The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial Comparative Study
Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.
In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects. ⋯ Few clinical trials focus on patients who are naïve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.
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Randomized Controlled Trial
Activation of naloxone-sensitive and -insensitive inhibitory systems in a human pain model.
We investigated naloxone effects in a model of electrically induced pain and hyperalgesia. In a double-blind, placebo-controlled, cross-over study, 15 volunteers underwent four 150-minute sessions of high-current-density electrical stimulation of their forearms. After 60 minutes, naloxone or placebo was given intravenously (increasing plasma concentrations of 0.1, 1, and 10 ng/mL; 30 minutes each) in 3 of the 4 sessions. Pain ratings and areas of mechanical hyperalgesia were assessed at regular intervals during all sessions. The low doses of naloxone did not cause any significant change of pain rating of areas of hyperalgesia. In terms of intrasession effects, pain ratings and areas of hyperalgesia significantly decreased during the sessions to 62% (pain rating), 70% (area of punctuate hyperalgesia), and 82% (area of allodynia) of the initial values. Naloxone (10 ng/ml) reversed these decreases. In terms of between-session effects, the time course of pain ratings remained constant from session to session. In contrast, the areas of punctate hyperalgesia successively decreased to 60% of initial value at the fourth repetition. The session effect was not reversed by naloxone. High-current-density electrical stimulation provokes central sensitization, but in addition inhibitory systems are activated that are only partly naloxone-sensitive. ⋯ Endogenous inhibitory systems are of major importance for clinical pain conditions, but are not reflected in traditional human pain models. Here we show activation of a naloxone-sensitive short-term and a naloxone-insensitive long-term inhibitory system in a new model of electrically induced pain and hyperalgesia.