naloxone and Hernia--Inguinal

Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans.. Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6-8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276).. We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies.. 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014).

Topics: Analgesics, Opioid; Central Nervous System Sensitization; Clinical Protocols; Cross-Over Studies; Denmark; Double-Blind Method; Drug Monitoring; Hernia, Inguinal; Herniorrhaphy; Humans; Hyperalgesia; Infusions, Parenteral; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold; Pain, Postoperative; Research Design; Treatment Outcome

A 60-year-old man without comorbidity underwent a totally extraperitoneal repair of bilateral inguinal hernias under general anesthesia. Forty minutes after the procedure he developed a slow, shallow respiratory pattern with a respiratory rate of 5/min and a self-limiting grand mal seizure lasting 30 seconds. Arterial blood gas analysis indicated significant hypercarbia and acidosis. The total dose of morphine administered was 20 mg intravenously. Naloxone was administered and the respiratory rate improved. The patient was discharged after 24 hours after making a good recovery and has had no further seizures a year after surgery. Although hypercarbia is a well-known complication of laparoscopic surgery when CO2 is used for insufflation, this, to the best of our knowledge, is the first reported case of a patient sustaining a grand mal seizure resulting from CO2 narcosis after laparoscopic surgery. The possible mechanisms are discussed.

Topics: Blood Gas Analysis; Carbon Dioxide; Epilepsy, Tonic-Clonic; Hernia, Inguinal; Humans; Laparoscopy; Male; Middle Aged; Naloxone; Narcotic Antagonists; Postoperative Complications; Stupor

Topics: Adult; Anesthesia, Epidural; Anesthetics, Local; Epinephrine; Female; Hernia, Inguinal; Humans; Morphine; Naloxone; Respiratory Insufficiency