Toward a Multimodal Framework of Brainstem Pain-Modulation Circuits in Migraine

Yanes, Julio A.

doi:10.1523/jneurosci.0301-19.2019

Cited by 5 publications

(8 citation statements)

References 20 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, these nuclei may have a role to play in any potentiation of the responses of trigeminovascular second-order neurons caused by the cortical changes that result from migraine triggers. Such a mechanism is consistent with an increasing number of reports that provide significant evidence throwing doubt on notions that the production of migraine pain is purely due to peripheral dural trigeminovascular mechanisms (8,21–24).…”

Section: Discussionsupporting

confidence: 87%

“…Recent reviews and research reports have highlighted the important role played by various brainstem structures, including the locus coeruleus (8,10,21,24,31) and diencephalic or subcortical structures such as the hypothalamus (21) in migraine, in general, and in migraine headache in particular. Of the nuclei mentioned in our own investigations and reviews (12,32), we chose to investigate the NRM and PAG.…”

Section: Discussionmentioning

confidence: 99%

“…If headache provokers, or triggers, cause changes in cortical excitability, which then produce changes in brainstem control of trigeminovascular sensation by opening the “pain gate”, this could transform often subliminal perceptions caused by innocuous trigeminovascular sensory traffic into the perception of headache. There are several brainstem nuclei that could be involved in such a process (6–11). Based on research by others (listed in our previous review (4)), we suggested that two likely structures that could transform cortical excitability changes into trigeminovascular perception changes are the nucleus raphe magnus (NRM) and the periaqueductal grey matter (PAG) (12).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

et al. 2020

View full text Add to dashboard Cite

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The activation of 5-HT 3 and 5-HT 7 receptors on inhibitory neurons by nVNS would enhance the descending inhibitory pain pathway via activation of spinal interneurons and release of the inhibitory neurotransmitters, GABA and glycine, to suppress ascending pain transmission. This mechanism is supported by other orofacial pain studies involving trigeminal nerve activation in which direct stimulation of the vagus nerve was shown to exhibit anti-nociceptive effects, to facilitate the serotonergic descending inhibition pathway, and to modulate inhibition of GABAergic neurons (14,40,41). Other mechanisms may also be involved in nVNS inhibition of trigeminal pain signaling.…”

Section: Discussionmentioning

confidence: 61%

Inhibition of Trigeminal Nociception by Non-invasive Vagus Nerve Stimulation: Investigating the Role of GABAergic and Serotonergic Pathways in a Model of Episodic Migraine

2020

View full text Add to dashboard Cite

Migraine is a prevalent neurological disease that is characterized by unpredictable episodic attacks of intense head pain. The underlying pathology involves sensitization and activation of the trigeminal system. Although non-invasive vagus nerve stimulation (nVNS) is recommended for the treatment of migraine, the abortive mechanism of action is not well-understood. The goal of this study was to compare the ability of nVNS and sumatriptan to inhibit trigeminal activation in two animal models of episodic migraine and to investigate the receptor mechanism of action of nVNS. Nocifensive head withdrawal response was investigated in adult male Sprague Dawley rats using von Frey filaments. To induce trigeminal nociceptor sensitization, complete Freund's adjuvant was injected in the trapezius muscle and trigeminal neurons were activated by exposure to a pungent odor or injection of the nitric oxide donor sodium nitroprusside. Some animals received nVNS or sumatriptan as treatment. Some animals were injected intracisternally with antagonists of GABA A , 5-HT3 or 5-HT7 receptors prior to nVNS since these receptors are implicated in descending modulation. While unsensitized animals exposed to the pungent odor or nitric oxide alone did not exhibit enhanced mechanical nociception, sensitized animals with neck muscle inflammation displayed increased trigeminal nocifensive responses. The enhanced nociceptive response to both stimuli was attenuated by nVNS and sumatriptan. Administration of antagonists of GABA A , 5-HT3, and 5-HT7 receptors in the upper spinal cord suppressed the anti-nocifensive effect of nVNS. Our findings suggest that nVNS inhibits trigeminal activation to a similar degree as sumatriptan in episodic migraine models via involvement of GABAergic and serotonergic signaling to enhance central descending pain modulation.

show abstract

“…Activation of the serotonergic/GABAergic pathway is involved in the antinociceptive effects in other orofacial pain models. 56 , 57 , 62 Noninvasive vagus nerve stimulation also inhibits elevated cerebrospinal fluid levels of the excitatory neurotransmitter glutamate in a nitroglycerin-induced model of trigeminal allodynia and thus may function to restore neurotransmitter homeostasis. 45 Furthermore, our results provide evidence that nVNS and morphine only transiently suppressed trigeminal nociception because decreased nocifensive levels were no longer observed one day after stopping daily treatment with nVNS or morphine.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive vagus nerve stimulation and morphine transiently inhibit trigeminal pain signaling in a chronic headache model

Cornelison

Hawkins

Woodman

et al. 2020

PR9

View full text Add to dashboard Cite

show abstract

Toward a Multimodal Framework of Brainstem Pain-Modulation Circuits in Migraine

Cited by 5 publications

References 20 publications

A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

Inhibition of Trigeminal Nociception by Non-invasive Vagus Nerve Stimulation: Investigating the Role of GABAergic and Serotonergic Pathways in a Model of Episodic Migraine

Noninvasive vagus nerve stimulation and morphine transiently inhibit trigeminal pain signaling in a chronic headache model

Contact Info

Product

Resources

About