Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches.
Animals
Brain-Derived Neurotrophic Factor
/ administration & dosage
Male
Administration, Intranasal
Rats, Sprague-Dawley
Recombinant Proteins
/ administration & dosage
Rats
Humans
Disease Models, Animal
Hyperalgesia
/ drug therapy
Migraine Disorders
/ drug therapy
Sumatriptan
/ administration & dosage
Pituitary Adenylate Cyclase-Activating Polypeptide
/ administration & dosage
Cytokines
/ blood
Nitroglycerin
/ administration & dosage
Brain
/ drug effects
BDNF
Cluster headache
Intranasal administration
Migraine
Neuroinflammation
Neurotrophins
Journal
The journal of headache and pain
ISSN: 1129-2377
Titre abrégé: J Headache Pain
Pays: England
ID NLM: 100940562
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
06
09
2024
accepted:
15
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors. In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague-Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration. Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP. The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.
Sections du résumé
BACKGROUND
BACKGROUND
In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors.
METHODS
METHODS
In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague-Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration.
RESULTS
RESULTS
Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP.
CONCLUSIONS
CONCLUSIONS
The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.
Identifiants
pubmed: 39455939
doi: 10.1186/s10194-024-01890-4
pii: 10.1186/s10194-024-01890-4
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Recombinant Proteins
0
BDNF protein, human
7171WSG8A2
Sumatriptan
8R78F6L9VO
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Cytokines
0
Nitroglycerin
G59M7S0WS3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
184Informations de copyright
© 2024. The Author(s).
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