Kappa-opioid receptor-mediated thermal analgesia evoked by the intrathecal administration of the chemokine CCL1 in mice.
| Autor: | García-Domínguez M; Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., González-Rodríguez S; Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Hidalgo A; Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Baamonde A; Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Menéndez L; Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. |
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| Jazyk: | angličtina |
| Zdroj: | Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2021 Dec; Vol. 35 (6), pp. 1109-1118. Date of Electronic Publication: 2021 May 19. |
| DOI: | 10.1111/fcp.12685 |
| Abstrakt: | Background: The chemokine CC motif ligand 1 (CCL1) participates in immune cell recruitment and, as other chemokines, is also involved in nociceptive processing. In contrast with previous reports indicating its participation in allodynia and cold hypernociception when spinally administered, its ability to evoke heat thermal analgesia, mediated by circulating leukocytes and endocannabinoids, after systemic administration has recently been reported. Objectives: Aiming to explore the role played by CCL1 on spinal nociception, we study here the effect of its intrathecal administration on thermal nociception in mice. Methods: Behavioral nociceptive assays, immunohistochemical experiments, white cell blood depletion procedures and qRT-PCR experiments were performed. Results: The intrathecal administration of CCL1 (0.3-30 ng) produced analgesia as measured by the unilateral hot plate test. This effect peaked 1 h after injection, was prevented by the CCR8 antagonist R243 and was accompanied by a reduction of c-Fos expression in spinal neurons. Whereas blood leukocyte depletion did not modify it, analgesia was abolished by the microglial inhibitor minocycline, but not the astroglial inhibitor aminoadipate. Furthermore, antinociception remained unmodified by the coadministration of cannabinoid type 1 or 2 receptors antagonists. However, it was reversed by naloxone but not by selective blockade of mu- or delta-opioid receptors. The inhibitory effect induced by the selective kappa-opioid receptor antagonist, nor-binaltorphimine, and by an anti-dynorphin A 1-17 antibody indicates that analgesia evoked by spinal CCL1 is mediated by endogenous dynorphins acting on kappa-opioid receptors. Conclusions: Endogenous dynorphin and microglia behave as key players in heat thermal analgesia evoked by spinal CCL1 in mice. (© 2021 Société Française de Pharmacologie et de Thérapeutique.) |
| Databáze: | MEDLINE |
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