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.