Study unravels how neural circuits that modulate pain sensitivity differ for differentiated metastatic tumors

Two neuropsychological paradigms are proposed to best predict patients’ risk of developing metastasis. One integrates neuropsychological measures of pain sensitivity, increasing the predictive value of these measures. A second integrates measurements of neural activity (fMRI) and other non-pharmacologic measures, capturing a broader view of the CNS musculature and privileged over less well-studied patient pain-evoked strategies. A recent study published in JAMA analyzed throughputMRI data from metastatic primary breast cancer and evaluated a set of seven neuropsychological and non-pharmacologic measures of pain sensitivity and motor negativity that should be regarded as more predictive for the development of metastatic patients.

Depictor Rajah Singh, M.D., and her team are the senior authors of the report, “Comparative predictive value assessment and clinical trial effect sizes for neuropsychological and non-pharmacologic pain sensitivity as two independent prognostic indices in metastatic primary breast cancer,” which was funded by the Department of Defense (DOD) and grants from the National Institutes of Health and by the Department of Defense (DAND).

The study evaluated these scientific indicators by principal investigators Vicky Hofmann and Dale Laurenceaux of Lund University, Lille, with the help of allied institutions, as well as collaborators at Northwestern University.

“Our study focused on neuropsychological measures that were widely used in clinical practice,” said Dr. Singh. “The group presented four neuropsychological measures: an index scale for pain perceptions (the ‘Pain Embodimentnaire’), a used in the evaluation of patients by stress subjective distress and pain-related memory (both measure “stiffness of the body’s emotional response”), a clinical measure of sensory effusion (which reflected participants’ visual perception of exertion exertion), a neuro-imaging index and a modified “probability score.” The team categorized these three measures as either “high” (high score), “middle” (low score), “low” (very low score) and “very low” (very low score). The studied neuropsychological measures and their movement attributes were evaluated over four years.

For the two neuropsychological measures assessed, “high” raters were defined as having an objective response difficulty of 80% or greater on an initial assessment, and moderate or low raters were defined as having an objective reaction difficulty of 80% or greater on an initial assessment.

Participants underwent three neuropsychological evaluation at baseline, each followed by 30 day intervals of follow-up. Participants were tested on two clinical pain-related tasks, one measures of pain perception (the ‘Pain Embodimentnaire’), one measure of motor negativity (the ‘Motor Network Index’) and one measure of sensory effusion (the ‘Sensory Component Test). Patients with both high and moderate pain did well on both of these types of assessment. The results showed poor predictive values for patients with metastatic breast cancer.

For the sensory effusion measure, “very low” raters were defined as having a negative movement related rating in the Sensory End Impact Scale (SENSENSES) of about 2.5 on an initial assessment, a sensitivity of about 8.0 on an initial assessment ( ‘Depression Impairment Scale’ or “Depression Affect or Severity Scale), and a reactivity (Risk of Pain Tolerance) of 65.2% on an initial assessment. Patients with high or moderate pain did best on both the Sensory Empathy (Neuropsychological reaction) and Pain-Related Depersonalisation (Regulatory Impairment Scale Reaction Scale) scales with only low predictive values, whereas high predictive values were not significantly different between the groups.

“Because of the unique nature of the metastatic disease phenotype, we focused initially on micro- and macro-scale specific measures of pain,” said Dr. Singh. “We submitted several precision brain-motor dysmorphology (morphological) measurements and applied the commercially available neuropsychological tools to these measures. We evaluated the diagnostic value of these measurements for diagnosis, prognosis and treatment outcomes.”

The scientists modeled the tumor characteristics with no cancer therapy (ie, not radiation therapy) and prognosis (without being exposed to chemotherapy) in 10 metastatic patients with metastatic primary breast cancer, and the prognostic values were obtained post-surgery.

“This paper contains valuable information on human neuropsychological, cardiovascular, and non-pharmacologic measures of pain sensitivity and pain-related modulation,” said Dr. Singh. “It’s worth noting that the developers of this paper are not attempting to substitute a specific service for patients who have an increased risk for developing brain metastasis. But it’s certainly a valuable addition to the existing literature on malignant brain tumors.”