piperidines and parecoxib

Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double-blind, placebo-controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib+remifentanil, and ketorolac+remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30-minute infusion of either remifentanil or saline. The cold-pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P < 0.001 and P = 0.005, respectively). Pretreatment with parecoxib or ketorolac reduced the postinfusion area of pinprick hyperalgesia (P < 0.001 and P = 0.001, respectively), compared to the remifentanil group. Parecoxib reduced the area significantly more than ketorolac (P = 0.009). In the CPT, pretreatment with parecoxib or ketorolac did not prevent postinfusion hyperalgesia. These results demonstrated OIH in both models, and may suggest that COX-2 inhibition is more important than COX-1 inhibition in reducing hyperalgesia. Remifentanil-induced hyperalgesia was demonstrated for both electrically induced pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.

Topics: Adult; Analgesics, Opioid; Blood Pressure; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Drug Interactions; Humans; Hyperalgesia; Isoxazoles; Ketorolac; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Physical Stimulation; Piperidines; Remifentanil; Time Factors; Young Adult

Numerous experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. It is suggested that spinal cyclooxygenase activity may contribute to the development and expression of opioid tolerance. The aim of the investigation was to determine analgesic and antihyperalgesic properties of the cyclooxygenase-2 inhibitor parecoxib on remifentanil-induced hypersensitivity in humans.. Fifteen healthy male volunteers were enrolled in this randomized, double-blind, placebo-controlled study in a crossover design. Transcutaneous electrical stimulation at high current densities was used to induce spontaneous acute pain (numeric rating scale 6 of 10) and stable areas of pinprick hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during, and after a 30-min intravenous infusion of remifentanil (0.1 microg x kg x min) or placebo (saline). Parecoxib (40 mg) was administered intravenously either with onset of electrical stimulation (preventive) or in parallel to the remifentanil infusion.. Remifentanil reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level. Preventive administration of parecoxib led to an amplification of remifentanil-induced antinociceptive effects during the infusion (71.3 +/- 7 vs. 46.4 +/- 17% of control) and significantly diminished the hyperalgesic response after withdrawal. In contrast, parallel administration of parecoxib did not show any modulatory effects on remifentanil-induced hyperalgesia.. The results confirm clinically relevant interaction of mu opioids and prostaglandins in humans. Adequate timing seems to be of particular importance for the antihyperalgesic effect of cyclooxygenase-2 inhibitors.

Topics: Adult; Analgesia; Analgesics, Opioid; Cyclooxygenase Inhibitors; Double-Blind Method; Drug Interactions; Humans; Hyperalgesia; Infusions, Intravenous; Isoxazoles; Ketamine; Male; Middle Aged; Pain Threshold; Piperidines; Remifentanil

Nano-carbon is often used as a tracer in thyroidectomy, to improve the accuracy of the operation. Remifentanil is the most commonly used anesthetic during thyroidectomy, but the use of remifentanil can sometimes cause patients with anesthesia hyperalgesia. Therefore, auxiliary anesthetics are often used in surgery to prevent remifentanil from causing anesthesia hyperalgesia. The purpose of this article is to explore the specific application effect of the fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon in the prevention of remifentanil-induced anesthesia hyperalgesia. Taking 60 patients who underwent thyroidectomy based on carbon nanotechnology in our hospital as the research object, the patients were divided into the parecoxib sodium group, hydromorphone control group and hydromorphone and parecoxib sodium fusion agent group. All patients were injected with remifentanil before surgery for general paralysis. Ten minutes before the end of the operation, the parecoxib sodium group was injected with quantitative parecoxib sodium, and the hydromorphone control group was injected with quantitative hydromorphone, hydromorphone and the parecoxib sodium fusion medicament group was injected with a quantitative combination of parecoxib sodium and hydromorphone. The patient's comfort, calmness, pain, adverse reactions and recovery time of consciousness were counted. The results of the study showed that the sedation score of the hydromorphone and parecoxib sodium fusion drug group was (15.8±1.5), the pain degree score was (1.9±0.5), lower than the other two groups, and the postoperative recovery time was (38±5.0) )min, lower than the other two groups. It can be seen that the use of a fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon is effective in preventing and reducing remifentanil-induced anesthesia hyperalgesia.

Topics: Analgesics, Opioid; Anesthesia; Humans; Hydromorphone; Hyperalgesia; Isoxazoles; Pain; Piperidines; Remifentanil; Thyroidectomy