Kadakia Feni, Khadka Akansha, Yazell Jacob, Davidson Steve
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.
Department of Anesthesiology and Pain Research Center, University of Cincinnati, College of Medicine, Cincinnati, Ohio.
J Pain. 2024 Mar;25(3):766-780. doi: 10.1016/j.jpain.2023.10.005. Epub 2023 Oct 11.
The 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.
后岛叶皮质（PIC）处于执行体感-边缘系统整合的有利位置；然而，PIC内神经元亚群在处理疼痛的感觉和情感维度方面的功能仍不清楚。在这里，我们采用双向化学遗传调制来表征PIC中表达CaMKIIa的兴奋性神经元在一系列感觉、情感和体温调节行为中的功能。我们发现，在炎症性疼痛条件下，PIC中的兴奋性锥体神经元会被致敏。在未受伤的情况下，对表达兴奋性CaMKIIa的PIC神经元进行化学遗传激活，会使反射性和情感性疼痛及焦虑样行为增加。此外，在炎症性疼痛条件下激活表达PIC CaMKIIa的神经元会加剧痛觉过敏并降低疼痛耐受性。然而，化学遗传激活并未通过热板潜伏期或体温改变热伤害感受。相反，抑制表达CaMKIIa的神经元在未受伤或炎症性疼痛条件下既不会改变感觉性或情感性疼痛样行为，但会降低体温并缩短热板潜伏期。我们的研究结果表明，表达PIC CaMKIIa的神经元是产生感觉性和情感性疼痛样行为的关键枢纽，对体温调节过程也很重要。观点：本研究表明，激活后岛叶会产生痛觉过敏和负面影响，并在热耐受性和体温调节中起作用。这些发现突出了岛叶在导致疼痛多维度方面的关键作用。
