Evaluation of the Role of the Noradrenergic System in Pain Perception in Parkinson's Disease

Study Overview
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Brief Summary
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Patients suffering from Parkinson's disease (PD) frequently experienced painful sensations that could be, in part, due to a central modification of nociception mechanisms. Previous studies have shown that pain perception was altered in Parkinson's disease (subjective and objective pain thresholds and pain-induced cerebral activity) and that administration of L-Dopa normalized this alteration. In the central nervous system, L-Dopa is converted in dopamine and in norepinephrine. Apomorphine (a dopamine agonist) has no effect on pain threshold and pain-induced cerebral activity. Therefore the noradrenergic system could be involved in pain alteration in PD. To assess the role of noradrenergic system in pain in patients with PD, we chose duloxetine (norepinephrine and serotonin reuptake inhibitor)because a recent study had shown that duloxetine allowed an improvement of pain clinical scores (pain questionnaires) in patients with PD. 36 patients will be enrolled in this study. We supposed that a chronic intake of duloxetine increase the pain perception level compare to the placebo. This increase would be the same than those observed with L-Dopa.

Official Title
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Evaluation of the Role of the Noradrenergic System in Pain Perception in Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: duloxetine
* Drug: placebo of duloxetine
* Drug: injection of apomorphine
* Drug: injection of placebo of apomorphine
* Drug: L-Dopa
* Drug: injection of placebo of L-Dopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinical diagnosis of Parkinson's disease according to the criteria of the UKPDSBB Parkinson's disease patients with a score ≤ 3 on the Hoehn and Yahr scale Patients treated with dopaminergic antiparkinsonian drugs (L-Dopa, dopamine agonists, ICOMT…) Patients affiliated to a social protection program Women with efficacy contraception Exclusion Criteria: Patients suffering from another pathology causing chronic pain (rheumatic disease, traumatic or orthopedic pathologies…) Parkinson's disease patients with a score > 3 on the Hoehn and Yahr scale Depressed patients (MADRS score < 16) Patients suffering from a cancer Patients under tutelage, curatella or law protection Patients with a complete contraindication against apomorphine injections or duloxetine administration (selective serotonin reuptake inhibitor and monoamine oxydase inhibitors) Patients without any control of their arterial hypertension Patients with a neuroleptic treatment Pregnant women

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: duloxetine<br>The first group (12 patients) will receive, after 28 days of duloxetine treatment, one duloxetine dose, an injection of apomorphine and a placebo of L-Dopa. | Drug: duloxetine<br>* administration during 28 days<br>Drug: injection of apomorphine<br>* injection performed at D28<br>Drug: injection of placebo of L-Dopa<br>* performed at D28<br>|
| Placebo Comparator: positive control (L-Dopa)<br>The second group (12 patients) will receive, after 28 days of placebo treatment, one placebo dose of duloxetine, an injection of apomorphine and injection of placebo of L-Dopa. | Drug: placebo of duloxetine<br>* administration during 28 days<br>Drug: injection of apomorphine<br>* injection performed at D28<br>Drug: injection of placebo of L-Dopa<br>* performed at D28<br>|
| Placebo Comparator: negative control<br>The third group will receive, after 28 days of placebo treatment, one placebo of duloxetine, an injection of placebo of apomorphine and a dose of L-Dopa. | Drug: placebo of duloxetine<br>* administration during 28 days<br>Drug: injection of placebo of apomorphine<br>* performed at D28<br>Drug: L-Dopa<br>* performed at D28<br>* Other names: injection of L-dopa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective pain threshold determined using thermal stimulations (thermotest) with the method of levels | Before duloxetine intake and after one month of chronic duloxetine intake | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective pain threshold determined recording the nociceptive reflex of flexion | Before duloxetine intake and after one month of chronic duloxetine intake | One month | 
| Clinical evaluation of the severity of the motor handicap of patients using the Unified Parkinson's Disease Rating Scale (UPDRS III) | Before duloxetine intake and after one month of chronic duloxetine intake | One month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Noradrenergic system and pain in Parkinson's disease