Spread of Muscle Hyperalgesia and Pain in a Low Dose NGF-induced Pain Model

Study Overview
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Brief Summary
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The purpose of this study is to investigate and determine the time course and distribution on muscle hyperalgesia and muscle pain in a repeated, low dose NGF model. It is hypothesized that low dosages i.m injections of NGF are able to induce mechanical hyperalgesia and muscle soreness in a same manner (effect of duration) as for dosages previously used in NGF studies. Furthermore, it is also speculated if several injections of low dose NGF into the muscle combined are able to course immediate pain sensation and spreading of muscle hypersensitivity.

Detailed Description
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Effects of pain responses, symptom development and pattern (time course and distribution) following 5 i.m low dose injections of NGF injected into the tibialis anterior muscle will be compared to a high dose i.m injection of NGF injected into the contralateral side in healthy pain-free subjects.

Official Title
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Spread of Muscle Hyperalgesia and Pain in a Low Dose NGF-induced Pain Model

Conditions
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Hyperalgesia, Healthy Subjects

Intervention / Treatment
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* Drug: NGF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy and pain free volunteers Exclusion Criteria: Pregnancy Drug addiction defined as the use of cannabis, opioids or other drugs Previous neurologic, mental illnesses, or psychiatric diseases. Past history of chronic pain in the musculoskeletal system (muscle, joint, cartilage, connective tissue) Participation in other pain trials throughout the study period Lack of ability to cooperate Taking any analgesic 24 hours before the injections Performing any strenuous leg exercise through out the study period causing sore muscles

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>All participants will receive 5 i.m injections of NGF (1 ug/0.5ml) into the tibialis anterior muscle (either left or right leg) | Drug: NGF<br>* Intramuscular injection<br>* Other names: Beta-Nerve Growth Factor, Human;|
| Experimental: High dose<br>All participants will receive 1 high dose i.m bolus injection of NGF (5 ug/0.5ml) and 4 injections of saline (control/same volume) into the tibialis anterior muscle (either left or right leg) | Drug: NGF<br>* Intramuscular injection<br>* Other names: Beta-Nerve Growth Factor, Human;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle sensitivity | Pressure pain thresholds (PPTs) are assessed over the tibialis anterior muscles using a handhold pressure algometer. | Change from baseline at 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure-induced referred pain | At three predetermined sites within the tibialis anterior muscle, a constant pressure stimulation (120% of PPT) is evoked by use of the pressure algometer. Subjects color their perceived sensation of pain on an electronic schematic of the lower legs using Navigate Pain. | Change from baseline at 3 weeks | 
| Activity-induced muscle soreness | Subjects perform 10 dorsiflexions with each leg. The perceived muscle soreness is reported using a numeric rating scale (NRS) and the area of soreness is colored on an electronic schematic of the lower legs (Navigate Pain). | Change from baseline at 3 weeks | 
| Pain intensity | Subjects rate their perceived pain intensity on a visual analogue scale (VAS) App (Aalborg University) as displayed on a tablet computer with a sample rate of 1 Hz. | Assessed continuously at 0-5 min during the injections at each leg | 
| Muscle soreness Diary | Two times a day subjects evaluate their muscle soreness using a Likert Scale of muscle soreness for lower limp | Change from baseline at 3 weeks | 
| Activity-induced muscle soreness Diary | Subjects perform 10 dorsiflexions with each leg. The perceived muscle soreness is reported using a numeric rating scale (NRS) and the area of soreness is colored on an electronic schematic of the lower legs (Navigate Pain). The activity is performed at home on days in between the sessions | Change from baseline at 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle soreness, NGF-induced pain, Pain model, Long-lasting sensitization