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

Rigshospitalet

Status and phase: Completed; Phase 2

Conditions: Central Nervous System Sensitization; Hyperalgesia; Pain

Treatments: Drug: Target-controlled naloxone-infusion; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01992146

MP_SM01_2013

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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9 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: Target-controlled naloxone-infusion