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Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus.
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- Author(s): Signoret-Genest, Jérémy; Barnet, Maxime; Gabrielli, François; Aissouni, Youssef; Artola, Alain; Dallel, Radhouane; Antri, Myriam; Tovote, Philip; Monconduit, Lénaïc
- Source:
Journal of Headache & Pain; 12/8/2023, Vol. 24 Issue 1, p1-16, 16p- Subject Terms:
MIGRAINE prevention; BIOLOGICAL models; IN vitro studies; PROPRANOLOL; NEUROPHYSIOLOGY; PAIN; NEURONS; MIGRAINE; ANIMAL experimentation; ORAL drug administration; BETA adrenoceptors; RH isoimmunization; ADRENERGIC beta blockers; RATS; RESEARCH funding; HEADACHE; BRAIN stem; HYPERALGESIA; PAIN management; CHEMICAL inhibitors - Source:
- Additional Information
- 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. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Journal of Headache & Pain is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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