Clinical trial NCT01992146: Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Nervous System Sensitization
Pain
Hyperalgesia
Keywords: central sensitization
endogenous opioids
humans
latent sensitization
naloxone
open groin hernia repair
pain
randomized controlled trial
secondary hyperalgesia
target-controlled infusion
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University of Kentucky
name: National Institute on Drug Abuse (NIDA)
First posted: 2013-11-25
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Summated pain intensity
timeFrame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
Secondary outcomes:
measure: Secondary hyperalgesia/allodynia
timeFrame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
measure: Pressure pain thresholds
timeFrame: 1st session: 6-8 weeks; 2nd session: one week later
Other outcomes:
measure: Pain Catastrophizing Scale
timeFrame: in the 1st session: 6-8 weeks after surgery
measure: Hospital Anxiety and Depression Scale
timeFrame: in the 1st session: 6-8 weeks after surgery
measure: Clinical Opiate Withdrawal Scale
timeFrame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
Locations:
city: Copenhagen
country: Denmark
facility: Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Mads U Werner, M.D., D.M.Sc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Mads U Werner, M.D., D.M.Sc.
role: STUDY_DIRECTOR
References:
citation: Papathanasiou T, Springborg AD, Kongstad KT, Staerk D, Moller K, Taylor BK, Lund TM, Werner MU. High-dose naloxone, an experimental tool uncovering latent sensitisation: pharmacokinetics in humans. Br J Anaesth. 2019 Aug;123(2):e204-e214. doi: 10.1016/j.bja.2018.12.007. Epub 2019 Jan 18.
citation: Pereira MP, Werner MU, Dahl JB. Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial. Trials. 2015 Nov 10;16:511. doi: 10.1186/s13063-015-1021-6.