Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia

Autor: Girolamo Calo, Remo Guerrini, Yu-Chun Chiu, Chia Chun Hor, Lih-Chu Chiou, Ming Tatt Lee, Hsin Jung Lee, Yu-Ting Chiu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
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
Zdroj: Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-15 (2020)
Journal of Biomedical Science
ISSN: 1423-0127
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje