January 6, 2014

Functional MRI (fMRI) proved useful for identifying early signals of treatment efficacy in patients with chronic pain, according to researchers.

In a placebo-controlled, crossover study done in 19 patients with hand osteoarthritis (OA), fMRI was able to detect changes in signals in brain regions associated with in pain in response to naproxen sodium, reported Matthew Howard, PhD, of King’s College in London, and colleagues.

They found that reductions in blood-oxygen-level dependent (BOLD) signals “were identified in brain regions commonly associated with the experience of being in pain, several of which we hypothesized a priori to show changes in response to analgesia,” they wrote in Arthritis and Rheumatology.

To fully understand the neural mechanisms of drug action, “fMRI must depict the neural correlates of the analgesic response in patients experiencing persistent pain,” the authors explained. Preliminary fMRI studies in OA were underpowered or lacked placebo control to establish neural correlates of analgesic response.

Their crossover study involved patients with a confirmed diagnosis of right-handed, first carpometacarpal joint OA, according to American College of Rheumatology criteria. All were right-hand dominant and had a background pain intensity score ≥4 on an 11-point numeric rating scale (NRS) at screening.

Patients underwent fMRI scanning sessions following a 1-week regimen of naproxen or placebo, with the intent to detect naproxen-induced changes in brain activity using a functionally relevant task that evoked pain. This task consisted of squeezing a key-shaped pressure device using the affected hand (lateral pinch) to mimic gripping or handling of objects. Participants also kept a diary in which they recorded perceived pain intensity using the NRS. The final analysis set included 19 patients.

Compared with placebo, naproxen reduced pain intensity on the NRS at day seven by 3.2 points (P=0.005). Scores on a visual analog scale (VAS) of pain, the Present Pain Intensity, and the sensory subsection of the Short Form-McGill Pain Questionnaire were also significantly lower after naproxen administration compared with placebo (P<0.001,P=0.004, and P=0.004, respectively). Wrist and hand pain and function were significantly better following naproxen compared with placebo (P=0.05).

When measured in the MRI scanner, the squeezing task performed at 10%, 40%, and 70% of maximum voluntary contraction (MVC) induced a significant increase in VAS scores (P<.0001). Task performance at 70% MVC evoked the highest perceived pain intensity scores.

In analyzing brain regions involved with pain perception as identified from task performance, the authors discovered significant naproxen-mediated reductions in BOLD signal intensity in the amygdala, hippocampal formation, thalamus, primary somatosensory and posterior cingulate cortex bilaterally.

“Given the location of reductions in BOLD response following naproxen and the relationship in thalamus, primary and secondary somatosensory cortices between changes in BOLD signal intensity and perceived pain, we infer that our fMRI findings represent an analgesic effect of naproxen on OA-related evoked pain,” the authors wrote. “These findings demonstrate that BOLD fMRI adds value to conventional self-report measures, offering a mechanistic understanding of both pain and treatment response.”

Study limitations included the small sample size. The authors also acknowledged that ascertaining treatment effect from single regions of interest in the brain in isolation may be overly simplistic, but they added that “pain is a multifaceted experience underpinned by a complex network of brain regions … a critical quality provided by the use of neuroimaging endpoints is the value they add to conventional behavioral indices, providing mechanistic correlates of persistent pain and treatment effects.”


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