Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats
The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) ca...
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2022-05-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/5/164 |
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| author | Marek Zubrzycki Maria Zubrzycka Grzegorz Wysiadecki Janusz Szemraj Hanna Jerczynska Mariusz Stasiolek |
| author_facet | Marek Zubrzycki Maria Zubrzycka Grzegorz Wysiadecki Janusz Szemraj Hanna Jerczynska Mariusz Stasiolek |
| author_sort | Marek Zubrzycki |
| collection | DOAJ |
| description | The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain. |
| first_indexed | 2024-03-10T03:05:27Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T03:05:27Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-1d15e549ec70402e9ead491df94e53732023-11-23T10:32:38ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-05-014452401241610.3390/cimb44050164Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in RatsMarek Zubrzycki0Maria Zubrzycka1Grzegorz Wysiadecki2Janusz Szemraj3Hanna Jerczynska4Mariusz Stasiolek5Department of Cardiac Surgery and Transplantology, The Cardinal Stefan Wyszynski Institute of Cardiology, Alpejska 42, 04-628 Warsaw, PolandDepartment of Clinical Physiology, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Normal and Clinical Anatomy, Chair of Anatomy and Histology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandCentral Scientific Laboratory (CoreLab), Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, PolandThe endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.https://www.mdpi.com/1467-3045/44/5/164cerebrospinal fluidorofacial painendocannabinoidscannabinoid receptorsURB597 |
| spellingShingle | Marek Zubrzycki Maria Zubrzycka Grzegorz Wysiadecki Janusz Szemraj Hanna Jerczynska Mariusz Stasiolek Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats Current Issues in Molecular Biology cerebrospinal fluid orofacial pain endocannabinoids cannabinoid receptors URB597 |
| title | Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats |
| title_full | Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats |
| title_fullStr | Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats |
| title_full_unstemmed | Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats |
| title_short | Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats |
| title_sort | release of endocannabinoids into the cerebrospinal fluid during the induction of the trigemino hypoglossal reflex in rats |
| topic | cerebrospinal fluid orofacial pain endocannabinoids cannabinoid receptors URB597 |
| url | https://www.mdpi.com/1467-3045/44/5/164 |
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