Neuromodulation of Lidocaine and Capsaicin Cream Effects on Pain Experience

Neuromodulation of Placebo and Nocebo Effects

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Device: transcranial direct current stimulation (tDCS); Other: Lidocaine cream; Other: Capsaicin cream; Other: Control cream

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: tDCS Enhancement; 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); 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.; Other: Lidocaine cream; Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).; Other: Capsaicin cream; Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).; Other: Control cream; A neutral cream will be applied on the arm as a control.
EXPERIMENTAL: tDCS Inhibition; 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); 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.; Other: Lidocaine cream; Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).; Other: Capsaicin cream; Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).; Other: Control cream; A neutral cream will be applied on the arm as a control.
SHAM_COMPARATOR: Sham tDCS; 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); 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.; Other: Lidocaine cream; Lidocaine cream will be applied on the arm to reduce pain sensitivity (analgesia).; Other: Capsaicin cream; Capsaicin cream will be applied on the arm to increase pain sensitivity (hyperalgesia).; Other: Control cream; A neutral cream will be applied on the arm as a control.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2016
• Primary Completion (ACTUAL): March 1, 2019
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (ACTUAL): April 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: June 19, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Dermatologic Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antipruritics; Lidocaine; Capsaicin
• Other Study ID Numbers: 2015P000685

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO