Developing Brain Stimulation as a Treatment for Chronic Pain in Opiate Dependent
| Status: | Recruiting |
|---|---|
| Conditions: | Back Pain, Back Pain, Chronic Pain, Chronic Pain, Psychiatric, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Musculoskeletal, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 3/2/2019 |
| Start Date: | February 22, 2019 |
| End Date: | July 2021 |
| Contact: | Colleen A Hanlon, PhD |
| Email: | hanlon@musc.edu |
| Phone: | 843-792-5732 |
Effective control of chronic pain is a top priority in the United States, as approximately
10% of adults have severe chronic pain - most of which is chronic lower back pain (CLBP).
However, despite the advances in neuroscience over the past 20 years, chronic pain is still
largely treated with opiate narcotics, much as was done in the Civil War. In addition to the
high abuse liability and dependence potential, only 30-40% of chronic pain patients declare
they receive satisfactory (>50%) relief from their pain through pharmacological treatment. In
these patients a common clinical practice is to escalate the dose of opiates as tolerance
develops - which unfortunately has contributed to escalation in opiate overdose deaths, a
resurgence of intravenous heroin use, and $55 billion in societal costs. Consequently there
is a critical need for new, treatments that can treat pain and reduce reliance on opiates in
individuals with chronic pain.
Aim 1. Evaluate repetitive Transcranial Magnetic Stimulation (rTMS) to the dorsolateral
prefrontal cortex (DLPFC) as a tool to dampen pain and the engagement of the Pain Network.
Hypothesis 1: DLPFC TMS will attenuate the baseline brain response to pain (Pain Network
activity) and increase activity in the Executive Control Network (ECN) when the patient is
given instructions to 'control' the pain.
Aim 2. Evaluate Medial Prefrontal Cortex (MPFC) rTMS as a tool to dampen pain and the
engagement of the Pain Network. Hypothesis 1: MPFC TMS will also attenuate the baseline brain
response to pain (Pain Network activity) but will not effect the ECN or the Salience Network
(SN) when the patient is given instructions to 'control' the pain.
10% of adults have severe chronic pain - most of which is chronic lower back pain (CLBP).
However, despite the advances in neuroscience over the past 20 years, chronic pain is still
largely treated with opiate narcotics, much as was done in the Civil War. In addition to the
high abuse liability and dependence potential, only 30-40% of chronic pain patients declare
they receive satisfactory (>50%) relief from their pain through pharmacological treatment. In
these patients a common clinical practice is to escalate the dose of opiates as tolerance
develops - which unfortunately has contributed to escalation in opiate overdose deaths, a
resurgence of intravenous heroin use, and $55 billion in societal costs. Consequently there
is a critical need for new, treatments that can treat pain and reduce reliance on opiates in
individuals with chronic pain.
Aim 1. Evaluate repetitive Transcranial Magnetic Stimulation (rTMS) to the dorsolateral
prefrontal cortex (DLPFC) as a tool to dampen pain and the engagement of the Pain Network.
Hypothesis 1: DLPFC TMS will attenuate the baseline brain response to pain (Pain Network
activity) and increase activity in the Executive Control Network (ECN) when the patient is
given instructions to 'control' the pain.
Aim 2. Evaluate Medial Prefrontal Cortex (MPFC) rTMS as a tool to dampen pain and the
engagement of the Pain Network. Hypothesis 1: MPFC TMS will also attenuate the baseline brain
response to pain (Pain Network activity) but will not effect the ECN or the Salience Network
(SN) when the patient is given instructions to 'control' the pain.
The goal of this proposal is to evaluate two novel non-invasive brain stimulation strategies
to mitigate pain and the brain's response to pain in CLBP patients. Transcranial Magnetic
Stimulation (TMS), can induce long term potentiation (LTP-like) and long term depression
(LTD-like) effects on brain activity in a frequency dependent manner. The investigators have
previously demonstrated that LTP-like TMS to the dorsolateral prefrontal cortex (DLPFC, a
node in the Executive Control Network (ECN)) can decrease perceived pain and corresponding
Blood Oxygen Level Dependent (BOLD) signal in the "Pain Network'. The Pain Network is an
expansion of the Salience Network (SN; insula, dorsal anterior cingulate) which includes the
thalamus and somatosensory cortex. The analgesic effects of DLPFC TMS can be blocked by
naloxone - suggesting that the analgesic effects of LTP-like DLPFC TMS are opiate mediated.
Additionally, DLPFC TMS delivered postoperatively leads to less patient administered morphine
use (PCA-pump) in the hospital and less opiate use in the outpatient setting. These data all
suggest that LTP-like DLPFC TMS is a promising candidate for treating pain.
An alternative strategy is to apply LTD-like stimulation to the medial prefrontal cortex
(LTD-like mPFC rTMS. This strategy is based on the understanding of functional neural
architecture, wherein the SN is modulated by two other core networks: the ECN and the default
mode network (DMN). As stated above, it is possible to attenuate activity in the SN through
LTP-like TMS to the DLPFC, a node in the ECN. It is also possible to attenuate the SN through
LTD-like TMS to the ventral medial prefrontal cortex (a node in the DMN). The proposed study
will be the first to employ a randomized, double-blind, sham-controlled design to
parametrically evaluate the longitudinal effects of 16 days of rTMS to the DLPFC (Aim 1) or
the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in
a cohort of patients recruited from the community as well as Medical University of South
Carolina clinics with chronic lower back pain that may or may not be using prescription
opiates for 3 or more months without adequate pain relief. Participants will be randomized to
receive rTMS to the DLPFC (10Hz), MPFC (cTBS), or sham (50% at each site), using a Latin
square randomization. Resting state connectivity will be collected along with data from a
standardized thermal pain paradigm wherein individuals are exposed to pain and instructed to
try to "control' the pain. MRI data will be collected 3 times: before the 1st day of TMS,
after the 12th day of TMS, and before the 16th day of TMS (the last day administered).
to mitigate pain and the brain's response to pain in CLBP patients. Transcranial Magnetic
Stimulation (TMS), can induce long term potentiation (LTP-like) and long term depression
(LTD-like) effects on brain activity in a frequency dependent manner. The investigators have
previously demonstrated that LTP-like TMS to the dorsolateral prefrontal cortex (DLPFC, a
node in the Executive Control Network (ECN)) can decrease perceived pain and corresponding
Blood Oxygen Level Dependent (BOLD) signal in the "Pain Network'. The Pain Network is an
expansion of the Salience Network (SN; insula, dorsal anterior cingulate) which includes the
thalamus and somatosensory cortex. The analgesic effects of DLPFC TMS can be blocked by
naloxone - suggesting that the analgesic effects of LTP-like DLPFC TMS are opiate mediated.
Additionally, DLPFC TMS delivered postoperatively leads to less patient administered morphine
use (PCA-pump) in the hospital and less opiate use in the outpatient setting. These data all
suggest that LTP-like DLPFC TMS is a promising candidate for treating pain.
An alternative strategy is to apply LTD-like stimulation to the medial prefrontal cortex
(LTD-like mPFC rTMS. This strategy is based on the understanding of functional neural
architecture, wherein the SN is modulated by two other core networks: the ECN and the default
mode network (DMN). As stated above, it is possible to attenuate activity in the SN through
LTP-like TMS to the DLPFC, a node in the ECN. It is also possible to attenuate the SN through
LTD-like TMS to the ventral medial prefrontal cortex (a node in the DMN). The proposed study
will be the first to employ a randomized, double-blind, sham-controlled design to
parametrically evaluate the longitudinal effects of 16 days of rTMS to the DLPFC (Aim 1) or
the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in
a cohort of patients recruited from the community as well as Medical University of South
Carolina clinics with chronic lower back pain that may or may not be using prescription
opiates for 3 or more months without adequate pain relief. Participants will be randomized to
receive rTMS to the DLPFC (10Hz), MPFC (cTBS), or sham (50% at each site), using a Latin
square randomization. Resting state connectivity will be collected along with data from a
standardized thermal pain paradigm wherein individuals are exposed to pain and instructed to
try to "control' the pain. MRI data will be collected 3 times: before the 1st day of TMS,
after the 12th day of TMS, and before the 16th day of TMS (the last day administered).
Inclusion Criteria:
- Age 18 to 75 (to maximize participation)
- Currently using prescription opiates
- Able to read and understand questionnaires and informed consent.
- Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not
currently prescribed medications known to lower seizure threshold)
- Does not have metal objects in the head/neck.
- Does not have a history of traumatic brain injury, including a head injury that
resulted in hospitalization, loss of consciousness for more than 10 minutes, or having
ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage.
- Does not have a history of claustrophobia leading to significant clinical anxiety
symptoms.
Exclusion Criteria:
- Any psychoactive illicit substance use (except marijuana and nicotine) within the last
30 days by self-report and urine drug screen. For marijuana, no use within the last
seven days by verbal report and negative (or decreasing) urine
Carboxy-Tetrahydrocannabinol levels.
- Meets Diagnostic and Statistical Manual of Mental Disorders IV criteria for current
axis I disorders of major depression, panic disorder, obsessive-compulsive disorder,
post traumatic stress syndrome, bipolar affective disorder, schizophrenia, dissociate
disorders, eating disorders, and any other psychotic disorder or organic mental
disorder.
- Has current suicidal ideation or homicidal ideation.
- Has the need for maintenance or acute treatment with any psychoactive medication
including anti-seizure medications and medications for Attention Deficit Hyperactivity
Disorder.
- Females of childbearing potential who are pregnant (by urine human chorionic
gonadotropin level), nursing, or who are not using a reliable form of birth control.
- Has current charges pending for a violent crime (not including driving under the
influence related offenses).
- Does not have a stable living situation.
- Suffers from chronic migraines.
We found this trial at
1
site
171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Phone: 843-792-5732
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