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

Abstract

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.

Upper-Extremity Peripheral Nerve Stimulators

“…7 Central mechanisms also play a role as PNS alters central g-aminobutyric acid-ergic and glycine pathways. 8 Peripheral nerve stimulation leads to a central release of serotonin and dopamine, as measured by their metabolites in cerebrospinal fluid, that may directly decrease the perception of pain. 9 Peripheral nerve stimulation also alters N-methyl-D-aspartateemediated plasticity that may have implications for centrally driven pain sensitization.…”

Neuromodulation for Chronic Daily Headache

“…ONS finds its rationale in the modulation of the trigeminocervical complex [102]. It consists of continuous electrical stimulation of the great occipital nerve through a subcutaneous electrode, which induces paraesthesia in its innervation territory.…”

Effect of Occipital Nerve Stimulation (ONS) on the Orbicularis Oculi Reflex Triggered by a Standardized Air Flow in Patients with Chronic Migraine—A Prospective, Randomized, Interventional Study

“…ONS modulates the responses of the 'trigeminocervical complex' (TCC) neurons to light mechanical input by GABAergic and glycinergic mechanisms. This modulation is mediated by GABAergic and glycinergic mechanisms and can have an inhibitory effect on nociception in the spinal and medullary dorsal horn neurons [9]. In a positron emission tomography (PET) study, ONS stimulation resulted in activation in the dorsal lateral prefrontal cortex, comprising the medial pain pathway, the ventral medial prefrontal cortex, and the bilateral anterior cingulate cortex as well as the parahippocampal area.…”

“…In contrast to the statically triggered orbicularis oculi reflex by electrical stimulation, the triggering of the reflex response by a permanent air flow represents a dynamic reproduction of the natural reflex situation. This can possibly map endogenous pain-modulating processes in the central nervous system by summing them over time and predict therapeutic processes in a more relevant fashion [1,9,13].…”