Participants will work with the provider to decide which method of treatment they prefer
and will then be followed regularly using standardized pain scores over the next year.
Those undergoing ST will undergo 5-10 sessions while those treated with medical therapy
will undergo titration of medication as per typical standard of care. The investigators
will compare both maximal pain relief achieved and duration achieved between groups.
prospectively enroll a consecutive series of patients presenting to clinic with
post-stroke pain syndromes following either an ischemic infarct or intracranial
hemorrhage. Patients will be included in the study if they are at least one month
post-stroke (but can be chronic) and have pain in an area attributable to the location of
their lesion (ie contralateral to a lesion involving the thalamus or sensory cortex). At
their clinic visit, potential treatments: Scrambler Therapy or pharmacological treatment,
will be discussed with each patient. Patients will not be excluded if they are currently
taking or have taken pain medications in the past, though these variables will be
factored into the analysis. Through shared decision making, the investigator along with
the patients input will decide on ST versus medical management. Participants will consent
to being followed for pain control over the following year of therapy to enable
comparison of ST to standard medical therapy.
All patients will begin by rating their current pain on the Numerical Rating Scale (NRS)
from 0-10.
Patients undergoing treatment by Scrambler Therapy will begin by describing the areas and
levels of pain along the Numerical Rating Scale (NRS) from 0-10. The dermatomes of the
areas of pain will be examined by going up and down the dermatome as shown on a dermatome
map, and the electrode of the Scrambler machine will be placed at the site where pain is
initiated and approximately 10 centimeters above it. The Scrambler machine will then be
started and turned on until patients feel a "tingling" sensation that is not painful. For
approximately 45 minutes, the Scrambler machine will run while a team member watches over
the patient, adjusting the levels only if the patient no longer feels the tingling
sensation.
After the Scrambler treatment, patients will again be asked to describe the areas and
levels of pain using the NRS. Each patient undergoing Scrambler Therapy will undergo this
process for 5 consecutive days, following the same procedure every day of treatment.
After completion of treatment, participants will be asked to complete monthly ratings of
their pain for three months, and to follow-up in clinic at 3-6 month intervals (standard
of care).
While the mechanism of action of ST in treating CNS pain is unknown, thalamocortical
dysrhythmia (TD) is one mechanism hypothesized to underlie post-stroke pain that may be
affected by the neuromodulation. The thalamus serves as a connection hub between cortical
sensory regions and areas of pain perception. Prior work suggests that with TD there is
increased low frequency (beta and theta) bursting within dorsal anterior cingulate cortex
(dACC) and abnormalities within the default mode, central executive, and salience
networks. These abnormalities are observed in patients with chronic pain. We hypothesize
the same is true for post-stroke pain and that ST modulates the aberrant thalamocortical
signaling, reducing maladaptive beta-band activity within the dACC for patients with
significant reductions in pain after treatment. In this proposal, we will build upon our
established infrastructure to collect neuroimaging data from 100 patients who experience
post-stroke pain, each undergoing 5 sessions of ST. Pain scores will be recorded at
baseline and before and after each session. Magnetoencephalography (MEG) will be
performed at baseline, and post- treatments #1 and #5 to investigate for signs of
thalamocortical dysrhythmia by comparing neural responses from this cohort to those of a
similar, previously-collected cohort with no post-stroke pain. We will then determine the
changes in neural activity associated with favorable treatment response (>50% reduction
in pain score at visit #5) among treated individuals, and evaluate whether neural changes
following visit #1 combined with baseline variables are sufficient to predict overall
treatment response. The proposal is built around the following specific aims:
Aim 1: Investigate the role of TD in post-stroke pain by evaluating neuroimaging features
present in symptomatic patients compared to controls. Spectral and functional
connectivity analyses will be performed to evaluate whole brain differences at baseline
between groups with specific focus on 1) low frequency activity within the dACC and 2)
differences within the default mode, central executive, and salience networks.
Hypothesis 1: Affected patients will show high levels of beta activity within the dACC
compared to controls without pain supporting thalamocortical dysrhythmia as an underlying
mechanism.
Aim 2: Determine the neuroimaging patterns associated with favorable treatment response
in patients treated with ST. Similar analyses will also be performed at each time point
(baseline, post-#1, -#5) to evaluate differences between patients treated with ST who
show significant response to treatment versus non-responders.
Hypothesis 2: 1) High levels of beta activity will be present within the dACC at baseline
for all patients, but resolve in patients with >50% reduction in pain scores post-visit
#5, and 2) patients with the highest baseline levels of beta activity within the dACC
will see the greatest absolute decrease in pain scores over time.
Aim 3: Create a multivariable predictive model to guide future treatment. Differences in
neural activity observed post-visit #1 for responders versus non-responders, along with
demographic information, stroke characteristics, and additional treatment variables will
be used in regression analyses to create a multivariable model of factors associated with
favorable treatment response in a training cohort. ROC analysis will be used to determine
the sensitivity and specificity of the model, which will be internally validated for in a
smaller test cohort.
Hypothesis 3: 1) Patients with the greatest decrease in beta activity as a result of
treatment #1 will see the greatest absolute reduction in pain post-visit #5. 2) Strokes
involving either of the bilateral thalami will be less likely to result in >50% reduction
in pain independent of treatment duration, and concurrent use of medications (SNRIs,
TCAs, or antiepileptics) will improve the efficacy of ST.
Using MEG to better understand the underlying neural mechanisms responsible for
post-stroke pain and treatment response will allow us to better predict response to
therapy and individualize treatment paradigms in future clinical trials based on
biomarkers to maximize response, leading to decreased post-stroke morbidity.
