Long-term pain relief at five years after medical, repeat surgical procedures or no management for recurrence of trigeminal neuralgia after microvascular decompression: analysis of a historical cohort.

BACKGROUND: Management strategies for the recurrence of trigeminal neuralgia after microvascular decompression include repeat procedures, medical management or no further therapy. No consensus exists as to which strategy is best for pain relief. The aim of this study was to determine the characteristics of patients with recurrences after microvascular decompression in the cohort, and to compare long-term pain relief between different management strategies. MATERIALS AND METHODS: A historical cohort of patients who underwent microvascular decompression at a neurosurgical institution between 1982-2002, followed up by postal survey at five years, was included. Characteristics of patients who experienced a recurrence were compared to those who were recurrence free, and pain relief was compared between each management strategy. RESULTS: From 169 responders who were included in the study, 28 (16.6%) experienced a recurrence after MVD. No characteristics were significantly different between patients who experienced a recurrence and those who did not. Repeat procedures, including repeat microvascular decompression, partial sensory rhizotomy or radiofrequency thermocoagulation, yielded the highest proportion of pain relief after recurrence (p = 0.031), with 63.6% of patients pain-free at five-years. There was no evidence to suggest that the choice of repeat procedure influenced the likelihood of pain relief after recurrence. No further treatment yielded 57.1% pain-free, whereas medical therapy had the lowest proportion of pain-free patients, at 10.0%. CONCLUSION: A variety of options are available to patients for recurrence of TN after microvascular decompression with repeat procedures yielding the greatest likelihood of long-term pain relief in this historical cohort. The choice of management should consider the mechanism of recurrence, the benefits and risks of each option and the severity of the pain. Regardless of the management strategy selected, careful phenotyping of patients before and after surgery is paramount.

Utility of Brainstem Trigeminal Evoked Potentials in Patients With Primary Trigeminal Neuralgia Treated by Microvascular Decompression.

OBJECTIVE: To investigate the characteristics of brainstem trigeminal evoked potentials (BTEP) waveform in patients with and without trigeminal neuralgia (TN), and to discuss the utility of BTEP in patients with primary TN treated by microvascular decompression (MVD). METHODS: A retrospective review of 43 patients who underwent BTEP between January 2016 and June 2016, including 33 patients with TN who underwent MVD and 10 patients without TN. Brainstem trigeminal evoked potentials characteristics of TN and non-TN were summarized, in particular to compare the BTEP changes between pre- and post-MVD, and to discover the relationship between BTEP changes and surgical outcome. RESULTS: Brainstem trigeminal evoked potentials can be recorded in patients without trigeminal neuralgia. Abnormal BTEP could be recorded when different branches were stimulated. After decompression, the original W2, W3 disappeared and then replaced by a large wave in most patients, or original wave poorly differentiated improved in some patients, showed as shorter latency and (or) amplitude increased. Brainstem trigeminal evoked potentials waveform of healthy side in patients with trigeminal neuralgia was similar to the waveform of patients without TN. In 3 patients, after decompression the W2, W3 peaks increased, and the latency, duration, IPLD did not change significantly. Until discharge, 87.9% (29/33) of the patients presented complete absence of pain without medication (BNI I) and 93.9% (31/33) had good pain control without medication (BNI I-II). CONCLUSION: Brainstem trigeminal evoked potentials can reflect the conduction function of the trigeminal nerve to evaluate the functional level of the trigeminal nerve conduction pathway. The improvement and restoration of BTEP waveforms are closely related to the postoperative curative effect.

Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

AIMS: To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. METHODS: Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. RESULTS: Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. CONCLUSION: Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

The role of percutaneous balloon compression in the treatment of trigeminal neuralgia recurring after other surgical procedures.

Trigeminal neuralgia (TN) recurring after surgery can be difficult to treat. Treatment algorithms have not been standardized or universally accepted. Here we investigated the effectiveness of percutaneous balloon compression (PBC) in the treatment of patients with TN recurrence after other surgical techniques and analyzed the role of some clinical and operative factors in determining the prognosis. The records of 22 patients (13 M and 9 F) suffering recurrent TN after one (2 gamma knife surgery, 5 percutaneous radiofrequency rhizotomy, 6 percutaneous retrogasserian glycerol rhizotomy, 3 microvascular decompression) or more (6 patients) procedures and submitted to PBC at our institution from January 2003 to February 2012 were reviewed. Seven patients had TN related to multiple sclerosis (MS). Mean follow-up was 51.81 ± 26.63 months. 81.81 % of patients reported an acute pain relief. No major complication was observed after PBC. Eight patients (36.36 %) experienced pain recurrence and underwent one (five patients) or more (three patients) PBC. At the last follow-up, we obtained an excellent outcome (BNI I-II) in 16 patients out of 22 (72.72 %) and a good outcome (BNI III) in the remaining six. No patients had an uncontrolled pain. The lack of history of MS (p = 0.0174), the pear-like shape of the balloon at the operation (p = 0.0234) and a compression time <5 min (p < 0.05) were associated to higher pain-free survival. Considering these results PBC could be considered a useful technique for patients whose pain recurs after other procedures.

Evaluation of a novel mouse model of intracisternal strychnine-induced trigeminal allodynia.

PURPOSE: Intractable neuropathic dynamic allodynia remains one of the major symptoms of human trigeminal neuropathy and is commonly accepted to be the most excruciatingly painful condition known to humankind. At present, a validated animal model of this disorder is necessary for efficient and effective development of novel drug treatments. Intracisternal strychnine in rats has been shown to result in localized trigeminal dynamic allodynia, thus representing a possible model of trigeminal neuralgia. The purpose of this study was to validate a mouse model of trigeminal glycinergic inhibitory dysfunction using established positive (carbamazepine epoxide) and negative (morphine) controls. METHODS: The actions of conventional first-line treatment (carbamazepine epoxide [CBZe]) and clinically ineffective morphine were tested for trigeminal dynamic mechanical allodynia produced by intracisternal strychnine. In mice under halothane anesthesia, we injected either strychnine (0.3 µg), strychnine with CBZe (4 ng), or artificial cerebrospinal fluid (aCSF) intracisternally (i.c.). In a separate set of experiments, subcutaneous morphine (3 mg·kg(-1) sc) was injected with intracisternal strychnine. Dynamic mechanical allodynia was induced by stroking the fur with polyethylene (PE-10) tubing. The response of each mouse was rated to determine its allodynia score, and scores of each group were compared. In addition, in a separate dichotomous disequilibrium study, pairs of mice were injected with strychnine/saline, strychnine/strychnine-CBZe, or strychnine/strychnine-morphine. A blinded observer recorded which mouse of each pair had the greater global pain behaviour. RESULTS: Strychnine (i.c.) produced higher quantitative allodynia scores in the trigeminal distribution (mean 81.5%; 95% confidence interval [CI] 76.4 to 86.6) vs the aCSF group (mean 11.3%; 95% CI 8.1 to 14.4) (P < 0.0001). Carbamazepine epoxide (i.c.) completely abolished allodynia when co-injected with strychnine (mean 83.2%; 95% CI 78.1 to 88.4) vs strychnine alone (mean 3.2%; 95% CI -0.9 to 7.2) (P < 0.0001). Morphine co-injected with strychnine did not result in reduced allodynia (mean 65.7%; 95% CI 42.0 to 89.4) compared with strychnine alone (mean 87.6%; 95% CI 77.6 to 97.6) (P = 0.16). In a further global allodynia assessment, strychnine (i.c.) produced greater allodynia than both aCSF and strychnine administered with CBZe (P = 0.03). Morphine (ip) administered with strychnine did not result in reduced global allodynia compared with strychnine administered alone (P = 1.0). CONCLUSION: In this study, we have developed and validated a novel murine model of trigeminal dynamic allodynia induced by intracisternal strychnine. The use of mice to study trigeminal allodynia has many benefits, including access to a vast repository of transgenic mouse variants, ease of handling, low cost, and minimal variance of results. The present model may have utility in screening drug treatments for dynamic mechanical allodynia resulting from trigeminal neuropathies.

Effectiveness of repeat glycerol rhizotomy in treating recurrent trigeminal neuralgia.

BACKGROUND: Percutaneous glycerol rhizotomy (GR) is used to treat trigeminal neuralgia (TN), with satisfactory pain relief lasting 2 to 3 years in most patients after the first intervention. The efficacy of subsequent GRs, however, has not been studied. OBJECTIVE: To compare the pain relief and durability achieved by the first GR with those obtained after subsequent GRs in a retrospective cohort of TN patients. METHODS: Between 1998 and 2010, 548 patients with TN underwent 708 GRs. After exclusions, 430 initial GRs (GR1) and 114 subsequent GRs (GR2+) were compared in terms of initial pain relief, durability, sensory change, and complications. Durability was assessed by determining median time to treatment failure for all GRs achieving complete pain relief without medications (n = 375: 264 failures, 111 censored). Predictors of initial pain relief were assessed by logistic regression, and predictors of failure were assessed by Cox regression analysis. RESULTS: After GR1, pain relief results were as follows: 285 patients (66%) were pain free without medications, 26 (6%) were pain free with medications, 66 (15%) improved, and 53 (12%) were unchanged. After GR2+, results were as follows: 90 patients (79%) were pain free without medications, 6 (5%) were pain free with medications, 7 (6%) improved, and 11 (10%) were unchanged (P = .03). Median time to treatment failure was 26 months after GR1 and 25 months after GR2+ (P = .34). On multivariate analysis, prior GR was a positive predictor of initial pain relief (odds ratio, 2.067; 95% confidence interval, 1.243-3.437; P = .005) and had no effect on durability. CONCLUSION: TN patients experienced greater pain relief and equivalent durability after GR2+ beyond the initial treatment.

Identifying the trigeminal nerve branches for transovale radiofrequency thermolesion: "no pain, no stress".

BACKGROUND: Radiofrequency thermorhizotomy of the trigeminal nerve is a known treatment of trigeminal neuralgia. Analysis of verbal responses to electric stimulation of the trigeminal rootlets has been the only method available to localize the affected branch, but patient discomfort may lead to unreliable verbal responses, resulting in increased morbidity or even therapeutic failure. Orthodromically elicited evoked potentials of the trigeminal nerve have also been used, but their application is tedious and results may vary. OBJECTIVE: To develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches. METHODS: A series of 55 patients under general anesthesia during radiofrequency thermorhizotomy were studied. The trigeminal nerve root was stimulated through the foramen ovale with the RF electrode. Antidromic responses were recorded from the 3 divisions of the trigeminal nerve in the face. Effectiveness rate, pain relief, recurrence, complications, and patient comfort after the procedure were analyzed. RESULTS: Reproducible and easily obtained antidromic responses were clearly recorded in every subdivision of the trigeminal nerve in all patients. Ninety-four percent of patients experienced immediate pain relief after the procedure. The recurrence rate was 12.72%, and the surgical morbidity was 20%. CONCLUSION: This method proved to be useful to determine the exact localization of individual subdivisions of the trigeminal nerve in anesthetized patients, making this procedure safer and more comfortable for them.

Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study.

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9% or BoNT/A administered as a 40 µl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study / Toxina botulínica do tipo-A no tratamento preemptivo da dor trigeminal aguda: estudo pré-clínico duplo cego placebo controlado

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9 percent or BoNT/A administered as a 40 μl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

O objetivo deste estudo foi investigar o efeito preemptivo da neurotoxina botulínica do tipo/A (NTBo/A) através de um modelo de dor orofacial induzida pelo teste da formalina (TF). Rattus norvegicus machos foram injetados no lábio superior com solução salina isotônica 0,9 por cento (SSI) ou NTBo/A (subgrupos 24 horas, 8, 15, 22, 29 ou 36 dias) antes do TF, em dois tratamentos farmacológicos e respectivas avaliações intercalados por 42 dias. Os escores da dor corresponderam ao tempo de fricção da região injetada. Após o primeiro pré-tratamento com NTBo/A no subgrupo 8 dias os escores da fase inflamatória foram menores do que no grupo SSI (p=0,011). Todas as outras comparações não foram significativas. Nos testes de atividade motora não ocorreram diferenças entre SSI e NTBo/A. A NTBo/A pode ser considerada como tratamento preemptivo das dores orofaciais quando utilizada até oito dias antes do estímulo álgico, não havendo consistência terapêutica após um segundo tratamento.

Prevention and management of trigeminal herpes zoster and postherpetic neuralgia.

Herpes zoster (HZ, also known as shingles) is caused by the reactivation of a dormant varicella zoster virus and can be a source of significant morbidity. Oral manifestations can include vesicular eruptions of the mucosa, osteonecrosis with tooth loss, and postherpetic neuralgia (PHN). This article discusses treatment for trigeminal nerve involvement with herpes zoster, as well as for the painful syndrome PHN.

Activation of interleukin-1beta receptor suppresses the voltage-gated potassium currents in the small-diameter trigeminal ganglion neurons following peripheral inflammation.

The glial cytokine, interleukin-1beta (IL-1beta), potentiates the excitability of nociceptive trigeminal ganglion (TRG) neurons via membrane depolarization following peripheral inflammation. Perforated patch-clamp technique was used this study to show that the mechanism underlying the excitability of small-diameter TRG neurons following inflammation is due to IL-1beta. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad. The TRG neurons innervating the site of inflammation were identified by fluorogold (FG) labeling. The threshold for escape from mechanical stimulation applied to the orofacial area in inflamed rats was significantly lower than observed for control rats. IL-1beta at 1nM suppressed total voltage-gated K(+) currents in most TRG neurons (70%) under voltage-clamp conditions in control and inflamed rats. IL-1beta significantly decreased the total, transient (I(A)) and sustained (I(K)) currents in FG-labeled small-diameter TRG neurons in both groups. The IL-1beta-induced suppression of TRG neuron excitability was abolished by co-administration of ILra, an IL-1beta receptor blocker. The magnitude of inhibition of I(A) and I(K) currents by IL-1beta was significantly greater in inflamed rats than in controls. IL-1beta inhibited I(A) to a significantly greater extent than I(K). These results suggest that the inhibitory effect of I(A) and I(K) currents by IL-1beta in small-diameter TRG neurons potentiates neuronal excitability thereby contributing to trigeminal inflammatory hyperalgesia. These findings provide evidence for the development of voltage-gated K(+) channel openers and IL-1beta antagonists as therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.

Percutaneous balloon compression for the treatment of recurrent trigeminal neuralgia: long-term outcome in 29 patients.

OBJECTIVE: To analyze the long-term clinical outcomes and complication rates associated with percutaneous balloon compression (PBC) of the trigeminal ganglion in patients with recurrent trigeminal neuralgia (TN) who were treated surgically with procedures other than PBC. METHODS: In this retrospective study, the authors reviewed the results of 29 patients who underwent 41 PBC procedures for recurrent TN between 1998 and 2006. RESULTS: The overall mean length of follow-up was 49 months (range 1-101). Pain relief was immediate in 24 (83%) patients. There was no pain relief in 5 patients (17%). 2 patients were lost to follow-up. 12 (54.5%) of 22 patients remained pain-free during a mean follow-up period of 65 months (range 40-101). The other 10 patients (45.5%) who had immediate pain relief experienced recurrent pain, with a mean time to recurrence of 7.3 months (17 days to 38 months). PBC was repeated in 11 patients, and was performed a third time in 2 patients. Morbidities included minor dysesthesia (2 patients), masseter weakness (2 patients), corneal anesthesia (1 patient), anesthesia dolorosa (1 patient), and subarachnoid hemorrhage (1 patient with history of multiple myeloma). CONCLUSION: PBC is a useful treatment for patients with recurrent TN who have already been treated surgically. Long-term relief of pain in this subset of TN patients is achieved nearly half of the time with side-effect profiles similar to those reported in published data.

Repeat gamma knife radiosurgery for recurrent or refractory trigeminal neuralgia.

BACKGROUND: Repeat gamma knife radiosurgery (GKRS) is considered to be an effective treatment for refractory or recurrent trigeminal neuralgia (TN). AIMS: The purpose of this report was to demonstrate the relationship between the outcome of repeat GKRS and prior operative procedures on patients with recurrent or refractory TN. MATERIALS AND METHODS: A retrospective analysis was performed on 34 patients with refractory or recurrent TN who had undergone repeat GKRS; 21 patients had undergone other types of procedures, 11 of whom had undergone more than three such procedures prior to radiosurgery. The maximum dose of the repeat procedure was between 60 and 75 Gy. The mean follow-up time was 21.6 months. STATISTICAL ANALYSIS USED: The log-rank test and Fisher's exact test were used to analyze the data. RESULTS: Excellent pain relief was achieved in 14 patients (41.2%) after repeat GKRS, while a successful outcome occurred in 29 of 34 patients (85.3%). Better pain relief occurred in the patients who did not have a prior procedure or who had undergone fewer than three prior procedures (P=0.042). Twenty-four of 25 patients (96.0%) who had recurrent pain had a successful operation and five of nine patients (55.6%) who did not have significant relief of pain after the first procedure had a successful operation. The difference was statistically significant (P<0.01). Only four patients had mild complications. CONCLUSION: It is more likely to relieve pain in patients with recurrent or refractory TN who did not have a prior procedure or who had fewer than three procedures before undergoing their first GKRS. Moreover, it seems that patients who had a good response following the initial GKRS had better results after a repeat procedure.

Gamma Knife surgery for trigeminal pain caused by benign brain tumors.

OBJECT: The authors report the effects of Gamma Knife surgery (GKS) on benign tumor-related trigeminal pain in patients who underwent follow-up for a mean 57.8 months. METHODS: From 1999 to 2004, 21 patients with benign tumor-related trigeminal pain (12 meningiomas and 9 schwannomas) underwent GKS as a primary or repeated treatment. These patients harbored tumors within the radiosurgical target area. For meningiomas, the mean radiosurgical treatment volume was 8.2 ml (range 1.1-21 ml), and the mean radiosurgical tumor margin dose was 12.7 Gy (range 12-15 Gy); for schwannomas, the mean volume was 5.6 ml (range 2-9.2 ml), and the mean marginal dose was 13 Gy (range 11.5-16 Gy). Seven patients underwent retreatment for recurrent or persistent pain; the ipsilateral trigeminal nerve or ganglion was identified and a mean maximal dose of 60.7 Gy (range 40-70 Gy) was delivered to these targets. In 1 patient undergoing retreatment, the margin dose was 12 Gy. The mean age at the time of radiosurgery was 54.5 years (range 18-79 years). RESULTS: The mean follow-up period was 57.8 months (range 36-94 months). Overall, 12 (57%) of 21 patients experienced pain relief without medication after the first GKS and the mean time to drug discontinuation was 10.5 months (range 2-24 months). Initial pain improvement was noted in 17 patients (81%) with a mean time of 3.7 months (range 1 week-10 months) after GKS. Eight patients underwent repeated GKS for persistent and recurrent pain. Four patients (50%) had complete pain relief. The final results of the first and repeated GKS were excellent in 16 patients (76%), and in only 1 patient did GKS fail, and this patient later underwent open surgery. For all 21 patients (100%), control of tumor growth was documented at a mean of 46 months after GKS. Three of 6 patients with pre-GKS facial numbness reported improvement, but 4 suffered new facial numbness after repeated GKS. CONCLUSIONS: Gamma Knife surgery appears to be an effective tool to treat benign tumor-related trigeminal pain and control tumor growth. Repeated GKS targeting the trigeminal root or ganglion can be considered a tool to enhance the efficacy of pain management if pain persists or recurs, but the optimum treatment dose needs further investigation.

Individualized homeopathic treatment of trigeminal neuralgia: an observational study.

OBJECTIVE: To evaluate individualized classical homeopathy in the treatment of idiopathic trigeminal neuralgia (ITN) METHOD: 15 patients with physician-confirmed trigeminal neuralgia were treated with homeopathy. Patients received individualized homeopathic medicines as oral liquid 30C once per month and were followed-up at the end of first, second, third and fourth month. Visual analogue scale (VAS) was used for the evaluation of pain intensity and descriptive criteria were used for evaluation of attack frequency. RESULT: All 15 patients completed treatment. The results for both the reduction of pain intensity and attack frequency were statistically significant (P<0.001) during the four-month evaluation. We observed overall reductions of more than 60% in pain intensity using homeopathic treatment. CONCLUSION: The results suggest that homeopathic treatment is an effective and safe method in the treatment of ITN.

Management of neuropathic orofacial pain.

Current management of painful trigeminal neuropathies relies on pharmacological (topical and systemic), surgical, and complementary modalities. There is, however, a lack of quality research relating to the effectiveness of these modalities. In this review we analyze the available data that relates to the therapy of trigeminal neuralgia, postherpetic neuralgia, and posttraumatic neuropathies and provide clinical guidelines. The review focuses on medical management, as well as surgical and other interventions for painful neuropathies.

Coexistence of TACS and trigeminal neuralgia: pathophysiological conjectures.

BACKGROUND: Trigeminal autonomic cephalgias (TACs) and trigeminal neuralgia are short-lasting unilateral primary headaches whose study is providing insights into craniofacial pain mechanisms. We report on 2 patients in whom trigeminal neuralgia coexists with the TACs paroxysmal hemicrania and SUNCT. CONCLUSION: Coexistence of trigeminal neuralgia with various TAC forms suggests a pathophysiological relationship between these short-lasting unilateral headaches.