Central Nervous System Sensitization, Hyperalgesia, Pain
Conditions
Keywords
central sensitization, endogenous opioids, humans, latent sensitization, naloxone, open groin hernia repair, pain, randomized controlled trial, secondary hyperalgesia, target-controlled infusion
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.
Interventions
DRUGTarget-controlled naloxone-infusion
DRUGPlacebo
Sponsors
University of Kentucky
National Institute on Drug Abuse (NIDA)
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Denmark
Outcome results
None listed