Pulsed Radiofrequency of the Trigeminal Ganglion for Treating Postherpetic Neuralgia of the Ophthalmic Branch.

Postherpetic neuralgia (PHN) is a painful, long-lasting condition as a consequence of nerve damage resulting from a herpes zoster infection. Although there are many different treatments available to reduce pain duration and severity, PHN is often refractory to them and no single therapy shows an effective cure for all cases of PHN, especially for those involving the ophthalmic branch of the trigeminal nerve. Pulsed radiofrequency (PRF) is a minimally invasive procedure for pain treatment that has been practiced over the past decade. However, its clinical efficacy and safety for treating PHN involving the ophthalmic branch of the trigeminal nerve have not been evaluated. Objective. This study aimed to evaluate the efficacy and safety of PRF for treating PHN involving the ophthalmic branch of the trigeminal ganglion. Study Design. An observational study. Setting. All patients received PRF of the ophthalmic branch of the trigeminal nerve, pain intensity was assessed by a visual analogue scale (VAS), and complications before and after PRF stimulation were noted. Methods. Thirty-two patients with PHN of the ophthalmic branch were treated by PRF of the ophthalmic branch with controlled temperature at 42°C for 8 min. Pain relief, corneal reflex, sleep quality, and satisfaction were assessed for all patients. Results. Thirty out of 32 patients (93.75%) reported significant pain reduction after PRF treatment. Twenty-eight of them (87.5%) were satisfied with their sleep and obtained a pain score lower than 3 following the procedure. Only two patients had a recurrence of the severe burning pain and returned to the hospital for other medical therapies 2 weeks after the PRF procedure. No patient lost the corneal reflex. Limitations. This study is an observational study and a nonprospective trial with a short-term follow-up period. Conclusion. PRF of the trigeminal ganglion of the ophthalmic branch can significantly reduce pain sensation and improve sleep quality and satisfaction for PHN of the ophthalmic branch.

Effect of non-thermal radiofrequency on body temperature in mice.

Communication technologies based on radiofrequency (RF) propagation bring great benefits to our daily life. However, their rapid expansion raises concerns about possible impacts on public health. At intensity levels below the threshold to produce thermal effects, RF exposure has also recently been reported to elicit biological effects, resembling reactions to cold. The objective of the present study was to investigate the effects of non-thermal RF on body temperature in mice and the related mechanisms. 3-months-old C57BL/6 J mice were exposed to a continuous RF signal at 900 MHz, 20 ± 5 V.m-1 for 7 consecutive days, twice per day during the light phase, for one hour each time. The SAR was 0.16 ± 0.10 W.kg-1. We showed that body temperature patterns in mice change synchronously with the RF exposure periods. Average body temperature in the light phase in the exposed group was higher than in the control group. The expression of the TRPM8 gene was not affected by RF in trigeminal ganglia. Furthermore, the injection of a TRPM8 antagonist did not induce a temperature decrease in exposed mice, as this was the case for sham-controls. These findings indicate that 900 MHz RF exposure at non-thermal level produce a physiological effect on body temperature in mice. However, the involvement of TRPM8 receptors in the mechanism by which RF induced changes in body temperature of mice which remains to be further explored. It must then be assessed if this effect is extrapolable to man, and if this could lead to consequences on health.

Blue light exposure in vitro causes toxicity to trigeminal neurons and glia through increased superoxide and hydrogen peroxide generation.

Today the noxiousness of blue light from natural and particularly artificial (fluorescent tubes, LED panels, visual displays) sources is actively discussed in the context of various ocular diseases. Many of them have an important neurologic component and are associated with ocular pain. This neuropathic signal is provided by nociceptive neurons from trigeminal ganglia. However, the phototoxicity of blue light on trigeminal neurons has not been explored so far. The aim of the present in vitro study was to investigate the cytotoxic impact of various wavebands of visible light (410-630 nm) on primary cell culture of mouse trigeminal neural and glial cells. Three-hour exposure to narrow wavebands of blue light centered at 410, 440 and 480 nm of average 1.1 mW/cm2 irradiance provoked cell death, altered cell morphology and induced oxidative stress and inflammation. These effects were not observed for other tested visible wavebands. We observed that neurons and glial cells processed the light signal in different manner, in terms of resulting superoxide and hydrogen peroxide generation, inflammatory biomarkers expression and phototoxic mitochondrial damage. We analyzed the pathways of photic signal reception, and we proposed that, in trigeminal cells, in addition to widely known mitochondria-mediated light absorption, light could be received by means of non-visual opsins, melanopsin (opn4) and neuropsin (opn5). We also investigated the mechanisms underlying the observed phototoxicity, further suggesting an important role of the endoplasmic reticulum in neuronal transmission of blue-light-toxic message. Taken together, our results give some insight into circuit of tangled pain and photosensitivity frequently observed in patients consulting for these ocular symptoms.

Neurochemical effects of photobiostimulation in the trigeminal ganglion after inferior alveolar nerve injury.

Orofacial pain is associated with peripheral and central sensitization of trigeminal nociceptive neurons. Nerve injury results in release of chemical mediators that contribute to persistent pain conditions. The activation of the transient receptor potential vanilloid 1 (TRPV1), promotes release of calcitonin gene-related peptide (CGRP) and substance P (SP) from trigeminal nerve terminals. CGRP and SP contribute to the development of peripheral hyperalgesia. The expression of SP and CGRP by primary afferent neurons is rapidly increased in response to peripheral inflammation. CGRP receptor activation promotes activation of AMPA receptors, leading to increased firing of neurons which is reflected as central sensitization. In this study we investigated whether inferior alveolar nerve (IAN) injury influences AMPA receptors, CGRP, SP and TRPV1 expression in the trigeminal ganglion (TG). The relative expression of the protein of interest from naive rats was compared to those from injured rats and animals that received low level laser therapy (LLLT). IAN-injury did not change expression of GluA1, GluA2 and CGRP, but increased the expression of TRPV1 and SP. LLLT increases GluA1 and GluA2 expression and decreases TVPV1, SP and CGRP. These results, together with previous behavioral data, suggest that IAN-injury induced changes in the proteins analyzed, which could impact on nociceptive threshold. These data may help to understand the molecular mechanisms of pain sensitization in the TG.

[Exclusive radiotherapy for a facial basal cell carcinoma with trigeminal ganglion involvement]. / Radiothérapie exclusive d'un carcinome basocellulaire de la face avec atteinte du ganglion de Gasser.

Basal cell carcinomas with symptomatic perineural invasion are rare entities. We report the case of a 60year-old man (with a grafted kidney), surgically treated in 2007 for a sclerodermiform basal cell carcinoma infiltrating the left nostril. Five years later, a painful left hemifacial hypoesthesia associated with an ulcus rodens of the nasolabial fold appeared. A biopsy confirmed a recurrence. MRI showed an enhancement of the trigeminal ganglion. The patient had a trigeminal perineural invasion secondary to a cutaneous basal cell carcinoma. He received a local intensity-modulated radiotherapy alone (70Gy in 33 sessions), administered from the skin tumour to the skull base. Three years after the end of treatment, the patient is in radiological and clinical remission, with partial recovery of the hypoesthesia. Evolution was marked by iterative corneal ulcers and decreased visual acuity. Modalities of treatment by surgery and/or radiation therapy and complications are poorly described in the literature.

Light-activated serotonin for exploring its action in biological systems.

Serotonin (5-HT) is a neuromodulator involved in regulating mood, appetite, memory, learning, pain, and establishment of left-right (LR) asymmetry in embryonic development. To explore the role of 5-HT in physiology, we have created two forms of "caged" 5-HT, BHQ-O-5HT and BHQ-N-5HT. When exposed to 365 or 740 nm light, BHQ-O-5HT releases 5-HT through one- or two-photon excitation, respectively. BHQ-O-5HT mediated changes in neural activity in cultured mouse primary sensory neurons and the trigeminal ganglion and optic tectum of intact zebrafish larvae in the form of high-amplitude spiking in response to light. In Xenopus laevis embryos, light-activated 5-HT increased the occurrence of LR patterning defects. Maximal rates of LR defects were observed when 5-HT was released at stage 5 compared with stage 8. These experiments show the potential for BHQ-caged serotonins in studying 5-HT-regulated physiological processes.

Bright light activates a trigeminal nociceptive pathway.

Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.

Chronic electrostimulation of the trigeminal ganglion in trigeminal neuropathy: current state and future prospects.

Over two decades ago, the electrostimulation of the trigeminal ganglion (TGES) was established as a treatment option for patients with trigeminopathic pain due to a (iatrogenic) lesion of the trigeminal nerve, on whom the other therapeutic methods, either neurosurgical or conservative have very limited efficacy and usually are associated with a poor outcome. The technique of TGES which uses the setup also used for the thermocoagulation lesion for trigeminal neuralgia was first published by Steude in 1984 and has not been altered substantially. After a percutaneous puncture with a 16 gage needle of the oval foramen, a monopolar electrode (diameter 0.9mm, custom-made) is placed in the postganglionic trigeminal nerve. After a successful test-stimulation phase, a permanent electrode pulse generator system is implanted. Our experience includes more than 300 patients with a minimum follow-up of one year. Of these patients, 52% showed a good to excellent analgesic effect. The TGES-induced analgesia was persistent in long term-follow-up in all patients. The impact of TGES on cerebral pain modulation was proven by electrophysiology and PET. TGES is an effective, minimally invasive and reversible treatment option in selected patients with trigeminopathic pain; it should, therefore, always be considered as the primary treatment-option. Electrodes with two leads and a diameter not exceeding the 0.9 mm, allowing bipolar stimulation might enhance the neuromodulatory efficacy and options of TGES.

Multisensory integration in the dorsal cochlear nucleus: unit responses to acoustic and trigeminal ganglion stimulation.

A necessary requirement for multisensory integration is the convergence of pathways from different senses. The dorsal cochlear nucleus (DCN) receives auditory input directly via the VIIIth nerve and somatosensory input indirectly from the Vth nerve via granule cells. Multisensory integration may occur in DCN cells that receive both trigeminal and auditory nerve input, such as the fusiform cell. We investigated trigeminal system influences on guinea pig DCN cells by stimulating the trigeminal ganglion while recording spontaneous and sound-driven activity from DCN neurons. A bipolar stimulating electrode was placed into the trigeminal ganglion of anesthetized guinea pigs using stereotaxic co-ordinates. Electrical stimuli were applied as bipolar pulses (100 micros per phase) with amplitudes ranging from 10 to 100 microA. Responses from DCN units were obtained using a 16-channel, four-shank electrode. Current pulses were presented alone or preceding 100- or 200-ms broadband noise (BBN) bursts. Thirty percent of DCN units showed either excitatory, inhibitory or excitatory-inhibitory responses to trigeminal ganglion stimulation. When paired with BBN stimulation, trigeminal stimulation suppressed or facilitated the firing rate in response to BBN in 78% of units, reflecting multisensory integration. Pulses preceding the acoustic stimuli by as much as 95 ms were able to alter responses to BBN. Bimodal suppression may play a role in attenuating body-generated sounds, such as vocalization or respiration, whereas bimodal enhancement may serve to direct attention in low signal-to-noise environments.

Kynurenine aminotransferase in the supratentorial dura mater of the rat: effect of stimulation of the trigeminal ganglion.

Electrical stimulation of the trigeminal ganglion has been widely used as a model of nociception, characterizing migraine. This treatment is known to evoke release of neuropeptides and neurotransmitters from nerve fibers of the dura mater. On the basis of immunocytochemical investigations, we found that under normal conditions, surface membranes of Schwann cells surrounding nerve fibers in the supratentorial dura mater display kynurenine aminotransferase-immunoreaction (KAT-IR); also KAT-IR are the granules of mast cells and the cytoplasms of macrophages (histiocytes). In consequence of stimulation of the trigeminal ganglion, Schwann cells in the dura mater became conspicuously swollen while their KAT-IR decreased considerably; also KAT-IR of mast cells and macrophages decreased significantly. At the same time, nitric oxide synthase (NOS)-IR of nerve fibers in the dura mater increased, suggesting release of nitric oxide (NO), this is known to be involved in NMDA receptor activation leading to vasodilation followed by neurogenic inflammation. Because kynurenic acid (KYNA) is an antagonist of NMDA receptors, we hypothesize that KYNA and its synthesizing enzyme, KAT, may play a role in the prevention of migraine attacks.

[The study of effects of static magnetic field on SP-mRNA in trigeminal ganglion in rats].

OBJECTIVE: To evaluate the effect of static magnetic field on the expression of SP-mRNA in TG in rats. METHODS: 44 Wistar rats aged 6-7 weeks were put into static magnetic field and were sacrificed at 1 h, 2 h, 6 h, 12 h, 24 h, respectively. In situ hybridization method was used to evaluate the changes of SP-mRNA expression at different time point. RESULTS: Many neurons in TG were marked with SP probes in each group, the expression of SP-mRNA increased remarkably in static magnetic field group. In this group, the percentage of SP-mRNA positive neurons in TG increased greatly in 1 h, reached its peak in 2 h, from then on, decrease of the percentage started slowly but a moderate percentage was kept until 24 h, which was thought to be enough to maintain orthodontic tooth movement. The tendency of control group was almost the same with that of experimental group. The expression of SP-mRNA was higher in experimental group within 2 h but became lower after 2 h as compared with control group, this indicated that magnetic field reduced the SP-mRNA expression and exerted restoring effect on trauma. There were significant differences between experimental groups and control group at different time points (P < 0.01). CONCLUSION: The expression of SP-mRNA in TG in rats increased significantly in static magnetic field.

A prospective, longitudinal study on patients with trigeminal neuralgia who underwent radiofrequency thermocoagulation of the Gasserian ganglion.

Outcome after radiofrequency thermocoagulation in patients with trigeminal neuralgia was assessed in a prospective, longitudinal study. Forty-eight consecutive patients with chronic facial pain presenting for surgery to a neurosurgeon were studied. Patients were assessed preoperatively by an independent clinician both clinically, and with the use of two questionnaires: the McGill Pain Questionnaire (MPQ) and the Hospital Anxiety and Depression (HAD) scale. From these assessments, two groups of patients were identified: 31 with pure trigeminal neuralgia (TN group) and 17 with trigeminal neuralgia together with atypical facial pain and mixed trigeminal neuralgia (MTN group). All underwent radiofrequency thermocoagulation at the level of the Gasserian ganglion. Patients were reviewed by the same clinician 3 months later and then followed up by a self-administered questionnaire at 6 months, 1 year, 2 years and 3 years. The mean follow-up time was 30+/-12 months. The mean time to recurrence of pain was 40 months for the TN group and 36 months for the MTN group. Depression and anxiety dropped more significantly post-operatively in the TN group than the MTN group. TN group were more satisfied with their outcome, complained of fewer complications and were more willing to have repeat surgery if necessary than patients in MTN group. The number and severity of complications varied at different time points. Careful selection of patients for surgery using objective assessments will decrease morbidity and improve satisfaction. Physical morbidity and recurrence rates are insufficient to gauge outcomes. Psychological, sociological and patients' views must be included in evaluations.

Effects of gamma-irradiation on embryonic development and nucleic acids in trigeminal neurons.

Pregnant rats were exposed to absorbed doses of 0.5, 1, 2, and 4 Gy of 60Co-gamma rays either on day 8 or on day 12 p.c.. The embryos were collected on day 18 p.c.. Irradiations both on day 8 and 12 p.c. result in a dose dependent decrement of weight. The effect is larger for irradiation on day 8 p.c.. Caryometric studies of the neurons in the trigeminal ganglion show, on the other hand, that the reduction of nuclear sizes in this tissue is more substantial for an irradiation on day 12 p.c. when the ganglion is in a stage of formation. Cytophotometric determinations of the Feulgen-DNA content and determination of the RNA content by staining and chromic gallocyanin in combination with ribinuclease digestion lead to the conclusion that the irradiation induces no significant hyperploidy and that the irradiated neurons have the nuclear RNA content that is normal at this stage of gestation. This applies both to the irradiations on day 8 and on day 12 p.c.