Pain
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Randomized Controlled Trial Multicenter Study Clinical Trial
Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens.
Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). ⋯ The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.
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Randomized Controlled Trial Multicenter Study Clinical Trial
MorphiDex (morphine sulfate/dextromethorphan hydrobromide combination) in the treatment of chronic pain: three multicenter, randomized, double-blind, controlled clinical trials fail to demonstrate enhanced opioid analgesia or reduction in tolerance.
While many pre-clinical and clinical studies have suggested that the addition of N-methyl-D-aspartate (NMDA) receptor antagonists, such as dextromethorphan (DM), to opioid analgesics, such as morphine (MS), may enhance the analgesic effects and prevent the tolerance that may result from chronic opioid administration, others have not. The potential for reduced doses, enhanced opioid analgesia, and decreased analgesic tolerance associated with the MS/DM combination were evaluated in a series of three large, randomized, double-blind, parallel group, phase 3, multicenter trials each of 3 months duration in patients with chronic, non-malignant, non-neuropathic pain. To evaluate these unique endpoints, novel study designs were employed. ⋯ In Studies B and C, patients self-titrated doses of MS or MS/DM, based on stable doses of MS or other opioids attained during Run-in periods, to maintain pain relief; percentage changes from baseline in MS (or MS-equivalent) doses were compared. No statistically significant differences between treatment groups in any primary or secondary efficacy variables were demonstrated in any trial. These results suggest that adding the NMDA antagonist, dextromethorphan, to opioids does not add any clinical benefit.
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Randomized Controlled Trial Comparative Study Clinical Trial
A 3-year follow-up of a multidisciplinary rehabilitation programme for back and neck pain.
The aim of the present study was to evaluate the long-term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components, compared to a 'treatment-as-usual' control group. The study employed a 4 x 5 repeated-measures design with four groups and five assessment periods during a 3-year follow-up. The group studied consisted of blue-collar and service/care workers on sick leave, identified in a nationwide health insurance scheme in Sweden. ⋯ Regarding sick leave, the mean difference in the per-protocol analysis between the BM programme and the control group was 201 days, thus reducing sick leave by about two-thirds of a working year. Rehabilitating women has a substantial impact on costs for production losses, whereas rehabilitating men seem to be effortless with no significant effect on either health or costs. In conclusion, a full-time behavioural medicine programme is a cost-effective method for improving health and increasing return to work in women working in blue-collar or service/care occupations and suffering from back/neck pain.
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Comparative Study Clinical Trial Controlled Clinical Trial
Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms.
A study was conducted to determine whether changes in expected pain levels, desire for pain relief, or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms. Twenty-six women with IBS were exposed to rectal stimulation (35 or 55 mmHg for 30 s) and tested under natural history (NH), rectal placebo (RP) and rectal lidocaine (RL) conditions. During all conditions, 16 patients were given saline intravenously (to test for a placebo effect) and 10 patients were given naloxone intravenously (to test naloxone antagonism of the placebo effect) on a double blind basis. ⋯ Ratings of expected pain levels, desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session. These changes suggest that a reduction in negative emotions may be central to placebo effects. There was no significant difference between psychological mediators (desire, expectation, anxiety) or the placebo effect in the saline and naloxone groups, indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinically related paradigm.
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The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. ⋯ On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.