The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice.

The present study investigated the effects of pharmacological spinal inhibition of voltage-gated calcium channels (VGCC) in mouse pruritus. The epidural administration of P/Q-type MVIIC or PhTx3.3, L-type verapamil, T-type NNC 55-0396 or R-type SNX-482 VGCC blockers failed to alter the scratching behavior caused by the proteinase-activated receptor 2 (PAR-2) activator trypsin, injected into the mouse nape skin. Otherwise, trypsin-elicited pruritus was markedly reduced by the spinal administration of preferential N-type VGCC inhibitors MVIIA and Phα1ß. Time-course experiments revealed that Conus magus-derived toxin MVIIA displayed significant effects when dosed from 1h to 4h before trypsin, while the anti-pruritic effects of Phα1ß from Phoneutria nigriventer remained significant for up to 12h. In addition to reducing trypsin-evoked itching, MVIIA or Phα1ß also prevented the itching elicited by intradermal (i.d.) injection of SLIGRL-NH2, compound 48/80 or chloroquine, although they did not affect H2O2-induced scratching behavior. Furthermore, the co-administration of MVIIA or Phα1ß markedly inhibited the pruritus caused by the spinal injection of gastrin-releasing peptide (GRP), but not morphine. Notably, the epidural administration of MVIIA or Phα1ß greatly prevented the chronic pruritus allied to dry skin model. However, either tested toxin failed to alter the edema formation or neutrophil influx caused by trypsin, whereas they significantly reduced the c-Fos activation in laminas I, II and III of the spinal cord. Our data bring novel evidence on itching transmission mechanisms, pointing out the therapeutic relevance of N-type VGCC inhibitors to control refractory pruritus.

Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade.

UNLABELLED: We examined the postoperative analgesia of a controlled delivery ketamine transdermal patch after minor abdominal gynecological surgery using lidocaine epidural blockade. Fifty-two patients were randomized to one of two groups. Epidural anesthesia was performed with 25 mL 2% plain lidocaine. At the end of the surgical procedure, a controlled delivery transdermal patch containing either ketamine (25 mg/24 h) (Ketamine group) or placebo (Placebo group) was applied. Pain and adverse effects were assessed hourly postoperatively for 24 h. IM dipyrone was available at patient request. The two groups were demographically similar. The time to first rescue analgesic was longer in the Ketamine group (230+/-112 min) compared with the Placebo group (94+/-54 min); (P<0.00001). There were more dipyrone dose injections in 24 h in the Placebo group compared with the Ketamine group (P<0.0001). The incidence of adverse effects was similar between groups. We conclude that the transdermal-controlled delivery of ketamine prolonged the duration of analgesia after minor gynecological procedures. IMPLICATIONS: Transdermal delivery of ketamine was an useful adjuvant to postoperative analgesia after epidural lidocaine blockade in the population studied.

Intravenous ketamine or fentanyl prolongs postoperative analgesia after intrathecal neostigmine.

The purpose of this study was to determine whether intravenous (i.v.) ketamine would enhance analgesia from intrathecal (IT) neostigmine compared with combining i.v. fentanyl with IT neostigmine. Sixty patients undergoing vaginoplasty under spinal anesthesia were assigned to one of six groups (n = 10). Patients were premedicated with midazolam plus the i.v. test drug. The IT drugs were 20 mg bupivacaine plus saline or 50 micrograms neostigmine. The control group (CG) received saline i.v. and IT. The neostigmine control group (NCG) received saline i.v. and neostigmine IT. The ketamine group (KG) received ketamine 0.2 mg/kg i.v. and saline IT, and the ketamine neostigmine group (KNG), ketamine i.v. and neostigmine IT. The fentanyl group (FG) received fentanyl 1 microgram/kg i.v. and saline IT, and the fentanyl neostigmine group (FNG), fentanyl i.v. and neostigmine IT. The time to first rescue analgesic was longer for the FNG and KNG compared with the CG, with less rescue analgesic consumption (P < 0.02 and P < 0.01, respectively). Only the FNG had significantly intraoperative nausea/vomiting (P < 0.02). In conclusion, the combination of i.v. ketamine and IT neostigmine results in prolonged postoperative analgesia and less intraoperative nausea and vomiting than the combination of i.v. fentanyl and IT neostigmine.