-opioid receptors and the effect was due to activation of central NPFF receptors. Our finding indicates a potential target for reversal of opioid-induced respiratory depression.

Authors+Show Affiliations

Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-105 Warsaw, Poland.Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-105 Warsaw, Poland.Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-105 Warsaw, Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33255594

Citation

Wojciechowski, Piotr, et al. "Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced By Opioid Receptors' Activation." International Journal of Molecular Sciences, vol. 21, no. 23, 2020.
Wojciechowski P, Andrzejewski K, Kaczyńska K. Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation. Int J Mol Sci. 2020;21(23).
Wojciechowski, P., Andrzejewski, K., & Kaczyńska, K. (2020). Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation. International Journal of Molecular Sciences, 21(23). https://doi.org/10.3390/ijms21238931
Wojciechowski P, Andrzejewski K, Kaczyńska K. Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced By Opioid Receptors' Activation. Int J Mol Sci. 2020 Nov 25;21(23) PubMed PMID: 33255594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation. AU - Wojciechowski,Piotr, AU - Andrzejewski,Kryspin, AU - Kaczyńska,Katarzyna, Y1 - 2020/11/25/ PY - 2020/10/26/received PY - 2020/11/23/revised PY - 2020/11/24/accepted PY - 2020/12/1/entrez PY - 2020/12/2/pubmed PY - 2021/3/6/medline KW - NPFF receptors KW - apnea KW - endomorphin-1 KW - neuropeptide FF KW - μ-opioid receptors JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 23 N2 - The opioid-induced analgesia is associated with a number of side effects such as addiction, tolerance and respiratory depression. The involvement of neuropeptide FF (NPFF) in modulation of pain perception, opioid-induced tolerance and dependence was well documented in contrast to respiratory depression. Therefore, the aim of the present study was to examine the potency of NPFF to block post-opioid respiratory depression, one of the main adverse effects of opioid therapy. Urethane-chloralose anaesthetized Wistar rats were injected either intravenously (iv) or intracerebroventricularly (icv) with various doses of NPFF prior to iv endomorphin-1 (EM-1) administration. Iv NPFF diminished the number of EM-1-induced apneas without affecting their length and without influence on the EM-1 induced blood pressure decline. Icv pretreatment with NPFF abolished the occurrence of post-EM-1 apneas and reduced also the maximal drop in blood pressure and heart rate. These effects were completely blocked by the NPFF receptor antagonist RF9, which was given as a mixture with NPFF before systemic EM-1 administration. In conclusion, our results showed that centrally administered neuropeptide FF is effective in preventing apnea evoked by stimulation of μ-opioid receptors and the effect was due to activation of central NPFF receptors. Our finding indicates a potential target for reversal of opioid-induced respiratory depression. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/33255594/Intracerebroventricular_Neuropeptide_FF_Diminishes_the_Number_of_Apneas_and_Cardiovascular_Effects_Produced_by_Opioid_Receptors'_Activation_ L2 - https://www.mdpi.com/resolver?pii=ijms21238931 DB - PRIME DP - Unbound Medicine ER -