Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus - Archive ouverte HAL Access content directly
Journal Articles Journal of Headache and Pain Year : 2023

Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus

Jérémy Signoret-Genest
  • Function : Author
Maxime Barnet
  • Function : Author
François Gabrielli
Youssef Aissouni
Alain Artola
  • Function : Author
Radhouane Dallel
  • Function : Author
Myriam Antri
  • Function : Author
Lénaïc Monconduit

Abstract

Abstract Background Migraine is a disabling neurological disorder, characterized by recurrent headaches. During migraine attacks, individuals often experience sensory symptoms such as cutaneous allodynia which indicates the presence of central sensitization. This sensitization is prevented by oral administration of propranolol, a common first-line medication for migraine prophylaxis, that also normalized the activation of the locus coeruleus (LC), considered as the main origin of descending noradrenergic pain controls. We hypothesized that the basal modulation of trigeminal sensory processing by the locus coeruleus is shifted towards more facilitation in migraineurs and that prophylactic action of propranolol may be attributed to a direct action in LC through beta-adrenergic receptors. Methods We used simultaneous in vivo extracellular recordings from the trigeminocervical complex (TCC) and LC of male Sprague–Dawley rats to characterize the relationship between these two areas following repeated meningeal inflammatory soup infusions. Von Frey Hairs and air-puff were used to test periorbital mechanical allodynia. RNAscope and patch-clamp recordings allowed us to examine the action mechanism of propranolol. Results We found a strong synchronization between TCC and LC spontaneous activities, with a precession of the LC, suggesting the LC drives TCC excitability. Following repeated dural-evoked trigeminal activations, we observed a disruption in coupling of activity within LC and TCC. This suggested an involvement of the two regions’ interactions in the development of sensitization. Furthermore, we showed the co-expression of alpha-2A and beta-2 adrenergic receptors within LC neurons. Finally propranolol microinjections into the LC prevented trigeminal sensitization by desynchronizing and decreasing LC neuronal activity. Conclusions Altogether these results suggest that trigemino-coerulean coupling plays a pivotal role in migraine progression, and that propranolol’s prophylactic effects involve, to some extent, the modulation of LC activity through beta-2 adrenergic receptors. This insight reveals new mechanistic aspects of LC control over sensory processing.
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Dates and versions

hal-04331348 , version 1 (23-02-2024)

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Jérémy Signoret-Genest, Maxime Barnet, François Gabrielli, Youssef Aissouni, Alain Artola, et al.. Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus. Journal of Headache and Pain, 2023, 24 (1), pp.165. ⟨10.1186/s10194-023-01691-1⟩. ⟨hal-04331348⟩

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