Milnacipran Has an Antihyperalgesic Effect on Cisplatin-Induced Neuropathy.

(1) Background: Milnacipran is a typical serotonin-norepinephrine reuptake inhibitor and has been shown to have analgesic effects in several pain models. However, its antihyperalgesic effect in cisplatin-induced neuropathy remains unknown. We examined the effects of intraperitoneal (IP) milnacipran on allodynia in cisplatin-induced peripheral neuropathic mice. (2) Methods: Peripheral neuropathy was induced by injecting cisplatin (2.3 mg/kg/day, IP) six times, on every other day. Saline or milnacipran (10, 30, 50 mg/kg, IP) were then administered to the neuropathic mice. We examined mechanical allodynia using von Frey hairs at preadministration and at 30, 60, 90, 120, 180, 240 min and 24 h after drug administration. We also measured the dorsal root ganglion (DRG) activating transcription factor 3 (ATF3) to confirm the analgesic effects of milnacipran. (3) Results: For the milnacipran groups, the decreased paw withdrawal thresholds to mechanical stimuli were significantly reversed when compared to the preadministration values and the values in the saline-injected control group (p < 0.0001). Milnacipran administration to cisplatin-induced peripheral neuropathic mice resulted in a significant suppression of neuronal ATF3 activation (p < 0.01). (4) Conclusions: Milnacipran given via IP injection attenuates mechanical allodynia in mouse models of cisplatin-induced poly-neuropathic pain. These effects were confirmed by significant suppression of neuronal ATF3 activation in the DRG.

The effect of a continuous infusion of low-dose esmolol on the requirement for remifentanil during laparoscopic gynecologic surgery.

STUDY OBJECTIVE: To investigate whether a continuous infusion of low-dose esmolol results in an opioid-sparing effect during surgery. DESIGN: Randomized, double-blinded, placebo-controlled clinical comparison study. SETTING: Operating room of a university hospital. PATIENTS: 56 ASA physical status 1 and 2 patients, aged 20 to 60 years, undergoing laparoscopic gynecologic surgery of less than two hours' duration. INTERVENTIONS: The esmolol group (n = 28) received a 0.5 mg/kg loading dose of esmolol followed by an infusion of esmolol 30 µg/kg/min; the saline group (n = 28) received equivalent volumes of normal saline. MEASUREMENTS: The effect-site concentration of remifentanil (ng/mL) to maintain adequate anesthetic depth before infusion of the study drug (before-concentration) was measured. During infusion of study drug, the effect-site concentration of remifentanil was adjusted every 5 minutes to maintain systolic blood pressure within 15% of baseline and a Bispectral Index value between 50-60. The average of these adjusted concentrations (after-concentration) was measured and compared to the before-concentration. The quality of postoperative recovery was assessed. MAIN RESULTS: In the esmolol group, the after-concentration of remifentanil was decreased by 33.3% compared with the before-concentration. The total dose of remifentanil infused was also lower in the esmolol group (0.09 ± 0.1 vs 0.14 ± 0.03 µg/kg/min; P = 0.031). The esmolol group had lower scores on a pain numerical rating scale and required less fentanyl in the Postanesthesia Care Unit. CONCLUSIONS: Intraoperative esmolol infusion decreases both the requirement for remifentanil and postoperative administration of rescue analgesics.