<b>OBJECTIVE: </b>In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems.<b>RESEARCH DESIGN AND METHODS: </b>A double-blind, placebo controlled, crossover study of nabilone single doses of 0.5 and 1 mg was conducted. Excitatory systems were elicited using a temporal summation test (tonic heat pain evoked by a Peltier thermode) administered before and after activation of descending inhibitory control (triggered using a counter-irritation procedure). These tests were given before and after drug treatment. Primary outcome measures included average heat pain, temporal summation of heat pain, and drug-induced changes in the strength of descending analgesia. Possible adverse reactions were monitored throughout treatment. Seven men (mean age = 22.5 years, SD = +/- 1.5) and 10 women (mean age = 23.2 years, SD = +/- 2.8) completed this study.<b>RESULTS: </b>Nabilone (1 mg and 0.5 mg) did not reduce the global pain intensity experienced during tonic heat pain (all values of p > 0.18). It also failed to potentiate the strength of descending inhibitory responses (all values of p > 43). Nevertheless, at the highest dose (1 mg), and only for women, nabilone significantly (p = 0.003) dampened the temporal summation experienced during the last portion of the tonic heat pulse test (i.e., the period of time during which temporal summation is greatest). This antihyperalgesic effect was not observed for men (at either 0.5 mg or 1 mg dose), suggesting that the antihyperalgesic properties of cannabinoids are greater for women than for men. Adverse reactions encountered were generally mild and did not provoke the cessation of testing.<b>CONCLUSIONS: </b>Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.
STUDY DESIGN: Case report.
OBJECTIVE: Metastatic epidural spinal cord compression frequently leads to central neuropathic pain symptoms, which are often difficult to treat. A new treatment option is being presented.
SETTING: Antwerp University Hospital, Belgium.
CLINICAL PRESENTATION: We present the case of a 54-year-old male patient suffering from metastatic pancreatic cancer. During the course of his disease the patient developed a paraplegic syndrome due to metastatic compression of the spinal cord. After surgical decompression was performed, patient developed a severe at-level neuropathic pain syndrome, consisting of dysesthesias and allodynia. After all other pharmacological approaches had failed, treatment with lidocaine 5% patches was initiated. Within 4 h after the first patch application, neuropathic symptoms started to disappear. After 12 h, patient had become completely pain free. This topical treatment was continued during several weeks with lasting analgesic efficacy.
CONCLUSION: This case report indicates that transdermal administration of lidocaine could be potentially useful in the treatment of acute central painful neuropathies. We hypothesize that the transdermal administration of lidocaine induces suppression of ectopic impulses in sensitized cutaneous afferents, leading to some kind of 'dewinding syndrome' in the dorsal horn, which in turn leads to a decrease of painful symptoms.
The effects of supratherapeutic dosages of duloxetine, a serotonin and norepinephrine reuptake inhibitor, on blood pressure and pulse rate were assessed in a multicenter, double-blind, randomized, placebo-controlled, crossover study in 117 healthy women aged 19 to 74 years. Dosages were escalated from 60 mg twice daily (BID) to 200 mg BID over 16 days. Vital signs were monitored at baseline, before morning dosing, and sequentially at steady state. Duloxetine produced increases in supine systolic and diastolic blood pressures, which reached maximums of approximately 12 mm Hg and approximately 7 mm Hg above baseline, respectively, during dosing at 120 mg BID and then stabilized. Supine pulse rate increased gradually with dose, reaching 10 to 12 bpm above baseline after 4 days of dosing at 200 mg BID. Duloxetine caused changes in orthostatic blood pressures and pulse rate that reached plateau values after 3 to 4 days of dosing at 160 mg BID and were generally not associated with subjectively reported orthostatic-related adverse events. All vital signs normalized by 1 to 2 days after study drug discontinuation. Prehypertensive subjects may become hypertensive upon initial duloxetine dosing, but this can be predicted from predose blood pressure. Short-term supratherapeutic duloxetine dosages up to 200 mg BID are not well tolerated but are generally not associated with severe, clinically important adverse events. Overall, the types of adverse events reported in this study were similar to those in other studies of duloxetine in healthy subjects.
ZIEL: Wir untersuchten die Wirksamkeit und Verträglichkeit von Paroxetin kontrollierten Freisetzung, Wiederaufnahme ein selektiver Serotonin-Hemmer bei Fibromyalgie.
Methodik: Nach Ausschluss von Patienten mit aktuellen depressiven und Angststörungen, 116 Patienten mit Fibromyalgie wurden in einer 12-wöchigen eingeschrieben, randomisierte, doppel-blinde, Placebo-kontrollierte, Versuch von Paroxetin kontrollierte Freisetzung (12,5-62,5 mg / Tag). Der primäre Endpunkt war Anteil der Responder wie ein> oder = 25% ige Reduktion der Werte auf der Fibromyalgie Auswirkungen Questionnaire (FIQ) von der Randomisierung bis zur Behandlung zu beenden definiert. Die sekundären Endpunkte umfassten Veränderungen in FIQ Partituren, Clinical Global Impression-Improvement (CGI-I) and Severity (CGI-S) Partituren, Visual Analogue Scale für Schmerz-Scores, die Anzahl der tender points, und Werte auf der Sheehan Disability Scale (SDS) .
ERGEBNISSE: Signifikant mehr Patienten in Paroxetin kontrollierte Freisetzung Gruppe (57%) zeigten eine> oder = 25% Ermäßigung in FIQ im Vergleich zu Placebo (33%) (P = 0,016). Paroxetine kontrollierte Freisetzung war signifikant besser als Placebo bei der Verringerung der FIQ Gesamtscore (p = .015). Die CGI-I Bewertungen deutlich favorisiert das Medikament im Vergleich zu Placebo (P <.005). Die Verbesserungen auf anderen sekundären Endpunkte zwischen den 2 Gruppen waren statistisch nicht signifikant. Schläfrigkeit, Mundtrockenheit, verschwommenes Sehen, genitale Störungen und Angst wurden häufiger mit Paroxetin kontrollierte Freisetzung gemeldet. Die mittlere Dosis von Paroxetin kontrollierte Freisetzung betrug 39,1 mg / Tag.
FAZIT: Paroxetine kontrollierte Freisetzung zu sein scheint gut verträglich und verbessert die allgemeine Symptomatik bei Patienten mit Fibromyalgie, ohne aktuelle Stimmung und Angststörungen. Jedoch scheint seine Wirkung auf Schmerzen Maßnahmen als weniger robust.
ZIEL: Die Wirksamkeit und Unbedenklichkeit von Tramadol / Paracetamol (APAP) für das Management von schmerzhafter diabetischer peripherer Neuropathie (DPN) zu untersuchen.
METHODEN: Erwachsene mit schmerzhaften DPN unter Beteiligung der unteren Extremitäten erhielt 37,5 mg tramadol/325 mg APAP oder Placebo, bis zu 1-2 Tabletten viermal täglich für 66 Tage. Befragten bewertet durchschnittlichen täglichen Schmerzen und Schlafstörungen von 0 ("keine") bis 10 ("Schmerz so schlimm, wie man sich vorstellen kann" oder "vollständige Einmischung") jede Nacht. Baseline-Werte wurden für 7 Tage vor Beginn der Studienmedikation aufgezeichnet. Der primäre Endpunkt war die Veränderung der Mittelwert der durchschnittlichen täglichen Schmerz-Scores vom Ausgangswert bis zur letzten Woche. Sekundäre Endpunkte waren die Wirksamkeit Schmerzintensität, Schlafstörungen, Lebensqualität, Stimmung und globalen Eindruck des Wandels. Mögliche Einschränkungen Studie eingeschlossen Genehmigung zur Verwendung von Serotonin-Wiederaufnahme-Hemmern (außer Venlafaxin oder Duloxetin) und das Fehlen einer Tramadol-alone oder APAP-alone-Kontrollgruppe.
ERGEBNISSE: Insgesamt wurden 160 Probanden erhielten Tramadol / APAP und 153 erhielten Placebo. Tramadol / APAP reduziert durchschnittliche tägliche Schmerzintensität im Vergleich zu Placebo signifikant vom Ausgangswert bis zur letzten Woche (-2,71 vs -1,83, p = 0,001). Tramadol / APAP wurde mit signifikant größere Verbesserung als bei Placebo (p <oder = 0,05) für alle Maßnahmen der Schmerzintensität, Schlaf-Störungen, und Gesamteindruck, sowie eine Reihe von Maßnahmen der Verbesserung der Lebensqualität und Stimmung verbunden. Die einzige Nebenwirkung, von> 10% der Probanden entweder in der Tramadol / APAP oder Placebo-Gruppe berichtet, war Übelkeit (11,9% bzw. 3,3% jeweils). Unerwünschte Ereignisse führten zu frühen Studie zum Absetzen von 8,1% und 6,5% der Probanden in den Tramadol / APAP-und Placebo-Gruppe.
FAZIT: Tramadol / APAP war wirksamer als Placebo und war gut in der Behandlung von Schmerzzuständen DPN toleriert.
BACKGROUND: An oromucosal spray has been developed from the major components of marijuana (cannabis), including tetrahydrocannabinol (THC) and cannabidiol (CBD), in alcohol with a peppermint flavouring, designed to be administered as a spray under the tongue or on the buccal mucosa to relieve pain in multiple sclerosis. Although the available evidence indicates its efficacy in this respect, some patients develop oral burning sensation, stinging or white lesions, probably burns.
OBJECTIVE: To investigate the oral side-effects of oromucosal cannabis spray in multiple sclerosis (MS) patients.
DESIGN: A small open observational study.
SUBJECTS AND METHODS: A series of nine patients with MS who had been using a marijuana oromucosal spray for at least four weeks, were asked to attend for oral examination. Patients were asked whether they had ever experienced symptoms (dryness; bad taste; stinging) associated with use of the spray. A standard oral examination was carried out using a dental light, and the presence of any mucosal lesions recorded. Where mucosal lesions were present, patients were advised to discontinue the spray and re-attend after four weeks for re-examination. For ethical reasons, biopsies were not undertaken at the first visit.
RESULTS: Of nine patients invited to participate, eight attended. All admitted to a stinging sensation on using the oromucosal cannabis spray, and four had visible oral mucosal white lesions in the floor of the mouth.
CONCLUSIONS: Although the white lesions observed were almost certainly burns, resolving or improving on discontinuation of use of the medication, the high alcohol concentration of the oromucosal cannabis spray raises concern in relation to chronic oral use.
Chronic noncancer pain includes a heterogeneous group of disorders and is often refractory to treatment. Cannabis products have historically been used for chronic pain and are attracting renewed pharmaceutical interest. Nabilone is a synthetic cannabinoid licensed in Canada for the treatment of severe nausea and vomiting associated with cancer chemotherapy. We have used nabilone off-label for the treatment of chronic noncancer pain since 1999. In this article, we review our clinical experience of 20 adult patients with chronic noncancer pain who had been treated with nabilone and followed up for an average of 1.5 years. Prior to nabilone therapy, patients had used a wide range of therapies, including 11 who had used cannabis. Fifteen patients reported subjective overall improvement with nabilone, and nine reported reduced pain intensity. Beneficial effects on sleep and nausea were the main reasons for continuing use. Intolerable side effects were experienced in three patients (palpitations, urinary retention, dry mouth). Nabilone may be a useful addition to pain management and should be further evaluated in randomized controlled trials.
BACKGROUND: Neuropathic pain (NeP) is a chronic condition that occurs frequently with diabetes and herpes zoster infection. In addition to potentially lasting many years, the relationship between chronic pain, anxiety/depression, and sleep, also referred to as the triad of pain, causes functional impairment in many areas of life.
OBJECTIVE: The aim of this study was to examine the 12-week cost-effectiveness of 2 treatments of NeP, pregabalin versus gabapentin, in managing diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) in a Canadian setting.
METHODS: A stochastic simulation model evaluating NeP treatment was adapted to the Canadian setting. Using data from clinical trials of pregabalin (150-600 mg/d) and gabapentin (900-3600 mg/d), the model simulated 12-week treatment outcomes for patients with DPN or PHN. Resource utilization was identified through an Internet-based survey among 80 Canadian physicians. Utility values (as measured using the EuroQol EQ-5D) were obtained from 126 NeP patients participating in a cross-sectional study conducted at Canadian primary care sites. The economic analysis was expressed as incremental cost per quality-adjusted life year (QALY) gained and as incremental cost per day with no or mild pain. Model sensitivity to changes in key parameters was assessed.
RESULTS: Following 12-week treatment, compared with gabapentin, pregabalin was projected to result in 6 and 9 additional days with no or mild pain for patients with DPN and PHN, respectively. Pregabalin therapy was estimated to provide an additional 0.0047 QALY and 0.0086 QALY over gabapentin administration, for DPN and PHN, respectively. Mean (SE) direct costs per DPN patient were estimated as 837.53 Can dollars (37.31 dollars) (2004 dollars) with gabapentin and 818.49 dollars (36.50 dollars) with pregabalin, and per PHN patient as 720.61 dollars (33.70 dollars) with gabapentin and 667.07 dollars (25.33 dollars) with pregabalin. Model findings were sensitive to variation in the dose and corresponding cost of the comparator, but not in other parameters.
CONCLUSION: Based on the results of this analysis, in the treatment of NeP associated with DPN or PHN, pregabalin was a dominant or cost-effective treatment strategy compared with gabapentin.
ZIEL: Pregabalin bei zentralen neuropathischen Schmerzen mit Verletzungen des Rückenmarks verbunden zu bewerten.
Methodik: Eine 12-wöchige, multizentrische Studie mit Patienten randomisiert entweder mit flexibler Dosierung Pregabalin 150 bis 600 mg / Tag (n = 70) oder Placebo (n = 67), verabreicht bid. Die Patienten durften sich auf die bestehenden, stabilen Schmerztherapie bleiben. Der primäre Wirksamkeits-Endpunkt war die variable mittlere Schmerz-Score, aus Patientensicht letzten 7 Tage täglich Schmerzen Tagebucheinträge abgeleitet. Key sekundären Endpunkten gehörten die Schmerzen Responderraten, die SF-MPQ, Schlafstörungen, Stimmungsschwankungen, und der Patient globales Maß der Veränderung.
Ergebnisse: Der durchschnittliche Ausgangswert des Schmerz-Score war 6,54 in der Pregabalin-Gruppe und 6,73 in der Placebo-Gruppe. Die mittlere Endpunkt Schmerz-Score war in der unteren Pregabalin-Gruppe (4,62) als die Placebogruppe (6,27; p <0,001), mit Wirksamkeit beobachtet bereits in Woche 1 und erhalten für die Dauer der Studie. Die durchschnittliche Pregabalin-Dosis nach der 3-wöchigen Phase der Stabilisierung betrug 460 mg / Tag. Pregabalin war signifikant besser als Placebo bei Endpoint-Bewertungen, die auf SF-MPQ. Die> oder = 30% und> oder = 50% Schmerzen Responderraten waren höher mit Pregabalin als Placebo (p <0,05). Pregabalin mit Verbesserungen bei Schlafstörungen (p <0,001) und Angst assoziiert war (p <0,05) und mehr Patienten berichteten über globale Verbesserung am Endpunkt in der Pregabalin-Gruppe (p <0,001). Leichte oder mittelschwere, waren in der Regel vorübergehend, Schläfrigkeit und Schwindel zu den häufigsten unerwünschten Ereignissen.
FAZIT: Pregabalin 150 bis 600 mg / Tag war wirksam bei der Linderung zentralen neuropathischen Schmerzen, die Verbesserung der Schlaf, Angst, und die allgemeine Zustand des Patienten bei Patienten mit Rückenmarksverletzungen.
Das Ziel dieser Studie war es, die Wirksamkeit und Sicherheit von Duloxetin, ein ausgewogener und potenten Dual-Wiederaufnahme-Hemmer von Serotonin und Noradrenalin, in der Verwaltung der peripheren diabetischen neuropathischen Schmerzen untersuchen. Serotonin und Noradrenalin werden gedacht, um Schmerz über absteigend Schmerzbahnen hemmen. In einer 12-wöchigen, multizentrischen, doppelblinden Studie, erleben 457 Patienten Schmerzen durch Polyneuropathie durch Typ 1 oder Typ 2 Diabetes mellitus randomisiert einer Behandlung mit Duloxetin 20 mg / d (20 mg QD), 60 mg / d zugewiesen wurden verursacht (60 mg QD), 120 mg / d (60 mg zweimal täglich) oder Placebo. Die Diagnose wurde von einem Ergebnis von mindestens 3 auf der Michigan Neuropathie Screening-Instrument bestätigt. Der primäre Wirksamkeits-Maßnahme war der wöchentliche Durchschnittswert der 24-h-Mittelwert Schmerz-Score, der auf einer 11-Punkte (0-10) Likert-Skala (kein Schmerz bis stärkster möglicher Schmerz) bewertet wurde und berechnet aus Tagebuch Noten zwischen zwei Besuche vor Ort . Duloxetin 60 und 120 mg / d zeigte eine statistisch signifikante stärkere Verbesserung im Vergleich zu Placebo auf der 24-h-Mittelwert Schmerz-Score, beginnend 1 Woche nach der Randomisierung und weiter durch den 12-wöchigen Studie. Duloxetin auch von Placebo auf fast allen sekundäre Maßnahmen einschließlich gesundheitsbezogener Maßnahmen Ergebnis getrennt. Signifikant mehr Patienten in allen drei aktiven Behandlungsgruppen erreicht eine 50% ige Reduktion der 24-h-Mittelwert Schmerz-Score im Vergleich zu Placebo. Duloxetin Behandlung galt als sicher und gut mit weniger als 20 Prozent Abbruchrate aufgrund von Nebenwirkungen. Duloxetin bei 60 und 120 mg / d war sicher und wirksam bei der Behandlung von Schmerzen bei diabetischer Polyneuropathie.
In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems.
RESEARCH DESIGN AND METHODS:
A double-blind, placebo controlled, crossover study of nabilone single doses of 0.5 and 1 mg was conducted. Excitatory systems were elicited using a temporal summation test (tonic heat pain evoked by a Peltier thermode) administered before and after activation of descending inhibitory control (triggered using a counter-irritation procedure). These tests were given before and after drug treatment. Primary outcome measures included average heat pain, temporal summation of heat pain, and drug-induced changes in the strength of descending analgesia. Possible adverse reactions were monitored throughout treatment. Seven men (mean age = 22.5 years, SD = +/- 1.5) and 10 women (mean age = 23.2 years, SD = +/- 2.8) completed this study.
RESULTS:
Nabilone (1 mg and 0.5 mg) did not reduce the global pain intensity experienced during tonic heat pain (all values of p > 0.18). It also failed to potentiate the strength of descending inhibitory responses (all values of p > 43). Nevertheless, at the highest dose (1 mg), and only for women, nabilone significantly (p = 0.003) dampened the temporal summation experienced during the last portion of the tonic heat pulse test (i.e., the period of time during which temporal summation is greatest). This antihyperalgesic effect was not observed for men (at either 0.5 mg or 1 mg dose), suggesting that the antihyperalgesic properties of cannabinoids are greater for women than for men. Adverse reactions encountered were generally mild and did not provoke the cessation of testing.
CONCLUSIONS:
Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.
