4.4.2 Functional Magnetic Resonance Imaging
Functional magnetic resonance imaging (fMRI) captures changes in blood
flow (as a proxy for brain activity) within the brain during a variety
of states to provide insight into how the brain responds to certain
stimuli and tasks158; it has also been used as a proxy
of neural correlates of pain in the human brain159.
Multiple studies have found that painful stimulation activates regions
involved in the so-called “pain matrix” of the brain, including the
primary and secondary somatosensory cortices, anterior cingulate cortex
(ACC), and insula160, 161. Similarly, fMRI studies
reveal not only alterations in brain activity associated with pain
states but also specific abnormalities in regions related to reward and
emotion regulation — such as the thalamus, striatum, and
prefrontal162, 163.
Focusing specifically on persons with OUD, a prospective, non-blinded,
single-arm pilot study by Faraj and colleagues aimed to examine the
effects of a 12-week virtual reality (VR) meditative intervention on
chronic pain in 15 patients with OUD receiving
methadone164. The VR-based intervention incorporated
therapist-guided martial arts movements, breathing techniques, and
meditation exercises using narration and VR technology. Patients
completed 30-minute biweekly sessions that taught relaxation through
coordinated upper body movements and breathing. During fMRI scans,
patients first had a 10-minute resting state scan with their eyes
closed. They then watched a 5-minute video designed to evoke mental
states related to physical pain, as well as control, social, and
mentalizing conditions. Before and after each biweekly intervention
session, patients also rated their baseline chronic pain (BPI) and
opioid craving on a 0-10 VAS. Results showed VAS ratings of pain, opioid
craving, anxiety, and depression decreased significantly after each
session compared to pre-session. The fMRI showed that after the 12-week
meditation intervention, patients showed reduced activity in the
postcentral gyrus, a region involved in processing physical pain
sensations, when watching the two video tasks and also exhibited reduced
postcentral gyrus connectivity with some other key pain neuromatrix
regions, like the anterior cingulate cortex. This provides evidence for
the usefulness of the fMRI in assessing the pain neuromatrix activation
in individuals with OUD.
In an adjacent population, an experimental pilot study conducted by
Dowdle and colleagues evaluated the pattern and amplitude of neural
activity associated with acute pain in patients with chronic
non-alcoholic pancreatitis who had been using prescription opioids daily
for at least six months, compared to gender-matched non-opioid using
healthy controls165. Twenty-eight participants
underwent fMRI and completed the BPI and Current Opioid Misuse Measure
to assess pain and opioid misuse. An individualized painful thermal
stimulus equivalent to a pain rating of 7/10 was determined using a
thermode on capsaicin-sensitized skin. During functional MRI scanning,
participants underwent 3 runs of 14-second blocks of the personalized
painful thermal stimulus alternating with 19-second blocks of a
non-painful 32°C stimulus. Relative to controls, the patient group
reported significantly higher pain scores on the BPI and showed
significantly greater activity during acute pain in somatosensory
cortex, anterior cingulate cortex, and occipital regions. The amplitude
of ACC response correlated positively with opioid dose. In summary, this
fMRI study demonstrated that compared to healthy controls, patients with
chronic pain using prescription opioids have an amplified neural
response to acute experimental pain, likely related to hyperalgesia,
particularly in pain processing regions like somatosensory and cingulate
cortex. Despite not studying people with OUD, as chronic prescription
opioid use is different than the disorder, the authors suggest that the
fMRI technique helped identify targets for future targeted-treatments
pain among people with chronic opioid usage, including OUD.
As demonstrated in this section, few studies have used fMRI studies in
patients with OUD have assessed pain as an outcome. Despite that, fMRI
has the potential to elucidate brain dysfunction for OUD patients,
allowing for a better understanding of their symptoms and experiences,
which allows for the future development of treatments that target these
symptoms and help maintain remission from opioids. It is important to
note that fMRI may be particularly helpful for the measurement of
pain-correlates, but not of pain experience itself, which is
fundamentally subjective. It is limited in its ability to provide
clinically relevant results for the understanding and treatment of OUD
in its current state. Development of improved imaging techniques in the
future is required to make substantial conclusions on pain and OUD
treatment.