Greater Occipital Nerve Stimulation Research Articles

Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans.

The existence of a trigeminocervical complex has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of 2 single-blinded, randomised protocols. Forty healthy participants were recruited in the propaedeutic protocol I. Electrical pain thresholds were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online preregistered, and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. Greater occipital nerve stimulation increased the EPT ipsilateral at V1 after 20 minutes (P = 0.006) compared with baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (P = 0.023) as well as the contralateral GON (P = 0.001) after capsaicin application. Protocol II confirmed these results and additionally showed that GON stimulation with capsaicin increased EPTs ipsilateral at all 3 trigeminal dermatomes and that trigeminal stimulation on V1 led to an ipsilateral increase of EPTs at GON, V2, and V3. Our data suggest a strong functional interplay between the trigeminal and occipital system in humans. The fact that the stimulation of one of these dermatomes increases the EPT of the respective other nerve could be explained by segmental inhibition on the brainstem level.

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

BackgroundStimulation 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.MethodsAdult 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.ResultsGON 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.ConclusionsGON 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.

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

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 C2 ganglion neurons. Unmyelinated afferents from GON innervates exclusively laminae I-II of the lateral DH, mostly extending along segments C2-3 . Myelinated fibers distribute mainly in laminae I and III-V of the lateral DH between C1 and C6 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.

Inhibitory effect of high-frequency greater occipital nerve electrical stimulation on trigeminovascular nociceptive processing in rats.

Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons. The experiments were carried out on urethane/chloralose-anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100Hz) and intensity (1, 3, 6V) were tested successively in 10min interval. At all parameter sets, preconditioning GON stimulation (250ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches.

Laser-Evoked Potentials in Fibromyalgia: The Influence of Greater Occipital Nerve Stimulation on Cerebral Pain Processing.

Fibromyalgia causes widespread musculo-skeletal pain in the four quadrants of the body. Greater occipital nerve stimulation has recently shown beneficial effects in fibromyalgia patients on pain, fatigue, and mood disorders. Laser-evoked potentials (LEPs) are used for research to understand the pathophysiological mechanisms of pain and to evaluate the effects of pain treatment. In fibromyalgia patients, LEPs tend to have a higher N2 amplitude, a tendency to shorter latencies, and patients have a lower pain threshold. Greater occipital nerve stimulation might exert a modulation of the medial pain pathways processing the affective motivational components of pain (unpleasantness) as well as the descending pain inhibitory pathways (reducing pain), both of which are contributing to the N2P2 peak. To test this hypothesis, the authors performed LEPs in a group of fibromyalgia patients with and without greater occipital nerve stimulation. Occipital nerve stimulation does not alter the amplitudes of the LEP recordings, although a significant difference in latencies can be seen. More specifically, latencies of the N2P2 increased in the condition after stimulation, and especially at the Pz electrode. Our results suggest Occipital Nerve Stimulation (ONS) induces a modification of the balance between antinociceptive pain inhibitory pathways and pain-provoking pathways.

Occipital Nerve Stimulation for Chronic Migraine

Occipital nerve stimulation may be effective in treating chronic migraine. Six studies, including three double-blind studies, were performed, with five showing evidence of benefit. However, of the three randomized, controlled trials, none has met a primary endpoint successfully. A separate study suggested a benefit for combined supraorbital and greater occipital nerve stimulation.

Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation

Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

Low-Frequency Short-Time Nociceptive Stimulation of the Greater Occipital Nerve does not Modulate the Trigeminal System

Occipital stimulation in a small group of refractory chronic migraine and cluster headache patients has been suggested as a novel therapeutic approach with promising results. In an earlier study we have shown that a drug-induced block of the greater occipital nerve (GON) inhibits the nociceptive blink reflex (nBR). Now, we sought to examine the effects of low-frequency (3 Hz) short-time nociceptive stimulation of the GON on the trigeminal system. We recorded the nBR responses before and after stimulation in 34 healthy subjects. Selectivity of GON stimulation was confirmed by eliciting somatosensory evoked potentials of the GON upon stimulation. In contrast to an anaesthetic block of the occipital nerve, no significant changes of the R2-latencies and R2-response areas of the nBR can be elicited following GON stimulation. Various modes of electrical stimulation exist with differences in frequency, stimulus intensity, duration of stimulation and pulse width. One explanation for a missing modulatory effect in our study is the relatively short duration of the stimulation.

Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input.

Patients with primary headaches often report pain that involves not only the front of the head, innervated by the first (ophthalmic) division of the trigeminal nerve, but also the back of the head, innervated by the greater occipital nerve (GON) that is a branch of the C(2) spinal root. The aim of this work was to study the physiology of trigeminocervical input in a model of cranial nociception by describing a population of nociceptive neurones that receive convergent input from the supratentorial dura and the GON. Rats were anaesthetized with pentobarbital, paralysed and ventilated. The parietal dura above the middle meningeal artery was stimulated through a closed cranial window. The GON was exposed in the neck and stimulated. Recordings were made from 67 neurones (52 wide dynamic range neurones/15 nociceptive-specific-neurones) in the C(2) spinal dorsal horn, which responded to stimulation of the dura and the GON. Most neurones showed receptive fields corresponding to the first trigeminal division as well as input from C(2) skin and muscle. Neurones were recorded in superficial and deep layers of the dorsal horn. All neurones tested received input from the ipsilateral and contralateral GON (n = 5). The responses to dural stimulation were analysed before and after stimulation of the GON. Supramaximal electrical stimulation of the GON (20 s to 5 min) enhanced afferent dural input in 8/20 neurones. Application of the C-fibre activator mustard oil (MO) to the cutaneous receptive field or suboccipital muscles innervated by the GON induced an increased excitability of dural responses in 8/12 and 9/10 neurones, respectively. Stimulation of muscle afferents had a significant longer facilitatory effect than cutaneous stimulation (P < 0.05). These results show that a considerable population of neurones show convergent input from both dura as well as cervical cutaneous and muscle territories, which supports the view of a functional continuum between the caudal trigeminal nucleus and upper cervical segments involved in cranial nociception. The facilitatory effect of GON stimulation on dural stimulation suggests a central mechanism at the second order neurone level. This mechanism may be important in pain referral from cervical structures to the head and therefore have implications for most forms of primary headache.

外傷性頸部症候群発症のメカニズムに関する電気生理学的考察

In order to elucidate the mechanism of the traumatic cervical syndrome, electrophysiological studies were conducted in rabbits. The greater occipital nerve (GON), cervical sympathetic trunk (SYMP) or both GON and SYMP (BOTH) was stimulated electrically with frequencies of the 3 Hz or 100 Hz. And diazepam (2-5 mg/kg) and pentazocine (3-6 mg/kg) were administered to observe the effect of these drugs on the cervical syndrome. The following was observed.1) The threshold of arousal reaction and the evoked muscular discharge due to stimulation of the brain stem reticular formation increased. The change with 100 Hz stimulation was more pronounced than with 3 Hz stimulation. The change in the arousal reaction was more pronounced than that of the evoked muscular discharge. The threshold changes were inhibited following administration of diazepam but not greatly inhibited by administration of pentazocine.2) The threshold of the evoked muscular discharge due to stimulation of t he cerebral cortex rose. The change was more prominent when BOTH was stimulated, and was inhibited following administration of diazepam.3) The threshold of the evoked muscular discharge due to stimulation of the hippocampus declined. The change with 3 Hz stimulation of SYMP was more marked than with 100 Hz stimulation of the SYMP, and was inhibited following administration of diazepam.4) The amplitude of the recruiting response due to stimulation of the VA with frequency of 8 Hz, increased markedly. This change disappeared following administration of diazepam, but was reversed following administration of pentazocine.5) The amplitude of the photo-evoked eyelid microvibration (MV) either increased or decreased. These changes were more prominent when SYMP was stimulated. In the cases of inhibition, the change due to GON stimulation alone was inhibited following administration of diazepam. In the cases of facilitation, diazepam had an effect on the change due to GON, SYMP or BOTH stimulation. Pentazocine had no effect in any of the cases.6) The amplitude of the sciatic evoked eyelid microvibration (SMV) increased. This change disappeared following administration of diazepam, and was inhibited following administration of pentazocine 6 mg/kg.7) The amplitu de of the nociceptive reflex decreased. The change due to GON or SYMP stimulation was inhibited following administration of diazepam, but pentazocine had no effect.8) The blood flow volume of the carotid and subclavicular arteries decreased with SYMP and BOTH stimulation, but that by GON stimulation remained almost unchanged. This change was inhibited following administration of diazepam, but was no affected by administration of pentazocine.9) Intestinal movement decreased by stimulation of these nerves. Diazepam inhibited this change markedly but pentazocine did not.10) In order to clarify the mechanis m of the above changes, VA and hippocampus were destroyed, and vagotomy was performed.The inhibition of, the arousal reaction and evoked muscular discharge due to stimulation of the brain stem reticular formation; evoked muscular discharge due to stimulation of the cerebral cortex; MV; and nociceptive reflex; all disappeared after VA destruction. The facilitation of, the evoked muscular discharge due to stimulation of the hippocampus; MV; and SMV; all disappeared after the widespread destruction of the hippocampus. The inhibition of intestinal movement did not disappear after vagotomy of both sides.