Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair.

Phase 2

Completed

• Conditions: Central Nervous System Sensitization; Hyperalgesia; Pain
• Interventions: Drug: Placebo; Drug: Target-controlled naloxone-infusion

• Registration Number: NCT01992146
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-07
• Study First Submitted QC: 2013-11-18
• Study First Posted: 2013-11-25
• Study Start: 2015-11-11
• Primary Completion: 2015-12-14
• Study Completion: 2018-05-11
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 9

Inclusion Criteria

• Age ≥ 18 years and ≤ 65 years
• Signed informed consent
• Patients submitted to unilateral, primary inguinal, open herniotomy 6-8 weeks prior to study start.
• Open operating procedure a.m. Lichtenstein.
• Urin sample without traces of opioids (morphine, methadon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphine, dextromethorphan)
• ASA I-II
• Body mass index (BMI): 18 < BMI < 30

Exclusion Criteria

• Volunteers , who do not speak or understand Danish
• Patients, who cannot cooperate with the investigation
• Patients who have had previous surgery in the groin region
• Patients with pain at rest > 3 (NRS)
• Activity-related pain in the surgical field > 5
• Allergic reaction against morphine or other opioids (including naloxone),
• Abuse of alcohol or drugs - according to investigator's evaluation
• Use of psychotropic drugs (exception of SSRI)
• Neurologic or psychiatric disease
• Chronic pain condition
• Regular use of analgesic drugs
• Skin lesions and tattoos in the assessment areas
• Nerve lesions in the assessment sites (for instance, after trauma, disc herniation, etc.)
• Use of prescription drugs 1 week before the trial
• Use of over-the-counter drugs 48 hours before the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Change in Pain Ratings (NRS) at the surgical site and at the mirror-site in the contralateral groin six to eight weeks after unilateral herniotomy following administration of placebo.
Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)	Target-controlled naloxone-infusion	Change in Pain Ratings (NRS) at the surgical site and at the mirror-site in the contralateral groin six to eight weeks after unilateral herniotomy following administration of naloxone.

Primary Outcome Measures

Name	Time	Method
Summated pain intensity	1st session: 6-8 weeks after surgery; 2nd session: one week later	Change in pain ratings (\[NRS,0-10\] pain at rest + pain during transition from supine to standing position + pain during pressure (100 kPa) at injury site), assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.

Secondary Outcome Measures

Name	Time	Method
Secondary hyperalgesia/allodynia	1st session: 6-8 weeks after surgery; 2nd session: one week later	Change in secondary hyperalgesia area/allodynia at surgical site and at the mirror-site in the contralateral groin assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.
Pressure pain thresholds	1st session: 6-8 weeks; 2nd session: one week later	Change in pressure pain thresholds at surgical site and at the mirror-site in the contralateral groin assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.

Trial Locations

Locations (1)

Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet; 🇩🇰 Copenhagen, Denmark