Nonpharmacological modulation of cortical spreading depolarization

Nash, Christine; Powell, Keren; Lynch, Daniel G.; Hartings, Jed A.; Li, Chunyan

doi:10.1016/j.lfs.2023.121833

Cited by 3 publications

(4 citation statements)

References 193 publications

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“…Upper cervical DRG nerves, such as the greater occipital nerve, are involved in several craniofacial pain conditions, including occipital and post-traumatic brain injury-associated headaches, and migraine that predominantly affects the back of the head [ 1 , 4 , 51 , 52 ]. These sensory neurons are involved in the pain aspects of these disorders, and other symptoms such as aura and neck stiffness [ 3 , 51 , 52 ]. Blocking CGRP alone may not be sufficient for craniofacial pain conditions where the DRG make a substantial contribution because DRG neurons may also express amylin and AMY receptors [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia

Rees,

Tasma,

Garelja

et al. 2024

J Headache Pain

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Background The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG. Methods CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG. Results Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences. Conclusions Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets.

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Section: Discussionmentioning

confidence: 99%

Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia

Rees,

Tasma,

Garelja

et al. 2024

J Headache Pain

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“…The trigeminovascular network is traditionally tied to the generation and pathogenesis of CSDs in migraine (Fregni et al 2007 ). Clinically, however, chronic TNS in migraine results in the decrease of migraine symptomology, which has been ascribed to a potential effect on CSDs (Nash, Powell and White, et al 2023 ; Magis et al 2017 ; Didier et al 2015 ; Russo et al 2015 ).…”

Section: Effects Of Trigeminal Nerve Stimulationmentioning

confidence: 99%

“…This also results in increased GABAergic interneuron firing, thus modulating GABAergic signaling and lowering the firing rate of glutamate neurons (Buck et al 2022 ). This potentially results in the prevention of a self-reinforcing cycle of glutamatergic kainite and NMDA receptor overactivation and further glutamate release, thus affecting CSD propagation (Nash, Powell, White, et al 2023 ). EA-TNS in healthy conditions, however, increases NMDA receptor expression (Gong et al 2022 ).…”

Section: Underlying Mechanisms Of Trigeminal Nerve Stimulationmentioning

confidence: 99%

“…TNS has been observed to induce cerebral vasodilation, modulate cerebral metabolism and neurotransmission, and decrease neuroinflammation (Xu et al 2023 ; Nash, Powell, White, et al 2023 ; Shah et al 2020 ; Chiluwal et al 2017 ; Magis et al 2017 ; Weber et al 2003 ). Systemically, it modulates the autonomic nervous system (ANS), induces peripheral vasoconstriction, decreases systemic inflammation, and modulates cardiac performance (Degiorgio et al 2011 ; Borges and Casselman 2010 ; Shankland 2000 ; Walker 1990 ).…”

Section: Introductionmentioning

confidence: 99%

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Trigeminal nerve stimulation: a current state-of-the-art review

Powell,

Lin,

Tambo

et al. 2023

Bioelectron Med

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Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS’ success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.

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Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

Alok,

White,

2024

Neural Regeneration Research

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Nonpharmacological modulation of cortical spreading depolarization

Cited by 3 publications

References 193 publications

Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia

Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia

Trigeminal nerve stimulation: a current state-of-the-art review

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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