Neuromodulation of Lidocaine and Capsaicin Cream Effects on Pain Experience

Study Overview
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Brief Summary
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The aim of this study is to use a brain stimulation tool called transcranial direct current stimulation (tDCS) to investigate the analgesic (reducing sensitivity to pain) effects of lidocaine cream and the hyperalgesic (increasing sensitivity to pain) effects of capsaicin cream using a neutral cream as a control. tDCS stimulation has been shown to temporarily influence the way the stimulated part of the brain functions. With this method, the involvement of specific parts of the brain can be investigated in the working of the brain as a whole.

Official Title
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Neuromodulation of Placebo and Nocebo Effects

Conditions
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Pain

Intervention / Treatment
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* Device: transcranial direct current stimulation (tDCS)
* Other: Lidocaine cream
* Other: Capsaicin cream
* Other: Control cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right handed healthy male and female adults aged 21-50 No contraindications to fMRI scanning At least a 10th grade English-reading level; English can be a second language provided that the patients feel they understand all the questions used in the assessment measures. Exclusion Criteria: Current or past history of major medical, neurological, or psychiatric illness Claustrophobia History of head trauma Instability of responses to experimental pain Non-fluent speaker of English Presence of any contraindications to fMRI scanning. For example: cardiac pacemaker, metal implants, fear of closed spaces, pregnancy History of alcohol/substance abuse

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tDCS Enhancement<br>In this group, the transcranial direct current stimulation (tDCS) stimulates the areas of the brain being examined in this study to increase their activity. | Device: transcranial direct current stimulation (tDCS)<br>* tCDS safely applies a weak electrical current to your scalp using two sponge electrodes that look like flat circular pads. The pads will be held in place on your head with a neoprene cap. The pads will be attached to a generator that will send a weak stimulus to your scalp. This current influences the way that your brain cells work. When the stimulus starts, you might feel a tingling sensation underneath the electrode pads. That sensation is not painful and goes away in seconds.<br>Other: Lidocaine cream<br>* Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).<br>Other: Capsaicin cream<br>* Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).<br>Other: Control cream<br>* A neutral cream will be applied on the arm as a control.<br>|
| Experimental: tDCS Inhibition<br>In this group, the transcranial direct current stimulation (tDCS) inhibits the areas of the brain being examined in this study to decrease their activity. | Device: transcranial direct current stimulation (tDCS)<br>* tCDS safely applies a weak electrical current to your scalp using two sponge electrodes that look like flat circular pads. The pads will be held in place on your head with a neoprene cap. The pads will be attached to a generator that will send a weak stimulus to your scalp. This current influences the way that your brain cells work. When the stimulus starts, you might feel a tingling sensation underneath the electrode pads. That sensation is not painful and goes away in seconds.<br>Other: Lidocaine cream<br>* Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).<br>Other: Capsaicin cream<br>* Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).<br>Other: Control cream<br>* A neutral cream will be applied on the arm as a control.<br>|
| Sham Comparator: Sham tDCS<br>Sham transcranial direct current stimulation (tDCS) does not provide real stimulation though you will not know this until your debriefing at the end of the study. Sham will be used to determine if the results of this study are due to the tDCS or other reasons. | Device: transcranial direct current stimulation (tDCS)<br>* tCDS safely applies a weak electrical current to your scalp using two sponge electrodes that look like flat circular pads. The pads will be held in place on your head with a neoprene cap. The pads will be attached to a generator that will send a weak stimulus to your scalp. This current influences the way that your brain cells work. When the stimulus starts, you might feel a tingling sensation underneath the electrode pads. That sensation is not painful and goes away in seconds.<br>Other: Lidocaine cream<br>* Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).<br>Other: Capsaicin cream<br>* Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).<br>Other: Control cream<br>* A neutral cream will be applied on the arm as a control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Functional Connectivity Changes of the DLPFC Before and After tDCS Stimulation | We investigated the effects of cathodal (inhibition) and anodal (enhancement) tDCS on rDLPFC functional connectivity (FC) with the supplementary motor area (SMA) and anterior insula. Higher Fisher Z-scores represent greater resting-state functional connectivity. | up to 2 weeks | 
| fMRI Resting States Functional Connectivity Changes During Pain Stimulation | We measured changes in blood oxygen level-dependent (BOLD) activity in the brain during pain stimulation. In the outcome measure data table, placebo contrast indicates lidocaine - neutral and nocebo contrast indicates capsaicin - neutral. | up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gracely Sensory Scale Pain Rating Changes in Response to Lidocaine and Capsaicin Creams and tDCS | The Gracely Sensory Scale allows participants to rate the intensity of heat pain stimuli on a scale from 0 to 20, with 0 indicating no pain sensation and 20 indicating extremely intense pain. The outcome measure data table shows mean pain ratings for the lidocaine, capsaicin, and neutral creams after enhancement, inhibition, or sham tDCS stimulation. | up to 2 weeks |