Effect of Opioids in Neuropathic Pain in Postherpetic Patients

Study Overview
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Brief Summary
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Postherpetic neuralgia (PHN) is often associated with pain and sensory changes and is the leading type of neuropathic pain in modern clinical pain research. It is characterized by a variety of sensory patterns, which may be categorized into irritable nociceptor and impairment of nociceptor. At date, several lines of evidence lead to the assumption, that mechanical hyperalgesia in PHN is based - at least in part - on central nervous processes of sensitization. In animal studies the investigators have discovered a previously unrecognized effect of opioids, the reversal of long-term potentiation (LTP) at C-fibre synapses, i.e. an opioid-induced depotentiation. In principle, synaptic depotentiation may be permanent or transient. In our study the clinically used ultra-short acting MOR agonist remifentanil normalized synaptic strength after wash-out of the drug. At present it is not known whether opioid-induced depotentiation can be used to the benefit of pain patients. The aim is to study the hypothesis, that pain in a group of PHN patients with predominant mechanical hyperalgesia is reversed by intravenous remifentanil at a plasma target concentration of 18ng/ml (corresponding to about 0.75 µg/kg/min) for 60 minutes compared with PHN patients of other sensory types.

Official Title
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Effect of Opioids in Neuropathic Pain in Postherpetic Patients

Conditions
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Neuralgia, Postherpetic

Intervention / Treatment
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* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering from PHN. Pain ≥ 4 out of 10 in numeric rating scale (NRS) Female and male patients above the age of 18 Ability to understand/write/read german Exclusion Criteria: Zoster affecting trigeminal-, opticus region Any somatic pain which is stronger than the neuropathic pain Severe progressive disease Acute cardiac decompensation Known cardiac valve dysfunction Known pulmonary hypertension Cardiac conduction disturbance Active herpetic lesion Opioid therapy Asthma bronchial Chronic obstructive pulmonary disease >GOLD II Severe psychiatric condition Abuse of alcoholic beverages, drug abuse Negative neuropathic symptoms Pregnancy or breast feeding Participation in a clinical trial in the 2 weeks preceding the study Allergy against any medication used in the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Remifentanil|Remifentanil (Ultiva; Glaxo-Smith-Kline; Vienna, Austria) will be applied intravenously during 60 minutes through a dedicated infusion pump (TCI Alaris PK Syringe Pump, Cardinal Health, Baesweiler, Germany), with a Target Controlled Infusion (following the integrated software algorithm by Minto), reaching the initial 18ng/ml plasma concentration in 180 seconds. This corresponds to approx. 0.7 µg kg-1 min-1.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulus-response (SR)-function |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pinprick | Area of secondary hyperalgesia assessed by pinprick | 7 days | 
| Area of dynamic allodynia | Brush, Q Tip, Cotton Wool | 7 days | 
| NRS | Pain according to numeric rating scale (NRS) | 7 days | 
| Mechanical pain threshold | Mechanical pain threshold measured with v. Frey Filaments | 7 days | 
| HPPT | Heat pain perception threshold (HPPT) with thermal sensory analyzer (TSA) | 7 days | 
| HPTT | Heat pain tolerance threshold (HPTT) measured with TSA | 7 days | 
| Coolness | Coolness perception threshold measured with TSA | 7 days | 
| Warmth | Warmth perception threshold measured with TSA | 7 days | 
| LDPI | Laser Doppler Perfusion Imager (LDPI) measuring superficial perfusion of the dermatome | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remifentanil, Hyperalgesia, Zoster, Postherpetic neuralgia