Effects of Percutaneous Neuromodulation on Plasticity in the Somatosensory System in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
Echography guided percutaneous neuromodulation is a physical therapy technique, whose main objective is the treatment of pain with direct stimulation of the peripheral nerves using a rome needle of acupuncture as an active electrode for applying currents of electrostimulation. The neurophysiological basis and the effects on the sensory and motor systems of this technique are not characterised. The present study proposes to perform the intervention on the area adjacent to the median nerve and to apply different stimulation protocols on healthy subjects to answer those questions.

Detailed Description
-----------------
Intervention is going to be performed in the medial side of the arm, where the median nerve is accessible to the intervention. The theoretical basis of the technique is to produce specific controlled changes in the somatosensory system using synaptic plasticity, to ultimate affect the perception of pain through reduction of nociception afference. Subsequently, the protocols are based on synaptic physiology and the circuitry of the somatosensory system. The protocols are the following: - low-frequency and high-intensity of stimulation: 2hz during 16 min at an slightly annoying intensity, to induce synaptic depression on the c-fibers circuit, presumably carrying nociception. - high-frequency and low-intensity of stimulation: 100 hz in 5 second trains, separated by 1 min of no current with a perceptible but mild intensity, to induce potentiation of a-beta fibers, presumably englobing mechanoreceptors which inhibit nociception through gate control in the spinal cord. - placebo group has got the same intervention, but without current. The study design is an experimental clinical trial, with randomized order of intervention with repeated measurements. This means each subject is having the three protocols at randomized order, with a gap of at least two weeks between them. The study is triple-blinded. Somatomotor system variables, as sensory and pain pressure thresholds, grip strength, surface electromyographic activity and blood flow are evaluated on the hand of the subject. The arm to treat was also randomized for each subject The measurements are pre-intervention, post-intervention and 24 hours after the intervention for each protocol. Blood flow are measured only pre-intervention and post-intervention.

Official Title
-----------------
Effects of Percutaneous Neuromodulation on Plasticity in the Somatosensory System

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Other: Ultrasound guided percutaneous neuromodulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: healthy. more than 18 years old amateur athlete. Exclusion criteria: to suffer or to have suffered any pathology on the arm on the last 30 days. to suffer some disease discouraging current application or needle¡ing, as coagulation deficit, etc. to suffer some disease as diabetes mellitus, cancer, neurology disease, depression, fibromyalgia, etc. to consume drugs as coagulants, anti-depressant, pregabalin, etc during investigation or the first week before investigation. to consume nsaids the last 48 hours before investigation or during investigation. to consume opioids the first week before investigation or during investigation. belonephobia. professional athlete to be pregnant to suffer immunodepression

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized intervention of repeated measures, quadruple-blinded
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-frequency and high-intensity<br>The intervention of ultrasound guided percutaneous neuromodulation is applied over the median nerve. The parameters are continuous stimulation of low frequency (2 hz) and high intensity (slightly painful) during 16 minutes. | Other: Ultrasound guided percutaneous neuromodulation<br>* It is a technique that consists in the electrical stimulation of peripheral nerve trunks, inserting an acupuncture needle in its path and using it as an electrode to apply electrical current<br>|
| Experimental: High-frequency and low-intensity<br>The intervention of ultrasound guided percutaneous neuromodulation is applied over the median nerve. The parameters are high frequency (100 hz) and low intensity trains. There are 5 trains, 5 second active current and 55 second without current per train. The current is off on the first 11 minutes and the next 5 minutes it will be on. The total time is 16 minutes. | Other: Ultrasound guided percutaneous neuromodulation<br>* It is a technique that consists in the electrical stimulation of peripheral nerve trunks, inserting an acupuncture needle in its path and using it as an electrode to apply electrical current<br>|
| Sham Comparator: Control group<br>The intervention of ultrasound guided percutaneous neuromodulation is applied over the median nerve without current during 16 minutes. | Other: Ultrasound guided percutaneous neuromodulation<br>* It is a technique that consists in the electrical stimulation of peripheral nerve trunks, inserting an acupuncture needle in its path and using it as an electrode to apply electrical current<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical Threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of mechanical sensation, that caliber is considered the pressure threshold to elicit mechanical. The test is performed with subject's eyes closed | Pre-intervention / baseline | 
| Mechanical Threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of mechanical sensation, that caliber is considered the pressure threshold to elicit mechanical. The test is performed with subject's eyes closed. | Immediately after the intervention | 
| Mechanical Threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of mechanical sensation, that caliber is considered the pressure threshold to elicit mechanical. The test is performed with subject's eyes closed. | 24 hours after the intervention | 
| Pinprick pain threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of pinprick sensation, that caliber is considered the pressure threshold to elicit pinprick pain. The test is performed with subject's eyes closed | pre-intervention / baseline | 
| Pinprick pain threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of pinprick sensation, that caliber is considered the pressure threshold to elicit pinprick pain. The test is performed with subject's eyes closed | Immediately after the intervention | 
| Pinprick pain threshold elicited with Von Frey Filaments | We use Von Frey Filaments of increasing caliber to make pression in the evaluated areas. When the test subject reports perception of pinprick sensation, that caliber is considered the pressure threshold to elicit pinprick pain. The test is performed with subject's eyes closed | 24 hours after the intervention | 
| Pain evocated with Von Frey Filaments. | We use Von Frey Filaments of increasing caliber to make pression with 100g, 180g and 300g in the evaluated areas. Each filament to make pression three times. The subject reports the pain in a scale of 0-10 number (scale NSR: 0 is any pain and 10 is the maximal perception of pain. The test is performed with subject's eyes closed. | Pre-intervention / baseline | 
| Pain evocated with Von Frey Filaments. | We use Von Frey Filaments of increasing caliber to make pression with 100g, 180g and 300g in the evaluated areas. Each filament to make pression three times. The subject reports the pain in a scale of 0-10 number (scale NSR: 0 is any pain and 10 is the maximal perception of pain. The test is performed with subject's eyes closed. | Immediately after the intervention | 
| Pain evocated with Von Frey Filaments. | We use Von Frey Filaments of increasing caliber to make pression with 100g, 180g and 300g in the evaluated areas. Each filament to make pression three times. The subject reports the pain in a scale of 0-10 number (scale NSR: 0 is any pain and 10 is the maximal perception of pain. The test is performed with subject's eyes closed. | 24 hours after the intervention | 
| Pressure pain threshold with algometer. | On the marked areas we make pressure with pressure algometer. When the subject experiences any sense of pain, he/she has to say stop and immediately the algometer was removed. The number in Kg marked by the algometer is annotated. The mean of two measurements was taken for analysis. The second measurement was taken with a minimum of 30 seconds after the previous one. | pre-intervention / baseline | 
| Change in pressure pain threshold with algometer. | On the marked areas we make pressure with pressure algometer. When the subject experiences any sense of pain, he/she has to say stop and immediately the algometer was removed. The number in Kg marked by the algometer is annotated. The mean of two measurements was taken for analysis. The second measurement was taken with a minimum of 30 seconds after the previous one. | Immediately after the intervention | 
| Change in pressure pain threshold with algometer. | On the marked areas we make pressure with pressure algometer. When the subject experiences any sense of pain, he/she has to say stop and immediately the algometer was removed. The number in Kg marked by the algometer is annotated. The mean of two measurements was taken for analysis. The second measurement was taken with a minimum of 30 seconds after the previous one. | 24 hours after the intervention | 
| Maximum grip force with dynamometer | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | pre-intervention / baseline | 
| Change in maximum grip force with dynamometer | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | Immediately after the intervention | 
| Change in maximum grip force with dynamometer. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | 24 hours after the intervention | 
| Maximum grip force with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | pre-intervention / baseline | 
| Change in maximum grip force with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | Immediately after the intervention | 
| Change in maximum grip force with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during 5 second, 3 times with 30 seconds to rest between them. | 24 hours after the intervention | 
| Arterial peak systolic velocity with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial peak systolic during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial peak systolic velocity with Color Doppler Ultrasonography in placebo group | In placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial peak systolic during 5 cardiac cycles inmediately after introduce the needly in the arm. | Immediately after the needle insertion | 
| Change in arterial peak systolic velocity with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial peak systolic during 5 cardiac cycles. | Immediately after the intervention | 
| Arterial volume flow with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial volume flow during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial volume flow with Color Doppler Ultrasonography | In placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial volume flow during 5 cardiac cycles. | Immediately after the needle insertion | 
| Change in arterial volume flow with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial volume flow during 5 cardiac cycles. | Immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electric current threshold of perception with low frequency | Using the intervention needle as an active electrode. The parameters are 2 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | pre-intervention / baseline | 
| Change in Electric current threshold of perception with low frequency | Using the intervention needle as an active electrode. The parameters are 2 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | Immediately after the intervention | 
| Change in Electric current threshold of perception with low frequency | Using the intervention needle as an active electrode. The parameters are 2 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | 24 hours after the intervention | 
| Electric current threshold of perception with high frequency | Using the intervention needle as an active electrode. The parameters are 100 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | pre-intervention / baseline | 
| Change electric current threshold of perception with high frequency | Using the intervention needle as an active electrode. The parameters are 100 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | Immediately after the intervention | 
| Change electric current threshold of perception with high frequency | Using the intervention needle as an active electrode. The parameters are 100 hz and 150 msec of pulse duration and the intensity was increased progressively. When the subject experienced any sense of pain, sensitivity and muscle contraction in the needle and arm, he/she must tell it and the threshold is annotated. | 24 hours after the intervention | 
| Force grip resistance with dynamometer | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | Pre-intervention / Baseline | 
| Change in Force grip resistance with dynamometer. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | Immediately after the intervention | 
| Change in Force grip resistance with dynamometer. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | 24 hours after the intervention | 
| Force grip resistance with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | Pre-intervention / Baseline | 
| Change in Force grip resistance with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | Immediately after the intervention | 
| Change in Force grip resistance with surface electromyography. | The subject is standing with the dynamometer in his hand. He/she must press the dynamometer during one minute trying to maintain maximal force. | 24 hours after the intervention | 
| Neural tension test (ROM) | The subject is lying on the stretcher. We make a neurodynamic test and when she/he experience tension in his/her arm, she/he must tell us stop. We measure the range of motion of the elbow extension as the outcome | pre-intervention / baseline | 
| Change in neural tension test (ROM) | The subject is lying on the stretcher. We make a neurodynamic test and when she/he experience tension in his/her arm, she/he must tell us stop. We measure the range of motion of the elbow extension as the outcome | Immediately after the intervention | 
| Change in neural tension test (ROM) | The subject is lying on the stretcher. We make a neurodynamic test and when she/he experience tension in his/her arm, she/he must tell us stop. We measure the range of motion of the elbow extension as the outcome | 24 hours after the intervention | 
| Change in arterial end-diastolic velocity with Color Doppler Ultrasonography | In the placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial end-diastolic velocity during 5 cardiac cycles. | Immediately after the needle insertion | 
| Arterial time average mean velocity during cardiac cycle with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average mean velocity during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial time average mean velocity during cardiac cycle with Color Doppler Ultrasonography | In the placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average mean velocity during 5 cardiac cycles. | Immediately after the needle insertion | 
| Arterial end-diastolic velocity with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial end-diastolic velocity during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial end-diastolic velocity with Color Doppler Ultrasonography | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial end-diastolic velocity during 5 cardiac cycles. | Immediately after the intervention | 
| Change in arterial time average mean velocity during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average mean velocity during 5 cardiac cycles. | Immediately after the intervention | 
| Arterial time average maximun velocity during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average maximun velocity during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial time average maximun velocity during cardiac cycle with Color Doppler | In placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average maximun velocity during 5 cardiac cycles. | Immediately after the needle insertion | 
| Change in arterial time average maximun velocity during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial time average maximun velocity during 5 cardiac cycles. | Immediately after the intervention | 
| Arterial pulsatility index during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial pulsatility index during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial pulsatility index during cardiac cycle with Color Doppler | In placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial pulsatility index during 5 cardiac cycles. | Immediately after the needle insertion | 
| Change in arterial pulsatility index during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial pulsatility index during 5 cardiac cycles. | Immediately after the intervention | 
| Arterial arterial resistivity index during cardiac cycle with Color Doppler | In placebo group, on the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial resistivity index during 5 cardiac cycles. | pre-intervention / baseline | 
| Change in arterial resistivity index during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial resistivity index during 5 cardiac cycles. | Immediately after the needle insertion | 
| Change in arterial resistivity index during cardiac cycle with Color Doppler | On the marked areas (Brachial ipsilateral and contralateral, radial and ulnar arteries) we measure the arterial resistivity index during 5 cardiac cycles. | Immediately after the intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Plasticity, Echography guided percutaneous neuromodulation, somatomotor system, Peripheral nerve stimulation, Pain