Occipital Nerve Stimulation Attenuates Neuronal Firing Response to Mechanical Stimuli in the Ventral Posteromedial Thalamus of a Rodent Model of Chronic Migraine

Walling, Ian; Smith, Heather; Gee, Lucy; Kaszuba, Brian C.; Chockalingam, Arun; Barborică, Andrei; Donos, Cristian; Shin, Damian S.; Pilitsis, Julie G.

doi:10.1093/neuros/nyx135

Cited by 14 publications

(13 citation statements)

References 26 publications

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“…So far, only a few acute and short‐term studies are available in rats, that indicate that GON stimulation induces lasting elevations of mechanical (but not thermal) thresholds in the forepaw and periorbital region (De La Cruz et al, ), and decreases spontaneous activity and responsivity to receptive field stimulation of neurons in laminae II‐IV neurons of the medullary DH that receive converging input from the supra‐ and/or infraorbital skin, the supratentorial dura, and the GON (Lyubashina et al, ). A neuromodulatory effect of GON stimulation has also been reported on thalamic neurons upstream the trigeminal somatosensory pathways, which become sensitized in a migraine model, but reduce their spontaneous and facial and forepaw mechanical stimulation‐evoked activity during GON stimulation (Walling et al, ).…”

Section: Discussionmentioning

confidence: 96%

“…The GON has recently become a useful target for testing how its block or stimulation in a rat model of migraine affects mechanical and nociceptive thresholds in the head and elsewhere (De La Cruz et al, ; Walling et al, ), and alters trigeminovascular nociceptive processing in the spinal trigeminal nucleus (Lyubashina, Panteleev & Sokolov, ). However, available data on the GON anatomy and connections in the rat is scanty, being limited to two early studies using HRP transport (Neuhuber & Zenker, ; Scheurer, Gottschall & Groh, ).…”

Section: Introductionmentioning

confidence: 99%

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The greater occipital nerve and its spinal and brainstem afferent projections: A stereological and tract‐tracing study in the rat

García-Magro

Martín

Negredo

et al. 2018

J of Comparative Neurology

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The neuromodulation of the greater occipital nerve (GON) has proved effective to treat chronic refractory neurovascular headaches, in particular migraine and cluster headache. Moreover, animal studies have shown convergence of cervical and trigeminal afferents on the same territories of the upper cervical and lower medullary dorsal horn (DH), the so-called trigeminocervical complex (TCC), and recent studies in rat models of migraine and craniofacial neuropathy have shown that GON block or stimulation alter nociceptive processing in TCC. The present study examines in detail the anatomy of GON and its central projections in the rat applying different tracers to the nerve and quantifying its ultrastructure, the ganglion neurons subserving GON, and their innervation territories in the spinal cord and brainstem. With considerable intersubject variability in size, GON contains on average 900 myelinated and 3,300 unmyelinated axons, more than 90% of which emerge from C ganglion neurons. Unmyelinated afferents from GON innervates exclusively laminae I-II of the lateral DH, mostly extending along segments C . Myelinated fibers distribute mainly in laminae I and III-V of the lateral DH between C and C and, with different terminal patterns, in medial parts of the DH at upper cervical segments, and ventrolateral rostral cuneate, paratrigeminal, and marginal part of the spinal caudal and interpolar nuclei. Sparse projections also appear in other locations nearby. These findings will help to better understand the bases of sensory convergence on spinomedullary systems, a critical pathophysiological factor for pain referral and spread in severe painful craniofacial disorders.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

The greater occipital nerve and its spinal and brainstem afferent projections: A stereological and tract‐tracing study in the rat

García-Magro

Martín

Negredo

et al. 2018

J of Comparative Neurology

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“…The global pharmacological blockade of NMDA, GABA and/or Glycine receptors in the TCC, particularly in its super cial laminae, was attempted by local infusion of speci c receptor antagonists. Amino-5phosphonovaleric acid or (AP-5, a NMDA receptor antagonist, 50 µM), Bicuculline methiodide (Bic, a GABA A receptor antagonist, 20 mM), Strychnine (Str, an antagonist of the Glycine receptor, 100 µM), or a mixture of Str and Bic were mechanically delivered over the TCC through a glass micropipette (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) mm tip outer diameter) attached to a 10 μl Hamilton syringe. The injected volume was 2 µl.…”

Section: Drug Applicationmentioning

confidence: 99%

“…It was rst shown in rats that the neurons in the caudal part of the TCC displayed crossed sensitization and functional coupling to input from nociceptive supratentorial dural afferents, which course along the trigeminal nerve, and cervical afferents conveyed through the GON [19,28]. However, in a rat model of migraine GON electrostimulation induced lasting elevations of mechanical allodynia thresholds at trigeminal and other bodily regions [29], and reduced tonic and burst ring of ventroposteromedial thalamic neurons in response to mechanosensory stimuli [30].…”

mentioning

confidence: 99%

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

García-Magro

Negredo

Martín

et al. 2020

Preprint

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Background: Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.Methods: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally.Results: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.Conclusions: GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.

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“…It was first shown in rats that the neurons in the caudal part of the TCC displayed crossed sensitization and functional coupling to input from nociceptive supratentorial dural afferents, which course along the trigeminal nerve, and cervical afferents conveyed through the GON [19,28]. However, in a rat model of migraine GON electrostimulation induced lasting elevations of mechanical allodynia thresholds at trigeminal and other bodily regions [29], and reduced tonic and burst firing of ventroposteromedial thalamic neurons in response to mechanosensory stimuli [30].…”

Section: Introductionmentioning

confidence: 99%

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

et al. 2020

View full text Add to dashboard Cite

Background: Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the 'trigeminocervical complex' (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad. Methods: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABA A (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally. Results: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.

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Occipital Nerve Stimulation Attenuates Neuronal Firing Response to Mechanical Stimuli in the Ventral Posteromedial Thalamus of a Rodent Model of Chronic Migraine

Abstract: We demonstrate that neuronal spike frequencies and bursting activity in the VPM are increased in an animal model of CM compared to shams. Our results suggest that the mechanism of ONS may involve attenuation of neurons in the VPM of CM rats during the application of mechanical stimuli.

Cited by 14 publications

References 26 publications

The greater occipital nerve and its spinal and brainstem afferent projections: A stereological and tract‐tracing study in the rat

The greater occipital nerve and its spinal and brainstem afferent projections: A stereological and tract‐tracing study in the rat

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

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