Does SPM 927 have an analgesic effect in human neuropathic pain? An open label study.

The aim of the study is to establish if the putative anticonvulsant SPM 927 has an analgesic effect in human neuropathic pain and to assess its tolerability. This is an open label study of 25 adult human subjects with resistant neuropathic pain. Subjects were treated with SPM 927 in a dose-escalating scheme to 600 mg daily, if tolerated. Treatment was continued for 4 weeks then withdrawn without tapering. Pain scores were recorded using a 11-point Likert score and a categorical pain-rating scale. Laboratory parameters and, electrocardiographs (ECGs) were collected; side effects were noted. Of the 25 enrolled subjects, 12 completed the study according to the protocol. The remaining subjects dropped out due to adverse events (n=12) or withdrawn consent. Mean daily pain scores (Likert score) fell by 0.83 (95% CI -1.77, +0.11) at the end of maintenance and rose by 0.58 (95% CI -0.23, +1.40) after withdrawal of SPM 927. Similar changes were seen in the categorical pain-rating scores. There were decreases in the mean scores for shooting pain, paraesthesia, and allodynia, but much less change in the numbness and burning-pain scores. The most common side effects were nausea, dizziness, leukocytosis, and increased ALT. No consistent changes in ECG recordings or haemodynamic variables were observed. SPM 927 may have an analgesic effect in human neuropathic pain and was reasonably well tolerated in this study. These data support the continued clinical development of SPM 927 for neuropathic pain.

The addition of glyceryltrinitrate to capsaicin cream reduces the thermal allodynia associated with the application of capsaicin alone in humans.

The aim of this study was to determine whether topical application of capsaicin cream causes thermal allodynia and the extent to which this is attenuated by the addition of glyceryltrinitrate (GTN). This was a double blind placebo controlled study of 40 consenting adult subjects. Each of four cream combinations (GTN, capsaicin, GTN/capsaicin and vehicle) were applied to the subjects with at least a 1 day interval between each application. Water at a known temperature was applied to the standard area of skin where cream had been applied. Subjects rated the resulting thermal allodynia using a 0-10 Likhert score. Thermal allodynia is usually apparent when warm water is applied to skin containing capsaicin. The thermal allodynia caused by the topical application of capsaicin was significantly reduced by the addition of GTN. The addition of GTN to capsaicin cream significantly reduces the thermal allodynia associated with the application of capsaicin cream alone.

The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study.

The aim of this study was to assess if the pain of osteoarthritis is reduced by topical capsaicin and to determine whether addition of glyceryl trinitrate has an effect on analgesic efficacy and tolerability of capsaicin. A randomized, double blind, placebo controlled study was carried out on 200 adult patients attending a Pain Clinic with osteoarthritis pain. Patients applied one of four creams topically over the affected joint over a 6 week period. Creams contained either placebo (vehicle), 0.025% capsaicin, 1.33% glyceryl trinitrate or 0.025% capsaicin + 1.33% glyceryl trinitrate. Analgesic efficacy, tolerability of cream and analgesic consumption were assessed. One hundred and sixty-seven of 200 patients completed the study. Baseline visual analogue scores (0-10 scale) for pain were 6.40. There was a significant reduction in pain scores in the glyceryl trinitrate group (mean decrease 0.59, p< 0.05, 95% confidence limits 0.04-1.14), 0.025% capsaicin group (mean decrease 0.5, p< 0.05, 95% confidence limits 0.05-1.05) and the glyceryl trinitrate capsaicin group (mean decrease 1.1, p<0.05, 95% confidence limits 0.22-1.98). Baseline discomfort of application scores were similar for all but the capsaicin groups (they were significantly higher (by 2.1 units, p< 0.001)). The odds ratio in favour of continuing treatment was 2.1 (95% confidence limits 1.0-4.4) for glyceryl trinitrate and 2.4 (95% confidence limits 1.2-5.1) for capsaicin and 5.0 (95% confidence limits 3.8-6.4) for capsaicin GTN combination. The study showed that topical capsaicin and glyceryl trinitrate have an analgesic effect in painful osteoarthritis. When used together this effect is increased with the combination being more tolerable than capsaicin alone. Analgesic consumption is decreased by capsaicin, glyceryl trinitrate and to a greater extent by both combined.

Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.

AIMS: To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3. 3% doxepin and 0.025% capsaicin in human chronic neuropathic pain. METHODS: A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0-10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded. RESULTS: Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin. CONCLUSIONS: Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0. 025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia.

Lamotrigine in the management of neuropathic pain: a review of the literature.

OBJECTIVE: The purpose of this review is to examine the accumulating evidence indicating that lamotrigine is effective in the treatment of neuropathic pain. METHOD: A review of the available literature. RESULTS: Neuropathic pain is a debilitating series of conditions that are often poorly controlled. The molecular action of lamotrigine in terms of its effects in preclinical models of pain and hyperalgesia are considered along with the accumulating evidence suggesting that lamotrigine may be effective in the clinical management of neuropathic pain. CONCLUSION: A review of the literature suggests that lamotrigine may be effective in the management of neuropathic pain.

To determine whether the temperature of 2% lignocaine gel affects the initial discomfort which may be associated with its instillation into the male urethra.

OBJECTIVE: To determine whether the temperature of 2% lignocaine hydrochloride gel affects the initial discomfort during instillation into the male urethra. PATIENTS AND METHODS: Sixty consenting men were randomized to receive 11 mL of 2% lignocaine hydrochloride gel (Instillagel, Farco-Pharma GmbH, Cologne, Germany) at 4 degrees C, 22 degrees C or 40 degrees C. The three groups were well matched for age and numbers of previous flexible cystoscopies. The gel was instilled by one operator and the patients were then immediately asked to score the pain on instillation using a 100-mm nongraphical visual analogue scale. RESULTS: Compared with the control group (at 22 degrees C), there was a statistically significant reduction in pain score in the group receiving cold gel (Student's t-test, P<0.05). CONCLUSION: The cooling of 2% lignocaine gel significantly reduced the initial discomfort associated with its delivery into the male urethra before any form of urethral instrumentation.

200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial.

Anticonvulsant drugs are commonly used in neuropathic pain. There is anecdotal evidence of an analgesic effect of the anticonvulsant lamotrigine in neuropathic pain, but this is verified by few randomised controlled trials. This randomised, double-blind, placebo controlled trial of examined the effect of lamotrigine in a dose increasing to 200 mg in 100 patients with neuropathic pain. Eight patients failed to attend for review, 18 withdrew early and 74 provided results. There was no statistical difference in age, sex or duration pre-treatment pain in the two groups. Total pain, the character of the pain, sensitivity, numbness, paraesthesia, sleep, mobility, mood, quality of life and analgesic consumption were measured. There was a correlation between burning and numbness (P<0. 01), shooting pain and total pain (P<0.01) and between analgesic consumption and mobility (P<0.05) throughout the study period. There were no correlation between any other measured variable. There was no significant change in any variable measured over the eight week period when lamotrigine was used. It is concluded that at the dose used and using the dose escalation regime described, lamotrigine had no effect on either pain, component pain symptoms or quality of life variables.

Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study.

UNLABELLED: Neuropathic pain responds inconsistently to opioids and nonsteroidal antiinflammatory drugs. However, oral anticonvulsants have a proven analgesic effect on neuropathic pain, but may not be practical in an acute flare-up. Phenytoin was the first oral anticonvulsant used as an analgesic for neuropathic pain. There have been few studies on the parenteral analgesic effect of this drug. In this randomized, double-blind, placebo-controlled, crossover study of 20 patients with acute flare-ups of neuropathic pain, we compared a 2-h placebo infusion with a 2-h infusion of 15 mg/kg phenytoin. Overall pain, shooting pain, burning pain, paresthesia, numbness, and sensitivity were measured using a 10-cm linear visual analog score. Numbness and sensitivity were reduced in the placebo group during infusion, but not in the 7 days after infusion. In the phenytoin group, there were significant reductions in burning pain (P < 0.05), shooting pain (P < 0.001), sensitivity (P < 0.001), numbness (P < 0.05), and overall pain (P < 0.005) during the infusion period. The reduction in overall pain persisted for 1 day, in sensitivity for 2 days, and in shooting pain for 4 days after infusion. We conclude that IV infusion of 15 mg/kg phenytoin has an analgesic effect in acute flare-ups of neuropathic pain and that this relief outlives both the infusion time and plasma half-life of phenytoin. IMPLICATIONS: Oral phenytoin can relieve neuropathic pain. The aim of this study was to examine the effect of IV phenytoin on neuropathic pain. The results indicate that IV phenytoin may be used to treat flare-ups of chronic neuropathic pain.

The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain.

UNLABELLED: The analgesic efficacy of morphine is sometimes only partial in patients with chronic benign pain. Among the possible factors contributing to this limitation are increased levels of cholecystokinin (CCK). We performed this prospective, placebo-controlled, double-blind, cross-over study to examine the effect of proglumide, a nonspecific CCK agonist, on analgesia in patients taking morphine on a chronic basis. Forty patients with intractable pain who were taking sustained-release morphine were recruited, and we obtained results from 36 of these patients. Median visual analog scale scores before the study were 8 and 7 after the addition of placebo for 2 wk (P = 0.16), and 6 after proglumide for 2 wk (P = 0.002). Mobility was unchanged by proglumide or placebo. Of the 36 patients, 13 elected to continue receiving proglumide after the study. We conclude that proglumide enhances the analgesia produced by morphine in some, but not all, patients with chronic benign pain. IMPLICATIONS: The pain-killing effect of morphine is incomplete in some patients. Increasing doses may be needed to maintain the initial effect. The peptide cholecystokinin may be partially responsible for this. In this study, we demonstrated that the cholecystokinin antagonist proglumide increases the analgesic effect of morphine in some patients with chronic benign pain.

Preoperative application of piroxicam gel compared to a local anaesthetic field block for postoperative analgesia.

The non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis and hence have an analgesic action. Following topical administration, the drug is concentrated in the tissues and so can have a local analgesic effect. This study investigated the effect of the preoperative application of topical piroxicam on postoperative analgesic requirement compared to a placebo group and a conventional local anaesthetic field block. Forty-two patients presenting for in-patient inguinal hernia repair were randomly allocated on a double-blind basis to have either piroxicam gel 15gm applied preoperatively, or an inguinal field block with 20 ml of 0.375% bupivacaine following induction of anaesthesia, or no treatment. Postoperative Visual Analogue Scores for pain on moving in group P, I or C on admission at 1h, 2h, and 4 h following surgery were: 2 vs 1 vs 6.5; 3 vs 3 vs 5; 3 v 2 vs 4.5; 3 vs 2 vs 5.0, respectively (P < 0.005). Median(range) time to first analgesia was 25.4(15-70) min in group I, 30.3(10-49) min in group P; this was not significantly different from group C21.5(7-70) min. Over the first 24 hours the postoperative morphine requirement was significantly less in the two treatment groups 30(20)mg in group I and 34(17) mg in group P and 71(15) in group C, P < 0.0001. There were no apparent NSAID-induced side-effects, or effects on wound healing. The preoperative administration of piroxicam (15gm) topically compared favourably with a preoperative local anaesthetic field block with respect to VAS scores, time to first analgesia and total morphine consumption. And both treatment groups provided significantly superior analgesia than the control group.