Magdi Hanna

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients

Background: Neuropathic pain remains one of the most challenging pain syndromes; under‐diagnosed, poorly managed and associated with significant co‐morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose‐related adverse events.

Effects of mood on pain responses and pain tolerance: An experimental study in chronic back pain patients

&NA; Although chronic pain and depression commonly co‐occur, causal relationships have yet to be established. A reciprocal relationship, with depression increasing pain and vice versa, is most frequently suggested, but experimental evidence is needed to validate such a view. The most straightforward approach would be a demonstration that increasing or decreasing depressed mood predictably modifies pain responses. The current experiment tested whether experimentally induced depressed and happy mood have differential effects on pain ratings and tolerance in 55 patients suffering from chronic back pain. Participants were randomly assigned to depressed, neutral (control) or elated mood induction conditions. They completed a physically passive baseline task prior to receiving mood induction, then a clinically relevant physically active task (holding a heavy bag) to elicit pain responses and tolerance. Measures were taken immediately after the baseline task and immediately after the mood induction to assess the changes in mood, pain ratings and tolerance before and after the experimental manipulation. Results indicate that the induction of depressed mood resulted in significantly higher pain ratings at rest and lower pain tolerance, whilst induced happy mood resulted in significantly lower pain ratings at rest and greater pain tolerance. Correlations between changes in mood on the one hand and changes in pain response and pain tolerance on the other hand were consistent with these findings. It is concluded that, in chronic back pain patients, experimentally induced negative mood increases self‐reported pain and decreases tolerance for a pain‐relevant task, with positive mood having the opposite effect.

Ketanserin in reflex sympathetic dystrophy. A double-blind placebo controlled cross-over trial

Ketanserin, a selective S2 serotonergic antagonist, was assessed against placebo in a double-blind cross-over study of 16 patients with chronic peripheral burning pain. Nine of these had signs of reflex sympathetic dystrophy (RSD). All patients underwent 4 intravenous regional treatments, 2 with ketanserin (10 mg for upper limb pain, 20 mg for lower limb pain) and 2 with placebo. In those patients with RSD ketanserin and not placebo provided significant (P less than 0.05) sustained pain relief as assessed by linear analogue scales. In patients who did not fulfil the criteria for RSD no significant relief was seen with placebo or ketanserin. Following tourniquet release, drowsiness, shakiness and faintness were reported at a higher (P less than 0.05) frequency after ketanserin than after placebo. All side effects were mild and transient, and no changes occurred in heart rate or blood pressure following ketanserin that were significantly different from those seen following placebo. A role for serotonin in the pathogenesis of RSD is proposed.

Mental defeat in chronic pain : initial exploration of the concept

Objectives“Mental defeat” has been found to be an important psychologic reaction to painful trauma. Chronic pain patients also report mental defeat in relation to their experience of pain episodes. A measure of mental defeat was devised and evaluated in terms of (1) psychometric properties and (2) specificity of scores in relation to disabling chronic pain. MethodsA total of 304 participants completed the Pain Self Perception Scale, a questionnaire designed to measure mental defeat as a reaction to pain. Participants also completed the Short-Form McGill Pain Questionnaire and Hospital Anxiety and Depression Scale. Chronic pain patients from a tertiary hospital clinic (n=94) were compared with patients experiencing acute pain (n=38), pain-free controls (n=79), community volunteers suffering from chronic pain (n=32) or acute pain (n=30), and patients diagnosed with anxiety disorders (n=31). Test-retest reliability was assessed in subsamples of chronic pain patients and community volunteers. ResultsThe mental defeat measure was both internally consistent and reliable. Chronic pain patients showed elevated levels of mental defeat relative to all other groups, including people with chronic pain of the same intensity of pain who were not seeking treatment. Pain-specific mental defeat may be linked to disability and the seeking of specialist treatment. ConclusionsResearch on mental defeat may allow the development of new treatment strategies for chronic pain syndromes and a better understanding of the link between chronic pain, depression, and posttraumatic stress disorder.

An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS ® hydromorphone in patients with chronic cancer pain

BackgroundOpioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS® hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS® hydromorphone in patients with chronic cancer pain.MethodsIn this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS® hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS® hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS® hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.ResultsThe mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS® hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).ConclusionThe results of this extension study suggest that long-term repeated dosing with once-daily OROS® hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.

Thalamic pain--the effect of electroconvulsive therapy (ECT).

An open study of the effect of a standard course of unilateral ECT applied to 4 patients with intractable thalamic pain. There was no significant change in pain, personality or affective profiles after treatment. Venous plasma endorphins were measured during the ECT course and there were no significant correlations with treatment.

Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg tablet

Nineteen of 25 patients (14 female) with advanced malignant disease completed a randomized controlled trial of a new high-dose (200 mg) tablet formulation of controlled-release morphine. Compared with the currently available 100-mg tablets there were no differences in pain severity or adverse effects with the new formulation. In four patients, full 12-hr plasma morphine concentration profiles at steady state were obtained and showed no significant differences between the same dose provided as 100-mg and 200-mg tablets in Cmax, tmax, or other pharmacokinetic indices.

Case reports - reversal of sensory deficit associated with pain relief after treatment with gabapentin.

&NA; Many patients with neuropathic pain have coexistent sensory deficits. Neuropathic pain may be alleviated by a variety of drugs but sensory deficits are assumed to be permanent. In an audit of the effects of gabapentin therapy on patients with neuropathic pain, monthly detailed sensory examinations were performed during the first three months of treatment. Of five patients with sensory deficits who tolerated gabapentin therapy, three showed marked improvement of their sensory deficits associated with pain alleviation. The cases are presented and possible explanations for the observed sensory improvements are discussed. These findings raised exciting neurophysiological questions in addition to being of potential importance to the clinical problem of neurotrophic tissue injury.

Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol

Abstract Background: Untreated and under-treated pain represent one of the most pervasive health problems, which is worsening as the population ages and accrues risk for pain. Multiple treatment options are available, most of which have one mechanism of action, and cannot be prescribed at unlimited doses due to the ceiling of efficacy and/or safety concerns. Another limitation of single-agent analgesia is that, in general, pain is due to multiple causes. Combining drugs from different classes, with different and complementary mechanism(s) of action, provides a better opportunity for effective analgesia at reduced doses of individual agents. Therefore, there is a potential reduction of adverse events, often dose-related. Analgesic combinations are recommended by several organizations and are used in clinical practice. Provided the two agents are combined in a fixed-dose ratio, the resulting medication may offer advantages over extemporaneous combinations. Conclusions: Dexketoprofen/tramadol (25 mg/75 mg) is a new oral fixed-dose combination offering a comprehensive multimodal approach to moderate-to-severe acute pain that encompasses central analgesic action, peripheral analgesic effect and anti-inflammatory activity, together with a good tolerability profile. The analgesic efficacy of dexketoprofen/tramadol combination is complemented by a favorable pharmacokinetic and pharmacodynamic profile, characterized by rapid onset and long duration of action. This has been well documented in both somatic- and visceral-pain human models. This review discusses the available clinical evidence and the future possible applications of dexketoprofen/tramadol fixed-dose combination that may play an important role in the management of moderate-to-severe acute pain.