The ‘pain matrix’ may only be peripherally related to pain

In a small but noteworthy fMRI study, British and Chinese researchers have found that two individuals born with a rare inability to feel physical pain evidence the same patterns of brain activity when pricked with a pin as four healthy, age-matched volunteers.  

The finding, published as a research letter April 25 in JAMA Neurology, raises the question of whether the widely accepted “pain matrix”—considered a reliable biomarker for all manner of pain, including emotional distress—has much to do with pain per se.

Lead author Tim Salomons, PhD, of the University of Reading and colleagues describe their work using 3T fMRI to scan the brains of the six subjects while administering pain-inducing stimuli to the dorsum (backside) of the right hand.  

The four-person control group unanimously reported the stimuli as painful, recording the pain level at a mean of 3.2 on a scale of 0 (no pain) to 10 (intense pain), while the two pain-free individuals reported no perceptions of pain at all.

Meanwhile, in both pain-free individuals, the fMRI revealed normal activation of brain regions commonly activated by painful stimuli—the pain matrix—and there was no significant difference between patients and control individuals either across the entire pain matrix or in key pain-matrix regions.

In their discussion, Salomons et al. write that their observations “reinforce the need for caution in using pain-matrix responses for diagnosis or drug discovery,” adding that the findings “corroborate evidence that reported correlations between neuroimaging data and perceived pain have largely relied on non-pain-specific activities.”

“Examining how the brain gives rise to the unique perceptual experience of pain will require human neuroimaging to be supplemented by techniques that allow for causal inferences,” they conclude. “These include studies in nonhuman species where cell populations and circuitry can be genetically or chemically modified and human studies of individuals with relevant lesions or genetic mutations.”

Commenting on the study in the same edition of JAMA Neurology, Paul Geha, MD, and Stephen Waxman, MD, PhD, both of Yale, note that the results of the Salomons study add fuel to the doubts some have raised over the concept of the pain matrix.

“In fact, their demonstration of activity in the pain matrix without pain is in line with the observation that areas of the pain matrix are highly interconnected at rest, in the absence of any peripheral input,” write Geha and Waxman, “and form parts of one of the major resting-state brain networks.”

While acknowledging the major progress that has been made in this field over the past two decades, Geha and Waxman point out that the neuroscience community remains “unable to understand how conscious perception of pain arises, especially since there is no specialized brain tissue responding specifically to nociceptive input, like the primary somatosensory cortex responds to touch.”