Different Brain Circuitries Mediating Controllable and Uncontrollable Pain

Abstract

Uncontrollable, compared with controllable, painful stimulation can lead to increased pain perception and activation in pain-processing brain regions, but it is currently unknown which brain areas mediate this effect. When pain is controllable, the lateral prefrontal cortex (PFC) seems to inhibit pain processing, although it is unclear how this is achieved. Using fMRI in healthy volunteers, we examined brain activation during controllable and uncontrollable stimulation to answer these questions. In the controllable task, participants selfadjusted temperatures applied to their hand of pain or warm intensities to provoke a constant sensation. In the uncontrollable task, the temperature time courses of the controllable task were replayed (yoked control) and participants rated their sensation continuously. During controllable pain trials, participants significantly downregulated the temperature to keep their sensation constant. Despite receiving the identical nociceptive input, intensity ratings increased during the uncontrollable pain trials. This additional sensitization was mirrored in increased activation of pain-processing regions such as insula, anterior cingulate cortex, and thalamus. Further, increased connectivity between the anterior insula and medial PFC (mPFC) in the uncontrollable and increased negative connectivity between dorsolateral PFC (dlPFC) and insula in the controllable task were observed. This suggests a pain-facilitating role of the mPFC during uncontrollable pain and a pain-inhibiting role of the dlPFC during controllable pain, both exerting their respective effects via the anterior insula. These results elucidate neural mechanisms of context-dependent pain modulation and their relation to subjective perception.

Building better biomarkers: brain models in translational neuroimaging

“…One process was evoked pain sensitivity, which is a feature of multiple pain-related disorders 112–114 . Wager et al developed an fMRI-based signature for evoked pain, called the Neurologic Pain Signature (NPS) 23 , which is sensitive and specific to pain across a number of conditions 23,24,115,116 and which generalizes to multiple types of acute pain across studies and diverse populations 115,117,118 (Fig. 4c).…”

“…Bottom: the NPS’s ‘psychological receptive field’, which visualizes conditions that activate (sensitivity, in orange and red) or do not activate (specificity, in gray and black) the NPS. Dark colored conditions (in red and black) are from published results 23,24,115–118 , and light colored conditions (in orange and gray) are from unpublished, preliminary results (data on cognitive demand were tested by C.-W.W.; visceral and vaginal pain data were tested by T.D.W.). Characterizing the NPS’s sensitivity and specificity across these conditions and others aides in understanding what NPS alterations in clinical disorders mean from a psychological and functional perspective.…”

The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain

“…Furthermore, perceived control of pain was associated with activation of the right DLPFC 109 . Relatedly, Brascher et al reported that uncontrollable pain resulted in increased activation of pain-related areas including the thalamus and insula, but that bilateral DLPFC had increased negative connectivity strength during controllable pain to both the thalamus and right anterior insula 12 . In other words, the DLPFC suppressed insula and thalamus activity and reduced pain sensitization associated with uncontrollable pain.…”

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

“…Third, an imaging neuromarker might not generalize to all types of pain, or to all individuals; this aspect must also be tested empirically. Fourth, prediction of pain does not imply a causal relationship between the predictive activity and the experience of pain.Most work to date has involved attempts to identify neuromarkers that reflect mechanisms and neurophysiological processes that are important in chronic pain 31,64,[77][78][79][80][81] . Given that the experience of pain has diverse influences, from nociception to social context, it is very unlikely that a single neuromarker will be found to reflect all aspects of acute and chronic pain in all contexts.…”