Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia
| العنوان: | Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia |
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| المؤلفون: | Girolamo Calo, Remo Guerrini, Yu-Chun Chiu, Chia Chun Hor, Lih-Chu Chiou, Ming Tatt Lee, Hsin Jung Lee, Yu-Ting Chiu |
| المصدر: | Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-15 (2020) Journal of Biomedical Science |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cannabinoid receptor, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, lcsh:Medicine, Substance P, Pharmacology, Mice, chemistry.chemical_compound, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Neuropeptide S, Orexin Receptors, Pharmacology (medical), Chemistry, Glutamate receptor, Neuropeptide S, Orexin, Substance P, Metabotropic glutamate receptor, Endocannabinoid, Periaqueductal gray, General Medicine, CB1, Metabotropic Glutamate 5, Endocannabinoid system, Endocannabinoid, Metabotropic glutamate receptor, Orexin, Periaqueductal gray, Animals, Neuropeptides, Receptor, Metabotropic Glutamate 5, Stress, Psychological, Ventral Thalamic Nuclei, Analgesia, Receptor, Stress, NO, 03 medical and health sciences, mental disorders, Cannabinoid, Molecular Biology, Research, Biochemistry (medical), lcsh:R, Cell Biology, Blockade, 030104 developmental biology, nervous system, Psychological, 030217 neurology & neurosurgery |
| الوصف: | Background Stress-induced analgesia (SIA) is an evolutionarily conserved phenomenon during stress. Neuropeptide S (NPS), orexins, substance P, glutamate and endocannabinoids are known to be involved in stress and/or SIA, however their causal links remain unclear. Here, we reveal an unprecedented sequential cascade involving these mediators in the lateral hypothalamus (LH) and ventrolateral periaqueductal gray (vlPAG) using a restraint stress-induced SIA model. Methods Male C57BL/6 mice of 8–12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice. Results NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice. Conclusions These results suggest that, during stress, NPS is released and activates LH orexin neurons via NPSRs, releasing orexins in the vlPAG. Orexins then activate OX1Rs on substance P-containing neurons in the vlPAG to release substance P that subsequently. Activates NK1Rs on glutamatergic neurons to release glutamate. Glutamate then activates perisynaptic mGlu5Rs to initiate the endocannabinoid retrograde inhibition of GABAergic transmission in the vlPAG, leading to analgesia. |
| اللغة: | English |
| تدمد: | 1423-0127 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2431a8326753b1661e3a5d82baba6b65Test https://doaj.org/article/53f537b86a584716bdf814fb935a0b18Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2431a8326753b1661e3a5d82baba6b65 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230127 |
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