Pain
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Many reports have shown the efficacy of cannabinoid agonists in chronic pain, whereas no report exists concerning the potential effect of cannabinoid antagonists following prolonged treatment. We tested the effects of repeated administration of the selective cannabinoid receptor type 1 (CB1) antagonist, SR141716 (rimonabant), in rats with chronic constriction injury of the sciatic nerve (CCI), an animal model of neuropathic pain. The repeated oral administration of SR141716 (1, 3 and 10 mg/kg, once a day for 1 week, from day 7 after the injury) dose dependently attenuated both thermal and mechanical hyperalgesia. ⋯ This suggests that the compound may favour myelin repair and consequently promote long-lasting functional recovery. This was confirmed by the maintenance of recovery for at least four weeks after treatment discontinuation. In conclusion, the present findings suggest that SR141716 is effective not only in alleviating neuropathic pain but also in favouring the nerve myelin repair.
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Previous work suggests possible relationships between offspring-reported parental history of chronic pain (CP) and offsprings' personal chronic pain experience. This study examined reliability of offsprings' reports of parental CP history based on direct comparison with confirmed parental reports. Participants included 108 male and female college students who completed a questionnaire assessing presence/absence and locations of any past or present CP lasting greater than 3 months. ⋯ Results indicated that these relationships were not mediated by social desirability, negative affect, or catastrophizing cognitions. In contrast to results for offspring-reported data, confirmed parental CP history reports failed to predict offsprings' personal CP history. These results raise questions as to the validity of previous findings of relationships between family pain history and individuals' own experience of CP.
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Chronic pain following whiplash injury and non-specific arm pain (NSAP, previously termed diffuse repetitive strain injury) present clinicians with problems of diagnosis and management. In both patient groups there are clinical signs of altered nerve movement and increased nerve trunk mechanosensitivity. Previous studies of NSAP patients have identified altered median nerve movement at the wrist. ⋯ In the whiplash patients the pattern of transverse median nerve movement at the proximal carpal tunnel was significantly different to controls (patient mean=2.57+/-0.80 mm (SEM) in a radial direction; control mean=0.39+/-0.52 mm in an ulnar direction). Signs of neural mechanosensitivity (i.e. painful responses to median nerve trunk and brachial plexus pressure and stretch) were apparent in both patients groups. Change in nerve tension and neural mechanosensitivity may contribute to symptoms in whiplash and NSAP patients.
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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.