Chronic Pain
Conditions
Keywords
Pain
Brief summary
Although transcranial magnetic stimulation (TMS) is now considered a minimal risk intervention, is approved for the treatment of depression, and is widely used around the world, little is known about mechanisms of action of prefrontal rTMS for depression or pain. There is some evidence that the prefrontal cortex is involved in perception of control and may moderate the effects of perceived controllability on emotional reactivity to painful stimuli. The present study aims to investigate the effects of prefrontal rTMS and perceived controllability on pain perception in healthy adults.
Detailed description
Transcranial magnetic stimulation (TMS) is a minimally invasive brain stimulation technology that can focally stimulate the brain of an awake individual.1,2 A localized pulsed magnetic field transmitted through a figure-8 coil (lasting only microseconds) is able to focally stimulate the cortex by depolarizing superficial neurons3,4 which induces electrical currents in the brain.5 If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS). rTMS over the prefrontal cortex has been shown to produce temporary analgesic effects in healthy adults using laboratory pain methods and in patients with chronic pain of various etiologies. However, little is known about mechanisms of action. Evidence from functional MRI studies suggests that participants' perceived controllability over pain stimuli is associated with decreased pain experience and decreased activation of cortical and subcortical areas involved with pain perception.6 Perceived controllability may involved prefrontal cortical circuits and may be involved in inhibition of limbic system responses to painful stimuli. To date, no studies have investigated the interaction between prefrontal TMS and perceived controllability on pain perception in healthy adults. Building on extensive pilot work and experience in the area of laboratory pain assessment and TMS in the Brain Stimulation Laboratory at MUSC, the investigators propose to investigate the effects of perceived controllability and prefrontal TMS on pain perception in healthy adults. This study may help determine whether TMS can be used to stimulate a cortical area thought to be involved in perceived controllability, thus enhancing one's sense of controllability and thereby substantially reduce pain intensity and unpleasantness. Although transcranial magnetic stimulation (TMS) is now considered a minimal risk intervention, is approved for the treatment of depression, and is widely used around the world, little is known about mechanisms of action of prefrontal rTMS for depression or pain. There is some evidence that the prefrontal cortex is involved in perception of control and may moderate the effects of perceived controllability on emotional reactivity to painful stimuli. The present study aims to investigate the effects of prefrontal rTMS and perceived controllability on pain perception in healthy adults.
Interventions
DEVICEOperator Role Real TMS
In two of the four visits, the participant will be assigned to the operator condition receiving Real TMS. The participant will be assigned a partner and both participants will participate in a numeric-combination-guessing task. Performance on this task will be directly related to the painfulness of a series of thermal stimuli that participants receive. The operator's performance will control the painfulness delivered to both participants. Each participant will play each role twice.
DEVICEReceiver Role Real TMS
In two of the four visits, the participant will be assigned to the receiver condition receiving Real TMS. The participant will be assigned a partner and both participants will participate in a numeric-combination-guessing task. Performance on this task will be directly related to the painfulness of a series of thermal stimuli that participants receive. The receiver's performance on the task will be unrelated to his/her stimulus painfulness. Each participant will play each role twice.
DEVICEOperator Role Sham TMS
In two of the four visits, the participant will be assigned to the operator condition receiving Sham TMS. The participant will be assigned a partner and both participants will participate in a numeric-combination-guessing task. Performance on this task will be directly related to the painfulness of a series of thermal stimuli that participants receive. The operator's performance will control the painfulness delivered to both participants. Each participant will play each role twice.
DEVICEReceiver Role Sham TMS
In two of the four visits, the participant will be assigned to the receiver condition receiving Sham TMS. The participant will be assigned a partner and both participants will participate in a numeric-combination-guessing task. Performance on this task will be directly related to the painfulness of a series of thermal stimuli that participants receive. The receiver's performance on the task will be unrelated to his/her stimulus painfulness. Each participant will play each role twice.
DEVICEAll Participants Operator Role
All participants in Operator Role (Receiving real or sham TMS)
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-75 years of age
Exclusion criteria
* history of seizures or epilepsy * family history of seizures * history of chronic pain conditions * current depression * anxiety disorders * taking any medications shown to lower seizure threshold * metal implants above the waist * pregnant * brain tumors or lesions * pacemaker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Unpleasantness During Perceived Control Condition | 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS | The perceived control condtion of the pain task consisted of 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS). The entire pain task (perceived control condition and no control condition) consisted of 60 trials. Participants in the operator role group rated the unpleasantness of each thermal stimulus on a computerized visual analog scale (VAS). Unpleasantness ratings are on a scale of 0 to 100. 0=not unpleasant. 100=extremely unpleasant. The ratings were averaged over all trials for the perceived control condition for the Real TMS and Sham TMS group. The results below, report the mean unpleasantness rating for both groups during the perceived control condition. |
| Pain Intensity During Perceived Control Condition | 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS | The perceived control condtion of the pain task consisted of 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS). The entire pain task (perceived control condition and no control condition) consisted of 60 trials.), participants in the operator role group rated the pain intensity of each thermal stimulus on a computerized visual analog scale (VAS). Pain intensity ratings are on a scale of 0 to 100. 0=not painful. 100=extremely painful. The ratings were averaged over all trials for the perceived control condition for the Real TMS and Sham TMS group. The results below, report the mean pain intensity rating for both groups during the perceived control condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Correctly Guessed Their TMS Condition Assignment | After Pain Control Paradigm | After each participant completed the experiment, they guessed their TMS Condition, whether they received real or sham TMS. Results below report the number of participants in each group that guessed their TMS condition correctly. |
| Confidence Ratings of Guessing TMS Condition Assignment | After Pain Control Paradigm | After participants guessed their TMS condition; whether they received real or sham TMS, They were then asked to rate the confidence in their guess. Ratings were on a scale of 0-10 where 0=complete guess and 10=absolutely sure. Results below include the mean confidence ratings of those that guessed the TMS condition correctly and those that guessed incorrectly. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Real TMS Participants in the real Transcranial Magnetic Stimulation (TMS) group will receive real stimulation across all interventions; the operator role and the receiver role. rTMS will be used to stimulate the left prefrontal cortex using two Neuronetics TMS machines with figure-8, iron core coils at 10Hz and at 110% of resting motor threshold \[5 second trains following each trial (25 trials per visit)\]. | 12 |
| Sham TMS Participants in the sham Transcranial Magnetic Stimulation (TMS) group will receive sham stimulation across all interventions; the operator role and the receiver role. Sham Stimulation involves 5 second trains of 10Hz rTMS in pairs alternating between real TMS and eSham TMS (randomly ordered). All sham treatment will be delivered with a specially designed, manufacture-provided sham TMS coil that looks and sounds identical to a real TMS coil but no magnetic current is transferred to the participant. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | failed to experience pain at level 7/10 | 2 | 2 |
Baseline characteristics
| Characteristic | Real TMS | Sham TMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Region of Enrollment United States | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pain Intensity During Perceived Control Condition
The perceived control condtion of the pain task consisted of 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS). The entire pain task (perceived control condition and no control condition) consisted of 60 trials.), participants in the operator role group rated the pain intensity of each thermal stimulus on a computerized visual analog scale (VAS). Pain intensity ratings are on a scale of 0 to 100. 0=not painful. 100=extremely painful. The ratings were averaged over all trials for the perceived control condition for the Real TMS and Sham TMS group. The results below, report the mean pain intensity rating for both groups during the perceived control condition.
Time frame: 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Real TMS | Pain Intensity During Perceived Control Condition | 51.5 units on a scale |
| Sham TMS | Pain Intensity During Perceived Control Condition | 57.5 units on a scale |
Primary
Pain Unpleasantness During Perceived Control Condition
The perceived control condtion of the pain task consisted of 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS). The entire pain task (perceived control condition and no control condition) consisted of 60 trials. Participants in the operator role group rated the unpleasantness of each thermal stimulus on a computerized visual analog scale (VAS). Unpleasantness ratings are on a scale of 0 to 100. 0=not unpleasant. 100=extremely unpleasant. The ratings were averaged over all trials for the perceived control condition for the Real TMS and Sham TMS group. The results below, report the mean unpleasantness rating for both groups during the perceived control condition.
Time frame: 30 trials of 1 to 4 seconds of thermal stimulus accompanied by 5 seconds of real or sham TMS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Real TMS | Pain Unpleasantness During Perceived Control Condition | 54.5 units on a scale |
| Sham TMS | Pain Unpleasantness During Perceived Control Condition | 60.5 units on a scale |
Secondary
Confidence Ratings of Guessing TMS Condition Assignment
After participants guessed their TMS condition; whether they received real or sham TMS, They were then asked to rate the confidence in their guess. Ratings were on a scale of 0-10 where 0=complete guess and 10=absolutely sure. Results below include the mean confidence ratings of those that guessed the TMS condition correctly and those that guessed incorrectly.
Time frame: After Pain Control Paradigm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real TMS | Confidence Ratings of Guessing TMS Condition Assignment | 5.07 units on a scale | Standard Deviation 3.56 |
| Sham TMS | Confidence Ratings of Guessing TMS Condition Assignment | 5.70 units on a scale | Standard Deviation 2.83 |
Secondary
Number of Participants That Correctly Guessed Their TMS Condition Assignment
After each participant completed the experiment, they guessed their TMS Condition, whether they received real or sham TMS. Results below report the number of participants in each group that guessed their TMS condition correctly.
Time frame: After Pain Control Paradigm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Real TMS | Number of Participants That Correctly Guessed Their TMS Condition Assignment | 9 Participants |
| Sham TMS | Number of Participants That Correctly Guessed Their TMS Condition Assignment | 5 Participants |
p-value: 0.05Chi-squared