Track topics on Twitter Track topics that are important to you
Recent studies have focused on the role of endogenous opioids on central sensitization. Central sensitization is known to be impaired or altered in chronic pain conditions, as fibromyalgia or chronic tension headache.
Animal studies have shown reinstatement of mechanical hypersensitivity following naloxone administration after resolution of an injury. This suggests latent sensitization. In the present study, investigators hypothesize that a high-dose target-controlled naloxone infusion (total dose: 3.25 mg/kg) can reinstate pain and hyperalgesia 6-8 weeks after a unilateral primary open groin hernia repair procedure. Investigators aim to show that latent sensitization is present in humans and is modulated by endogenous opioids.
Naloxone is a combined mu-opioid-receptor (MOR) inverse agonist and antagonist drug, which dose-dependently demonstrates hypoalgesic and hyperalgesic properties. Systemically administrated naloxone (3.0-10.0 mg/kg) and naltrexone (0.3-3.0 mg/kg) have been used in rodents to study the role of endogenous opioids on central processing of pain. It has been hypothesized that the endogenous opioid modulation of pain is impaired or altered in chronic pain conditions. Administration of naloxone and naltrexone following resolution of an inflammatory injury, have demonstrated a reinstatement of hypersensitivity to noxious stimuli, indicating a demasking of latent sensitization. It has thus been speculated that the endogenous opioid system may play an important role in the transition of acute to chronic pain in humans.
In an early human study using an electrical pain model, naloxone (21 microg/kg) increased the established area of secondary hyperalgesia (a measure of central sensitization).
In a previous translational placebo-controlled, double-blind, randomized, cross-over study in healthy humans, we were unable to show naloxone-induced reinstatement of secondary hyperalgesia after resolution of a first-degree burn-injury (BI; H-2-2012-036). We hypothesized, that the negative results were attributable to the low dose of naloxone (21 microg/kg) or perhaps insufficient tissue injury to generate latent sensitization.
We therefore in a sequel study administered a higher dose of naloxone (2 mg/kg) 7 days after induction of a BI. We demonstrated in 4 out of 12 subjects reinstatement of secondary hyperalgesia. The magnitude of reinstatement was more pronounced in high-sensitizers (subjects developing large secondary hyperalgesia areas immediately after the BI) The aims of the present clinical study in patients are first, to replicate our previous findings of naloxone-induced (3.25 mg/kg) unmasking of latent sensitization utilizing the impacted mandibular third molar extraction (TME) model with a more pronounced tissue injury than the BI-model. The endpoints are reinstatement of pain and hyperalgesia in the resolution-phase, 4 - 5 wks. after TME-surgery. Second, the study examines a potential dose-response relationship between three stable naloxone concentrations acquired by target controlled infusion (TCI).
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Naloxone, Normal Saline
Neuroscience Center, Copenhagen University Hospital
Not yet recruiting
University of Copenhagen
Published on BioPortfolio: 2016-11-30T15:45:31-0500
Brain-dead patients who provide authorization for organ donation will be randomized to naloxone or placebo if baseline arterial blood gas (ABG, after initiation of OPO management) reveals ...
The purpose of this study is to determine whether the analgetic and other effects effect of ketamine are partly mediated through opioid receptors
Endorphins are naturally occurring narcotic substances that are released when individuals perform exercise. The hypothesis of the study is that endorphins reduce the severity of breathles...
Endorphins are released in response to breathing difficulty and can modify the perception of breathlessness. In this randomized placebo-controlled trial, resistive breathing loads are used...
This is a single center, single-blind randomized cross over design trial that will compare the impact of intra-nasal naloxone vs. intra-nasal saline administration during experimental hypo...
To compare the effects of 3% hypertonic saline (HS) and 0.9% normal saline with nebulized 0.9% normal saline with salbutamol in patients of acute viral bronchiolitis.
Few studies have described the characteristics of metabolically healthy individuals with excess fat in the Chinese population. This study aimed to prospectively investigate the natural course of metab...
The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced imm...
Given the potential to expand naloxone supply through community pharmacy, the aim of this study was to estimate Australian pharmacists': (1) level of support for overdose prevention, (2) barriers and ...
Mounting evidence suggests that not all obese subjects are at increased cardiovascular risk. However, the relationship between the metabolically healthy obese (MHO) phenotype and cardiovascular diseas...
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
A genus of HALOBACTERIACEAE distinguished from other genera in the family by the presence of specific derivatives of TGD-2 polar lipids. Haloarcula are found in neutral saline environments such as salt lakes, marine salterns, and saline soils.
A family of gram-negative, moderately halophilic bacteria in the order Oceanospirillales. Members of the family have been isolated from temperate and Antarctic saline lakes, solar salt facilities, saline soils, and marine environments.
Books intended for use in the study of specific subjects, containing systematic presentation of the principles and essential knowledge of the subjects.
A type of analysis in which subjects in a study group and a comparison group are made comparable with respect to extraneous factors by individually pairing study subjects with the comparison group subjects (e.g., age-matched controls).