Abstract
Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.
Highlights
The perception of pain has two major features: a sensorydiscriminative component that processes the modality, location and intensity of the noxious stimulus, and an affective/emotional component that is critical to the aversive/unpleasant quality of an ongoing pain experience
Previous studies in the rat demonstrated that lesions of or microinjections of gabapentin into the rACC alleviate the aversive quality of the pain experience, without interrupting its sensory discriminative aspects; i.e. mechanical hypersensitivity persists (Johansen et al, 2001; Qu et al, 2011; Bannister et al, 2017)
To determine if this relationship holds true in mice, we first studied the effect of ibotenic acid-induced excitotoxic lesions of the rACC on three measures of the sensory/discriminative component of pain: (i) hindpaw withdrawal latency to a noxious radiant heat stimulus; (ii) nocifensive behaviours induced by hindpaw injection of formalin, a noxious inflammatory stimulus; and (iii) mechanical withdrawal thresholds before and after partial nerve injury
Summary
The perception of pain has two major features: a sensorydiscriminative component that processes the modality, location and intensity of the noxious stimulus, and an affective/emotional component that is critical to the aversive/unpleasant quality of an ongoing pain experience. The rostral anterior cingulate cortex (rACC), insular cortex and amygdala are implicated in processing of the affective component of the pain experience (Price, 2000).
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