Prediction of Inter-individual Differences in the Response to Morphine Versus Milnacipran in Patients With Sciatica

Study Overview
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Brief Summary
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Clinical, psychophysical, behavioral or genetic factor will predict the response to opioid treatment in patients with chronic neuropathic pain.

Official Title
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Prediction of Inter-individual Differences in the Response to Morphine by Psychophysical Assessment of Pain Enhancing and Inhibiting Mechanisms in Patients With Chronic Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: Morphine
* Drug: Milnacipran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with moderate to severe chronic neuropathic pain or patients with radiculitis between 18 and 75 years of age. Candidates for chronic opioid therapy for nonmalignant pain as determined by treating physician. Patients treated with non-opioid analgetics, anti- inflammatory drugs or low opioid dosage (< 30 mg of oral morphine-equivalents per day). Ability to understand the purpose and instructions of the study and to sign an informed consent. - Exclusion Criteria: 1.Diabetic Neuropathy 2.Pain in upper limbs 3.Receiving anti- depressants and/or anticonvulsants 4.Pregnant women 5.Inability to comply with study protocol. 6.Allergy to Opioids 7.A diagnosis of Raynaud's Syndrome 8.History of substance abuse -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morphine<br>Morphine in changing dosages (range between 10-60 mg twice a day). Opioid titration proceeds as follows: starting at an oral dose of 10 mg twice per day, followed every 5 days by a dose increase of 10 mg twice per day until (1) adequate analgesia had been achieved (as determined by the patients), (2) side effects (severe sedation, nausea or vomiting, constipation, sleep disturbances) limited further titration, or (3) a total of 120 mg per day had been reached. | Drug: Morphine<br> <br> |
| Active Comparator: Milnacipran<br>Milnacipran (Ixel)- a serotonin-norepinephrine reuptake inhibitor (SNRI), will be administrated in changing dosages (range between 12.5-75 mg twice daily). SNRI titration proceeds as follows: starting at an oral dose of 12.5 mg twice per day, followed every 5 days by a dose increase of 12.5 mg twice per day until (1) adequate analgesia had been achieved (as determined by the patients), (2) side effects (severe sedation, nausea or vomiting, constipation, sleep disturbances) limited further titration, or (3) a total of 150 mg per day had been reached. | Drug: Milnacipran<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic pain intensity (NPS) |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat pain intensity in a remote area (Opioid induced hyperalgesia) | Heat pain sensitivity will be determined by the use of VAS units (0-100). We'll measure the intensity of pain in response to application of brief experimental heat pain. | 1 month | 
| The McGill Pain Questionnaire | Will be completed before and after treatment | At baseline and at the end of 4-week treatment period | 
| Assessment of Adverse events | A list of possible side effects from the administered drugs has been prepared and will be completed at all scheduled visits. In addition, patients will record AEs on daily basis. If needed patients can call and report adverse events by phone. | Ongoing throughout the entire study period, an expected average of 4 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid induced hyperalgesia, Neuropathic pain, Opioids, Sciatica, Serotonin-norepinephrine reuptake inhibitor (SNRI)