Exercise-induced Ischemia and the Influence of Pain Modulation in a Nerve Growth Factor (NGF) Model

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate responses of pain and the maintenance of mechanical muscle hypersensitivity following an acute exercise-induced ischemic condition repeated over time in a prolonged NGF-sensitized muscle. Additionally, the influence of the pain modulating system on prolonged NGF muscle hypersensitivity caused by peripheral mechanisms and central mechanisms will also be investigated.

Detailed Description
-----------------
The hypothesis is that an ischemic conditioning in a NGF-sensitized muscle is able to facilitate pain responses and that over time the pain modulation system is responsible for a subsequent reduction in muscle sensitivity towards mechanical pressure and a decrease in pain intensity following a period of NGF-induced muscle hypersensitivity.

Official Title
-----------------
Interaction Between NGF and Exercise-induced Ischemia, and the Influence of the Pain Modulating System in a Prolonged NGF Sensitized Muscle.

Conditions
-----------------
Pain Response, Hyperalgesia, Healthy Subjects

Intervention / Treatment
-----------------
* Drug: NGF
* Drug: Isotonic-saline


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGF condition + Control condition<br>All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. | Drug: NGF<br>* Intramuscular injection<br>* Other names: Beta-Nerve Growth Factor, Human;Drug: Isotonic-saline<br>* Intramuscular injection<br>* Other names: Control;|
| Experimental: Control condition + NGF condition<br>All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. | Drug: NGF<br>* Intramuscular injection<br>* Other names: Beta-Nerve Growth Factor, Human;Drug: Isotonic-saline<br>* Intramuscular injection<br>* Other names: Control;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ischemic-induced pain intensity | Subjects perform a repeated static exercise with their dominant leg while a cuff is mounted over the knee to occlude the blodflow from the muscle (ischemia). Subjects subsequently rate their perceived pain intensity verbally on a 11-point numeric rating scale (NRS) rating from 0 (no pain) to 10 (worst pain imaginable). | Assessed right after the exercise has been performed, change from baseline at 3 weeks | 
| Functional muscle pain | Subjects evaluate their muscle pain during movement using a 7-point Likert Scale for lower limp rating from 0 (a complete absence of pain) to 6 (a severe pain that limits my ability to move). | Change from baseline at 3 weeks | 
| Conditioning pain modulation (CPM) efficacy | A test stimuli will be applied and compared with a test stimuli simultaneous a condition stimuli. | Change from baseline at 3 weeks | 
| Temporal summation of pain | 10 repeated stimuli will be applied and subjects will be asked to rate the pain for each individual stimuli on a 11-point visual analogue scale (VAS) rating from 0 (no pain) to 10 (worst pain imaginable) | Change from baseline at 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NGF-induced hyperalgesia, Exercise-induced ischemic pain, Pain modulation, NGF pain model