Shenzhen Key Laboratory of Drug Addiction, Shenzhen-Hong Kong Institute of Brain Science, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Zool Res. 2024 May 18;45(3):633-647. doi: 10.24272/j.issn.2095-8137.2023.412.
Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( ) (lPBN ) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
疼痛刺激会引发一线反射性防御反应，在许多情况下，还会引发二线恢复性行为，后者反映了组织损伤的感知和痛苦的缓解。外侧臂旁核（lPBN）由外部（elPBN）、背侧（dlPBN）和中央/上亚核（统称 slPBN）组成，接收来自脊髓投射神经元的感觉输入，在处理来自外部威胁和身体完整性破坏的情感信息方面发挥重要作用。然而，lPBN 神经元的组织规则尚不清楚，这些神经元在响应来自皮肤和深部组织的不同疼痛刺激时会引发不同的行为。在这项研究中，我们使用了区域特异性神经元耗竭或沉默方法，并结合一系列行为分析，表明表达 P 物质受体（）（lPBN）的 slPBN 神经元对于驱动由持续的有害热和机械刺激引起的与疼痛相关的自我护理行为至关重要，这些刺激施加于皮肤或骨骼/肌肉，而 elPBN 神经元对于驱动这种反应则是可有可无的。值得注意的是，lPBN 神经元对于形成持续的躯体疼痛诱导的负性教学信号和厌恶记忆是特异性必需的，但对于由外部威胁引起的恐惧学习或逃避行为则不是必需的。最后，lPBN 和 elPBN 神经元均有助于化学刺激物引起的伤害反应。我们的研究结果揭示了臂旁核基质的功能组织，这些基质在生理条件下，根据持续疼痛与外部危险的不同，驱动着不同的行为结果。
