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

Study Overview
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Brief Summary
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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.

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

Conditions
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Central Nervous System Sensitization, Pain, Hyperalgesia

Intervention / Treatment
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* Drug: Target-controlled naloxone-infusion
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br> <br> |
| Experimental: Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summated pain intensity | 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. | 1st session: 6-8 weeks after surgery; 2nd session: one week later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary hyperalgesia/allodynia | 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. | 1st session: 6-8 weeks after surgery; 2nd session: one week later | 
| Pressure pain thresholds | 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. | 1st session: 6-8 weeks; 2nd session: one week later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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central sensitization, endogenous opioids, humans, latent sensitization, naloxone, open groin hernia repair, pain, randomized controlled trial, secondary hyperalgesia, target-controlled infusion