Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception

Abstract

In humans, gamma-band oscillations in the primary somatosensory cortex (S1) correlate with subjective pain perception. However, functional contributions to pain and the nature of underlying circuits are unclear. Here we report that gamma oscillations, but not other rhythms, are specifically strengthened independently of any motor component in the S1 cortex of mice during nociception. Moreover, mice with inflammatory pain show elevated resting gamma and alpha activity and increased gamma power in response to sub-threshold stimuli, in association with behavioral nociceptive hypersensitivity. Inducing gamma oscillations via optogenetic activation of parvalbumin-expressing inhibitory interneurons in the S1 cortex enhances nociceptive sensitivity and induces aversive avoidance behavior. Activity mapping identified a network of prefrontal cortical and subcortical centers whilst morphological tracing and pharmacological studies demonstrate the requirement of descending serotonergic facilitatory pathways in these pain-related behaviors. This study thus describes a mechanistic framework for modulation of pain by specific activity patterns in the S1 cortex.

Modulating Brain Rhythms of Pain using Transcranial Alternating Current Stimulation (tACS)? A Sham-controlled Study in Healthy Human Participants

“…Second, tACS might be able to modulate neural oscillations but neural oscillations might not be causally involved in the processing of pain. This seems unlikely since optogenetic and invasive electrical modulations of neural oscillations in somatosensory and prefrontal brain areas effectively modulate acute and chronic pain in animals [43,51]. Third, tACS might in principle be able to modulate neural oscillations and pain but the tACS parameters used in the present study were not optimal.…”

“…[11,24,27,30,39,50]). Moreover, animal studies relying on optogenetics and invasive electrical stimulation have indicated that these changes of neural oscillations are causally involved in generating pain [43,51]. Thus, modulating neural oscillations to eventually modulate pain is a promising novel approach for the treatment of pain [15].…”

“…Furthermore, the optogenetic induction of gamma oscillations in the primary somatosensory cortex led to enhanced pain behavior indicating a causal role of gamma oscillations for pain [43]. However, although tACS at gamma frequencies is feasible [3,42], no study has explored the effects of gamma tACS on pain so far.…”

What goes up must come down: insights from studies on descending controls acting on spinal pain processing

“…Very recently, a preclinical study has shown that activity in the primary somatosensory cortex is able to enhance pain by recruitment of the 5HT3 receptor facilitatory system that we have discussed previously (Tan et al 2019). A key patient study in OA used imaging and psychophysics (Soni et al 2019) and consolidated many of the issues that we have covered in this review.…”

Dorsal Root Ganglion Stimulation Modulates Cortical Gamma Activity in the Cognitive Dimension of Chronic Pain

“…The role of neurophysiology in these processes has revealed a similarly overlapping feature of pain and cognition-cortical gamma oscillations. High-frequency gamma activity has long been associated with cognition and attention [8,9] but has also been shown to encode ongoing pain [10,11]. Moreover, surgically implanted devices such as spinal cord stimulation have shown the potential to modulate cortical gamma (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) activity [12], supporting the hypothesis of supraspinal mechanisms of action for spinal, and potentially peripheral, neuromodulation.…”