(214) Rofecoxib Provides Superior Relief of Pain in Osteoarthritis (OA) Compared to Celecoxib.

We performed a randomized, double-blind, clinical trial to evaluate pain relief efficacy of rofecoxib and celecoxib at highest indicated once daily doses in osteoarthritis. 1082 patients meeting entry criteria for OA, responsive to NSAIDs, were randomized 3:3:1 to treatment with rofecoxib 25 mg QD (n = 471), celecoxib 200 mg QD (n = 460) or placebo (n = 151). Efficacy was assessed over the first 6 days of therapy and at weeks 2, 4 and 6 by WOMAC questionnaire and patient global assessment of response to therapy (PGART). Demographics were well balanced. Significantly more patients on placebo discontinued prematurely compared to both active groups (p < 0.001) mainly due to lack of pain relief efficacy. Rofecoxib provided statistically superior relief of night pain (p = 0.023), morning stiffness (p = 0.002), rest pain (p = 0.023), and walking pain (p = 0.005) compared to celecoxib. Rofecoxib was significantly superior to celecoxib on all WOMAC subscales including pain (p = 0.008), stiffness (p = 0.001) and physical function (p = 0.01). Rofecoxib was superior to celecoxib in % of patients with good or excellent PGART over 6 weeks (p = 0.014) and provided quicker onset of pain relief as assessed by time to first report of good or excellent response (p < 0.001). Both active groups were superior to placebo on efficacy endpoints. Incidence of clinical AEs, drug related AEs, serious AEs, and discontinuations due to AEs was similar between active groups. In this study, once daily doses of rofecoxib provided superior relief of pain and other related symptoms in OA compared to celecoxib and placebo. All treatments were generally well tolerated.

The effect of peripheral glycerol on trigeminal neuropathic pain examined by quantitative assessment of abnormal pain and sensory perception.

In nine patients with trigeminal neuropathic pain after nerve injury, we examined prospectively the effect of peripheral glycerol neurolysis on abnormal pain and sensory perception. In the painful facial skin area of these patients, we found increased temperature and tactile thresholds and the presence of abnormal temporal summation of pain. In seven patients, neuropathic pain was peripheral and disappeared after application of local anaesthesia at or proximal to the site of nerve injury. Neuropathic pain was central in two patients, and unresponsive to local anaesthesia applied proximal to the site of nerve injury. Six weeks after injection of glycerol proximal to the site of nerve injury, no or marginal pain relief was found in 8 patients with peripheral or central trigeminal neuropathic pain. On the other hand, in one of the patients with peripheral trigeminal neuropathic pain, glycerol was given at the site of nerve injury, and produced total pain relief for the whole observation period of 7 months. In this patient, pain relief was associated with normalisation of abnormal temporal summation of pain, which was not observed in the 8 patients with no or marginal pain relief. No further changes in temperature or tactile thresholds were found in any of the 9 patients after a single injection of absolute glycerol. Total pain relief in one of the patients probably is related to the ability of glycerol to inhibit ongoing ectopic impulse generation at the site of nerve injury. We suggest that glycerol-induced reduction of primary afferent hyperactivity may secondarily result in down-regulation of central neuronal hyperexcitability. The efficacy of application of glycerol at the site of nerve injury in patients with peripheral trigeminal neuropathic pain may warrant further investigation. However, this prospective study does not provide evidence that application of glycerol proximal to the site of nerve injury has a place in the treatment of trigeminal neuropathic pain.

Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination.

As part of a study to evaluate the analgesic efficacy of meperidine and hydroxyzine, alone and in combination, a double-blind complete crossover study of meperidine (50 mg IM), hydroxyzine (100 mg IM), meperidine (50 mg IM) plus hydroxyzine (100 mg IM), and saline placebo was conducted. Thirty patients with chronic moderate to severe pain due to metastatic cancer were evaluated as to pain relief following administration of all four study medications. All of the treatment groups showed statistically significant analgesic activity as compared to placebo. Hydroxyzine provided sustained pain relief to six hours, whereas meperidine produced analgesia up to two hours. The combination produced additive analgesia only during the first 2 hr. The pharmacokinetics of meperidine and hydroxyzine were compared to observed analgesia. Significant correlation between serum drug levels of meperidine and hydroxyzine and pain relief resulted and the serum levels of meperidine and hydroxyzine necessary for analgesia were calculated to be 0.10-0.15 mg/ml and 60-70 ng/ml; respectively. The observed analgesia of the meperidine/hydroxyzine combination was correlated with the analgesia of the individual agents and the limited additive analgesia observed with the addition of meperidine to hydroxyzine does not justify the added toxicity of the narcotic.

Effective pain relief with continuous intrapleural bupivacaine after thoracotomy in infants and children.

The effect of continuous intrapleural bupivacaine on pain relief after lateral thoracotomy was studied in nine infants (< or = 15 kg body weight) and 11 children (> 15 kg body weight). An intrapleural catheter was inserted under direct vision during surgery. After extubation, the patients were transferred to the ICU where vital signs and pain scores were monitored. An intrapleural infusion of bupivacaine 0.25% with adrenaline was given at a loading dose of 0.625 mg.kg-1 body weight followed by a continuous infusion with a starting rate of 1.25 mg.kg-1.h-1. Haemodynamic and respiratory parameters did not differ significantly from control values throughout the study period in either group. The mean infusion rate could be reduced stepwise in both groups to 0.75 +/- 0.32 mg.kg-1.h-1 and 0.73 +/- 0.38 mg.kg-1.h-1 respectively. The pain score indicated a rapid onset of analgesia in both groups and remained low during the study period. The degree of analgesia amongst other factors was position dependent. The lack of any recognizable side effects or complications related to this method has been most encouraging. Only one child required a supplementary dose of an opioid. We conclude that continuous intrapleural access has proved to be a safe and suitable route for pain relief in infants and children following thoracotomy.