Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion
Autor: | Sze Chi Tsai, Jin-Chung Chen, Po Hung Hsu, Zachary Yu, Ya Tin Lin |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
medicine.medical_specialty
Short Report Neuropeptide FF receptor lcsh:Medicine Stimulation Calcitonin gene-related peptide Neuropeptide FF (NPFF) 03 medical and health sciences chemistry.chemical_compound Trigeminal ganglion 0302 clinical medicine NPFFR2 Downregulation and upregulation Neuromodulation Internal medicine Medicine Neuropeptide FF CGRP Migraine 030304 developmental biology 0303 health sciences Trigeminovascular pathway integumentary system business.industry lcsh:R Headache General Medicine Anesthesiology and Pain Medicine Endocrinology medicine.anatomical_structure chemistry Capsaicin Neurology (clinical) business 030217 neurology & neurosurgery |
Zdroj: | The Journal of Headache and Pain, Vol 21, Iss 1, Pp 1-8 (2020) The Journal of Headache and Pain |
ISSN: | 1129-2377 1129-2369 |
Popis: | Background Stimulation of trigeminovascular pathway is widely used to establish the headache animal model. Headache is a common neurological disorder, in which symptomatic attacks are mediated by calcitonin-gene-related peptide (CGRP). CGRP is synthesized and released from the trigeminal ganglion to transmit pain signals under stimulation. On the other hand, Neuropeptide FF (NPFF) is a candidate transmitter/modulator for migraine, and stimulation of its receptor, NPFFR2, increases the expression and release of CGRP in mice sensory neurons. Here, we investigate the impact of NPFFR2 on trigeminal CGRP level in a capsaicin-induced headache mouse model. Methods Mice were intracisternally injected with capsaicin into the cisterna magna to activate the trigeminovascular pathway and induce headache symptoms. Mice pretreated with Npffr2-shRNA or NPFFR2 knockouts were adopted to test the impact of NPFFR2 on capsaicin-induced CGRP upregulation in trigeminal ganglion. The gene silencing effect of Npffr2-shRNA in trigeminal ganglion was confirmed by real-time PCR. Trigeminal CGRP level was determined by immunofluorescence staining, and the percentage of CGRP-positive cell was calculated after setting the signal intensity threshold by Image J software. Amount of trigeminal CGRP in NPFFR2 overexpressed mice was also measured by CGRP ELISA. Findings Infusion of capsaicin into the cisterna magna upregulated the CGRP in trigeminal ganglion and induced spontaneous pain behaviors including the reduction of locomotor activity and the increase of freezing behavior. Intracisternal injection of Npffr2-shRNA reduced the mRNA of Npffr2 in trigeminal ganglion. Mice pretreatment with Npffr2-shRNA prevented capsaicin-induced CGRP upregulation in trigeminal ganglion. Similarly, CGRP upregulation was also reduced in NPFFR2 knockout mice. On the contrary, trigeminal CGRP was increased in NPFFR2 overexpressed mice. Conclusions Reducing the level of NPFFR2 leads to the downregulation of capsaicin-induced CGRP in trigeminal ganglion, which would consequently attenuate the activation of trigeminovascular pathway. Thus, NPFFR2 could serve as a potential target for neuromodulation of cephalic pain. |
Databáze: | OpenAIRE |
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