Effect of High Dose Naloxone on Secondary Hyperalgesia

Effect of a High-dose Naloxone Infusion on Secondary Hyperalgesia After a First-degree Burn

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 naloxone (2 mg/kg) can reinstate secondary hyperalgesia 168 hours after a first-degree burn-injury. Investigators aim therefore to show that latent sensitization is present in humans and is modulated by endogenous opioids.

Study Overview

• Status: Completed
• Conditions: Pain; Naloxone; Hyperalgesia; Opioid Antagonist
• Intervention / Treatment: Drug: Placebo; Drug: Naloxone (2 mg/kg)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Dept Anaesthesiology HOC, 4231, Rigshospitalet
  • Copenhagen, Denmark, 2100
    • Multidisciplinary Pain Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy man
• written informed consent
• ASA 1-2
• BMI 18 < BMI < 30
• normal ultrasound examination of the heart
• normal ECG
• urin sample without traces of opioids

Exclusion Criteria:

• volunteers, who do not understand the Danish language
• participation in another experimental trial in the previous 60 days
• nerve damage or skin lesions in the assessment areas
• neurological or psychiatric condition
• use of psycho-active drugs
• abuse of alcohol or drugs
• chronic pain
• regular use of pain-killers (> 1 a week)
• allergy against morphine or other opioids (including naloxone)
• use of prescription drugs 1 week prior to the trial
• use of over-the-counter medication 48 hours prior to the trial
• urin sample with traces of opioids
• volunteer is not suitable for the trial according to the investigator's consideration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; The effect of naloxone (2 mg/kg) on secondary hyperalgesia 168 hours after a first-degree burn-injury is compared to the placebo effect.	Drug: Placebo
Experimental: Naloxone (2 mg/kg); The effect of naloxone (2 mg/kg) on secondary hyperalgesia 168 hours after a first-degree burn-injury is compared to the placebo effect.	Drug: Naloxone (2 mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Secondary hyperalgesia area (cm2) surrounding a first-degree burn injury before and after infusion of naloxone/placebo	Areas of secondary hyperalgesia surrounding a first degree burn-injury will be assessed before and after infusion of naloxone/placebo.	1h, 2h, 3h, 168h, 168h15min, 168h30min post-burn

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in allodynic area (cm2) surrounding a first-degree burn injury before and after infusion of naloxone/placebo	Areas of allodynia surrounding a first degree burn-injury will be assessed before and after infusion of naloxone/placebo.	1h, 2h, 3h, 168h, 168h15min, 168h30min post-burn

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mechanical Pain Thresholds at primary hyperalgesia site before and after naloxone/placebo infusion	Mechanical Pain Thresholds will be assessed with pinprick stimulators at baseline and after infusion of naloxone/placebo at the primary hyperalgesia site (following a first degree burn) and in the contralateral leg.	0h, 168h, 168h30min

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Joergen B Dahl, M.D., DMSc, Dept Anaesthesiology, HOC, 4231, Rigshospitalet; Principal Investigator: Mads U. Werner, M.D., Ph.D., DMSc, Multidisciplinary Pain Center, 7612, Rigshospitalet, Copenhagen

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 19, 2013
• First Submitted That Met QC Criteria: August 30, 2013
• First Posted (Estimate): September 5, 2013

Study Record Updates

• Last Update Posted (Estimate): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 24, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: pain; naloxone; secondary hyperalgesia; allodynia; mechanical pain threshold; endogenous opioids
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: H-2-2012-174