Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain

This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and tolerability of lamotrigine added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic in patients whose neuropathic pain was inadequately controlled with these medications. Patients with neuropathic pain from diabetic peripheral neuropathy, postherpetic neuralgia, traumatic/surgical nerve injury, incomplete spinal cord injury, trigeminal neuralgia, multiple sclerosis, or HIV-associated peripheral neuropathy, who had a mean weekly pain score > or =4 on an 11-point numerical rating scale, were randomized to receive a flexible dose of lamotrigine 200, 300, or 400mg daily (n=111) or placebo (n=109) for up to 14 weeks (including eight weeks of dose escalation) in addition to their prestudy regimen of gabapentin, a tricyclic antidepressant, or a nonopioid analgesic. No statistically significant difference in the mean change in pain-intensity score from baseline to Week 14 (primary endpoint) was detected between lamotrigine and placebo (P=0.67). Differences between lamotrigine and placebo were not statistically significant for secondary efficacy assessments, including mean changes from baseline in the Short-Form McGill Pain Questionnaire, the Neuropathic Pain Scale, rescue medication use, and the percentages of patients rated as much improved or very much improved at the end of treatment on the Clinician Global Impression of Change scale and the Patient Global Impression of Change scale. Lamotrigine was generally well tolerated. Lamotrigine (up to 400 mg/day) added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic did not demonstrate efficacy as an adjunctive treatment of neuropathic pain but was generally safe and well tolerated.     

经皮半月节后根甘油阻滞治疗三叉神经痛3370例临床研究

目的:分析半月节后根甘油阻滞术(PRGR)治疗三叉神经痛的长期随访结果,评价疗效、复发率及主要并发症面部感觉障碍的恢复预后.方法:1983-2003年完成的PRGR手术3370例,随访3-23年,平均13.1年.结果:短期疼痛完全缓解率99.79%,随访2750例,死于其他疾病112例,失访508例,总复发率35%,1年内复发率0.3%,1～5年21%,5～10年7%,10～15年4%,15～23年3%.并发症主要为面部感觉迟钝,触觉重于痛觉,痛觉先于触觉恢复,除34例(1%)遗留永久性轻度感觉迟钝外,面部感觉半年内恢复.其他并发症包括失明1例,角膜炎6例,因角膜溃疡致失明1例,动脉性出血5例,咀嚼肌无力2例,继发于感染的面部畸形1例,无痛性感觉缺失和死亡病例.结论:半月节后根甘油阻滞治疗三叉神经痛是一种微创的外科治疗手段,操作简单,疼痛缓解快,主要并发症绝大多数呈损害可逆性,复发时限不一,可作为首次外科治疗推荐给药物治疗无效患者.     

Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’ design

Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one-quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2-stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3-period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the ‘enriched enrollment’ second stage (study II), consisting of an additional 4 double-blind, randomized, 1-week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4–35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the -adrenergic blocker phentolamine had relief of pain, suggesting that clonidine's pain relief is not mediated by a decrease in sympathetic outflow. A post-hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials.     

Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study.

Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that might develop after breast surgery. Like many other forms of neuropathic pain, it is relatively resistant to treatment and negatively affects the quality of life. A double-blind, randomized, placebo-controlled pilot trial was conducted to study the analgesic efficacy of perioperative administration of the N-methyl-D-aspatrate (NMDA) receptor antagonist amantadine in preventing PMPS after mastectomy plus axillary lymph node dissection (ALND). In the study group, a regimen of 200 mg/day of amantadine was started 1 day before surgery and continued for 14 days, whereas the control group received a placebo. Patients were required to indicate the exact location of their pain and to record its level at 1, 3, and 6 months after surgery. Neurologic examination and Quantitative Thermal Testing (QTT) were performed 1 and 6 months after surgery. On both the neurologic examination and the QTT, all patients, regardless of the perioperative intervention (amantadine or placebo), presented evidence for nerve injury, manifested primarily by painful hypoesthesia (anesthesia dolorosa) in the axilla or inner arm. PMPS persisted for the entire duration of the study in 82% of the patients who were available for follow-up. The average intensity of the pain was moderate in both groups and tended not to decline over time. No differences between the 2 groups in any of the outcome parameters reached statistical significance. According to the results of the present pilot study, the NMDA antagonist amantadine does not prevent the development of PMPS in patients who undergo breast surgery with ALND. PERSPECTIVE: Breast surgery that involves ALND seems to uniformly cause nerve injury, which cannot be prevented by the perioperative administration of 200 mg of amantadine. It is most commonly presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner arm area, which is moderate in intensity and likely to persist for at least 6 months.     

Tractotomy and partial nucleotomy as a form of therapy in refractory pain of the trigeminal nerve and cancer pain in the head and neck area]

Persistent trigeminal neuralgia, herpes zoster neuralgia of the first division of the trigeminal nerve and pain caused by cancer situated in the head and neck pose frustrating problems for patients and physicians. Tractotomy and/or partial vertical nucleotomy of the subnucleus caudalis nervi trigemini offers a logical approach to the treatment of such pain, since these structures contain fibres of the Vth nerve, as well as the somatosensory fibres of the VIIth, IXth and Xth nerve. Tactile and some thermal sensitivity of the face is preserved and anaesthesia dolorosa and keratitis neuroparalytica is avoided. Over the past 30 years 370 patients with therapy-refractory trigeminal pain, pain due to cancer of the head and neck and herpes zoster trigeminal pain were treated by means of tractotomy (personal series of V. Grunert), including 30 patients who underwent partial vertical nucleotomy. The mean age of the patients was 68 years (range 54-84 years). The mortality in this series was 0.9% (4 patients; one operative mortality due to air embolism, one postoperative cardiac failure following myocardial infarction and two intracerebral haematomas). 60% of the patients with persistent trigeminal neuralgia were pain-free and 28% improved, whereas 12% were unchanged or suffered from recurrent pain. Of the patients with cancer who complained of pain derived from the Vth, VIIth, IXth and Xth nerve, 40% demonstrated marked pain relief and 60% showed no improvement. Tractotomy and partial vertical nucleotomy offer a valuable method in experienced hands for relieving pain where other methods have failed.     

Rationale and design of a randomized double-blind clinical trial in breast cancer: Dextromethorphan in chemotherapy-induced peripheral neuropathy

BackgroundAnti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia.Methods and designThis trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0–10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α = 0.05.DiscussionConsidering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer.     

Percutaneous controlled thermocoagulation in the treatment of trigeminal neuralgia

This study reviews the results and complications of 162 percutaneous thermocoagulations of the gasserian ganglion in 124 patients with typical idiopathic trigeminal neuralgia. The mean duration of follow-up observation was 3.7 years (range, 1-6 years). One hundred eighteen of 124 patients continued to show complete pain relief 1 month after the operation, and at the end of follow-up observation, 83 of 124 patients (67%) continued to enjoy complete pain relief (recurrence rate, 28.2%). Anesthesia dolorosa occurred in 3% of cases, dysesthesia in 3%, and paresthesia in 17%; neuroparalytic keratitis with permanent reduction of visual acuity was observed in 2% of cases, permanent diplopia in 1%, permanent hearing deficit in 3%, and permanent impairment of mastication in 3%. We compare thermocoagulation with other surgical procedures (microvascular decompression, glycerol injection, and percutaneous decompression) used in the treatment of trigeminal neuralgia.     

The use of botulinum toxin for the treatment of chronic facial pain.

An open label pilot study was conducted to evaluate efficacy of botulinum toxin injections for the treatment of patients with chronic facial pain seeking tertiary care at a pain clinic. Diagnoses included temporomandibular joint syndrome, postsurgical pain syndromes, essential headache, and idiopathic trigeminal neuralgia. Thirty-three (75%) of 44 patients favorably responded, including 8 of 11 patients with trigeminal neuralgia. The duration of beneficial effect ranged from 2 to 4 months, and all responding patients desired further injections. Complications were mild and included temporary facial asymmetry and weakness secondary to neuromuscular effects of botulinum toxin. Doses ranged from 25 to 75 LD 50 units with Hall strain-derived botulinum toxin type A. A small degree of facial edema during pain or erythema seemed to have predictive value when categorically evaluated against response.     

Treatment of idiopathic trigeminal neuralgia: comparison of long-term outcome after radiofrequency rhizotomy and microvascular decompression. (Heidelberg College of Medicine, Heidelberg, Germany) Neurosurgery. 2001;48:1261–1267.

The purpose of this study was to evaluate the long‐term outcome of patients after either percutaneous trigeminal rhizotomy or microvascular decompression (MVD) for idiopathic trigeminal neuralgia at a single institution. Overall, the results of the study showed that there was a 50% risk of recurrence of pain 2 years after percutaneous radiofrequency rhizotomy. Conversely, 64% of the patients who underwent MVD remained completely pain free 20 years postoperatively. Patients without sensory impairment after MVD were pain free significantly longer than patients who experienced postoperatively hypesthesia or partial rhizotomy. Conclude that because it is curative and nondestructive, MVD is considered the treatment of choice for trigeminal neuralgia in otherwise healthy people. In this study, it was proved to be a more effective and long‐lasting procedure for patients with typical trigeminal neuralgia than radiofrequency rhizotomy. Patients without postoperative sensory deficit remained pain free significantly longer, which is a strong argument against the “trauma” hypothesis of this procedure. Comment by Ron Pawl, M.D. This paper is noteworthy in that comparing the follow‐up on 225 of 378 patients who underwent microvascular decompression (MVD) with 206 of 316 who underwent radiofrequency thermocoagulation (RFT), the RFT group stood a 50% risk of recurrent pain by 2 years after the procedure, whereas 64% of those undergoing MVD were pain‐free after 20 years. Furthermore, after MVD, those patients with no postoperative sensory deficit, measured with von Frey hairs, remained pain‐free longer than those with a sensory deficit. This latter finding flies in the face of the concept that to be effective, surgery for trigeminal neuralgia must damage the nerve. The whole concept of RF lesioning of the nerve is to damage it enough to deaden the trigger zone of the affected nerve branch. However, in this study it is noted that postoperative hypesthesia was only temporary after RF lesioning, which might well explain the high rate of pain recurrence in this series. Although the long‐term pain relief in the MVD group is excellent, it must be weighed against the complications. In the MVD group, there were 3 mortalities, diminished hearing in 5%, loss of hearing in 2.6%, facial paralysis in 4 patients, and tinnitus in 4 patients, none of which occurred in the RF group.     

Retrogasserian glycerol injection: a retrospective study of 112 patients

From 1984 to 1989, 112 patients with typical drug-refractory trigeminal neuralgia were treated by retrogasserian glycerol injection. The present study assesses results and complications after a mean follow-up period of 3.5 years (range 0.1-5.5 years). One hundred and three of 112 patients (91.9%) showed complete pain relief 1 month postoperatively, and at the end of follow-up 80 patients (71.4%) were still enjoying complete pain relief (recurrence rate 20.5%). Abnormal facial sensations were noted in 49 patients, the most common complication being mild hypoesthesia (32% of patients), while paresthesia occurred in 19% of cases and dysesthesia in 3%. The corneal reflex was absent in 3% of patients and reduced in 5%. None of the patients developed anesthesia dolorosa, permanent masseter weakness, neuroparalytic keratitis, or diplopia.     

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy

Dextromethorphan is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that NMDA-receptor antagonists may potentiate the effect of analgesics such as morphine, local anesthetics and NSAIDs. Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting, possibly related to administration of insufficient doses of the drug. Fifty patients scheduled for non-malignant elective abdominal hysterectomy in general anesthesia were randomized to receive oral dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received patient-controlled analgesia with morphine for 24 h postoperatively as the only analgesic. Patient-controlled analgesia (PCA) morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during cough, or during mobilization, pressure pain detection thresholds, von Frey hair pain detection thresholds, or peak flow. At 24 h after operation, hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption (Rs=0.28, P=0.05). Three months postoperatively, hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (nausea, vomiting, sedation). In conclusion, oral dextromethorphan 150 mg reduced PCA morphine consumption immediately (0-4 h) after hysterectomy, without prolonged effects on pain or wound hyperalgesia. A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption was demonstrated.     

Effectiveness and time to onset of pregabalin in patients with neuropathic pain

BACKGROUND: The data from a previously published 12-week randomised, double-blind, placebo-controlled multicentre study on the efficacy and safety of pregabalin were analyzed for time to onset of analgesic action with neuropathic pain. PATIENTS AND METHODS: A total of 338 patients with postherpetic neuralgia or painful diabetic peripheral neuropathy were treated with flexible or fixed regimens of pregabalin at daily doses of up to 600 mg/day (n=141 and 132, respectively) or placebo (n=65). RESULTS: Under fixed dose treatment, a decrease of one full point on the 11-point numerical rating pain scale was reached on day 1, two full points on day 13, and three full points on day 23 (under flexible dose pregabalin: on days 6, 17 and 30). In both treatment arms, pain reduction was statistically significant (P=0.001, P=0.002 vs placebo, respectively). CONCLUSION: In patients with chronic neuropathic pain, the analgesic effect of both pregabalin treatment regimens was high and associated with a rapid time to onset.     

A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: the aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial.

Topical aspirin/diethyl ether (ADE) mixture was used to treat 45 consecutive patients with acute herpetic neuralgia (AHN) (n = 28) and with post-herpetic neuralgia (PHN) (n = 17) in an open-label study. Good-to-excellent results were achieved by 93% of AHN patients and by 65% of PHN patients. Earlier treatment yielded better results for the AHN but not the PHN group. The topical treatment seemed to accelerate the healing of acute herpetic skin lesions and possibly modulate the severity of the herpetic infection. Furthermore, a striking reduction in the percentage of AHN patients developing PHN was observed in the treated group, as compared with the disease natural history reported in the literature (4 vs. 50-70%). Treatment tolerance was excellent with no adverse effect observed. In addition to the open trial, a pilot double-blind crossover placebo-controlled study (n = 11) compared the analgesic efficacy of ADE with two other NSAID (indomethacin and diclofenac) drug/ether mixtures. Aspirin (but not indomethacin and diclofenac) was significantly superior to placebo as regards pain relief (P less than 0.05).     

Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets

This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.     

Pathophysiology of trigeminal neuralgia: the ignition hypothesis.

There are no satisfactory animal models of trigeminal neuralgia, and it is difficult to obtain essential data from patients. However, trigeminal neuralgia presents with such idiosyncratic signs and symptoms, and responds to so distinctive a set of therapeutic modalities, that scientific deduction can be used to generate likely hypotheses. The ignition hypothesis of trigeminal neuralgia is based on recent advances in the understanding of abnormal electrical behavior in injured sensory neurons, and new histopathologic observations of biopsy specimens from patients with trigeminal neuralgia who are undergoing microvascular decompression surgery. According to the hypothesis, trigeminal neuralgia results from specific abnormalities of trigeminal afferent neurons in the trigeminal root or ganglion. Injury renders axons and axotomized somata hyperexcitable. The hyperexcitable afferents, in turn, give rise to pain paroxysms as a result of synchronized afterdischarge activity. The ignition hypothesis accounts for the major positive and negative signs and symptoms of trigeminal neuralgia, for its pathogenesis, and for the efficacy of treatment modalities. Proof, however, awaits the availability of key experimental data that can only be obtained from patients with trigeminal neuralgia.     

Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders

BACKGROUND: The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is the first drug approved in the United States and in Europe for both conditions. In June 2005, pregabalin was approved as an adjunctive treatment in adults with partial-onset seizures. The FDA currently is considering the approval of pregabalin as adjunctive therapy in adults with generalized anxiety disorder (GAD) or social anxiety disorder (SAD). OBJECTIVES: The goals of this review were to summarize the pharmacology, pharmacokinetics, efficacy, and tolerability of pregabalin; review its approved uses in the management of neuropathic pain and refractory partial-onset seizures; and investigate its potential use in patients with GAD or SAD. METHODS: Relevant English-language literature was identified through a search of MEDLINE (1993-June 2006) and International Pharmaceutical Abstracts (2000-June 2006). The search terms included pregabalin, Lyrica, S-(+)-3 isobutyl-gaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008. RESULTS: In 4 clinical trials in a total of 1068 patients with diabetic peripheral neuropathy, the patients receiving pregabalin 300 to 600 mg/d had significantly greater improvement in mean pain scores than placebo recipients (P < or = 0.01). Patients with postherpetic neuralgia receiving pregabalin 450 to 600 mg/d had significantly greater improvement in relief of pain and pain-related sleep interference than placebo recipients (P < or = 0.002). Patients with refractory partial-onset seizures who received pregabalin 150 to 600 mg/d (divided into 2 or 3 doses) concomitantly with antiepileptic drugs had significantly fewer seizures than placebo recipients (P < or = 0.001). In the 3 studies that evaluated the efficacy of pregabalin in patients with GAD or SAD, the patients receiving pregabalin 200 to 600 mg/d (divided into 2 or 3 daily doses) had a significantly greater reduction in mean pain scores on the Hamilton Anxiety Scale than placebo recipients (P < or = 0.01). Across all the reviewed clinical trials, the most commonly reported adverse effects (AEs) were those affecting the central nervous system, including somnolence (< or =50%), dizziness (< or =49%), and headache (< or =29%). AEs resulted in withdrawal from the study in < or =32% of patients. CONCLUSIONS: Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures. The available data suggest that pregabalin may be beneficial as an adjunctive therapy in adult patients with GAD or SAD.     

Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial.

This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy. PERSPECTIVE: Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.     

Percutaneous balloon compression for trigeminal neuralgias and autonomic cephalalgia

OBJECTIVE: This prospective study aimed to evaluate the results of percutaneous trigeminal ganglion balloon compression (BC) in patients with various types of trigeminal neuralgia (TN) and autonomic cephalalgia. METHODS: Twenty-five consecutive patients underwent BC and were followed up for 27-60 months. They were divided into 2 groups: group A (n=18) patients with idiopathic TN and group B (n=7) patients with secondary TN (n=5) and trigeminal autonomic cephalalgia (TAC) (n=2). RESULTS: Postoperatively, 15 patients in group A experienced pain relief, one required medication and 2 had no response; in group B, 6 were free of pain, including the 2 patients with TAC, and one required medication. Complications in both groups were either functionally trivial or infrequent. None of the patients developed keratitis or anesthesia dolorosa. Pain recurrence occurred early (<6 months) in one patient from group B, and late in 2 patients from group A. CONCLUSION: Balloon compression is a minimally invasive procedure that seems to be comparably successful for idiopathic and secondary TN, as well as TAC. However, further studies are deemed necessary to establish it as the first-line treatment in medically resistant trigeminal pain.     

Efficacy and Safety of Carisbamate in Patients with Diabetic Neuropathy or Postherpetic Neuralgia: Results from 3 Randomized,Double‐Blind Placebo‐Controlled Trials

The results of 3 proof‐of‐concept studies to evaluate carisbamate's efficacy and safety in treating neuropathic pain are presented. In studies 1 (postherpetic neuralgia, n = 91) and 2 (diabetic neuropathy, n = 137), patients received carisbamate 400 mg/day or placebo for 4 weeks and then crossed over to the other treatment for 4 weeks. In study 3 (diabetic neuropathy, higher carisbamate doses), patients (n = 386) were randomized (1:1:1:1) to receive either carisbamate 800 mg/day, 1200 mg/day, pregabalin 300 mg/day or placebo for 15 weeks. Primary efficacy end point was the mean of the last 7 average daily pain scores obtained on days the study drug was taken, for all 3 studies. Least square mean (95% CI) differences between carisbamate and placebo groups on the primary end point were as follows: study 1: ?0.512 (?1.32, 0.29) carisbamate 400 mg/day; study 2: ?0.307 (?0.94, 0.33) carisbamate 400 mg/day; and study 3: ?0.51 (?1.10, 0.08), carisbamate 800 mg/day; ?0.55 (?1.13, 0.04), carisbamate 1200 mg/day; and ?0.43 (?1.01, 0.15), pregabalin 300 mg/day. Neither carisbamate (all 3 studies) nor pregabalin (study 3) significantly differed from placebo, although multiple secondary end points showed significant improvement in efficacy with carisbamate in studies 1 and 2. Dizziness was the only treatment‐emergent adverse event occurring at ≥10% difference in carisbamate groups versus placebo (study 1: 12% vs. 1%; study 3: 14% vs. 4%; study 2: 1% vs. 2%). Carisbamate, although well tolerated, did not demonstrate efficacy in neuropathic pain across these studies, nor did the active comparator pregabalin (study 3).