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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Unknown status

CT.gov ID

NCT01992146

Collaborator

University of Kentucky (Other), National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Sensitization Pain Hyperalgesia	Drug: Target-controlled naloxone-infusion Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair. A Randomized, Placebo-controlled, Double-blind Crossover Study

Study Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: Placebo
Experimental: Target-controlled naloxone-infusion (total dose: 3.25 mg/kg) 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.	Drug: Target-controlled naloxone-infusion

Arm

Intervention/Treatment

Placebo Comparator: 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.

Drug: Placebo

Experimental: Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)

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.

Drug: Target-controlled naloxone-infusion

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

Pain Catastrophizing Scale [in the 1st session: 6-8 weeks after surgery]
Patients fill out Pain Catastrophizing Scale before assessments on the first study day
Hospital Anxiety and Depression Scale [in the 1st session: 6-8 weeks after surgery]
Patients fill out Hospital Anxiety and Depression Scale before assessments on the first study day
Clinical Opiate Withdrawal Scale [1st session: 6-8 weeks after surgery; 2nd session: one week later]
Clinical Opiate Withdrawal Scale is filled out before and during naloxone/placebo administration in each experimental session

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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