• Feni Kadakia, Akansha Khadka, Jacob Yazell, and Steve Davidson.
• Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Anesthesiology and Pain Research Center, University of Cincinnati, College of Medicine, Cincinnati, Ohio.
• J Pain. 2024 Mar 1; 25 (3): 766780766-780.

AbstractThe posterior insular cortex (PIC) is well positioned to perform somatosensory-limbic integration; yet, the function of neuronal subsets within the PIC in processing the sensory and affective dimensions of pain remains unclear. Here, we employ bidirectional chemogenetic modulation to characterize the function of PIC CaMKIIa-expressing excitatory neurons in a comprehensive array of sensory, affective, and thermoregulatory behaviors. Excitatory pyramidal neurons in the PIC were found to be sensitized under inflammatory pain conditions. Chemogenetic activation of excitatory CaMKIIa-expressing PIC neurons in non-injured conditions produced an increase in reflexive and affective pain- and anxiety-like behaviors. Moreover, activation of PIC CaMKIIa-expressing neurons during inflammatory pain conditions exacerbated hyperalgesia and decreased pain tolerance. However, Chemogenetic activation did not alter heat nociception via hot plate latency or body temperature. Conversely, inhibiting CaMKIIa-expressing neurons did not alter either sensory or affective pain-like behaviors in non-injured or under inflammatory pain conditions, but it did decrease body temperature and decreased hot plate latency. Our findings reveal that PIC CaMKIIa-expressing neurons are a critical hub for producing both sensory and affective pain-like behaviors and important for thermoregulatory processing. PERSPECTIVE: The present study reveals that activation of the posterior insula produces hyperalgesia and negative affect, and has a role in thermal tolerance and thermoregulation. These findings highlight the insula as a key player in contributing to the multidimensionality of pain.Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

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