Departments of Neurological Surgery and.
Departments of Neurological Surgery and
J Neurosci. 2019 Mar 13;39(11):2065-2079. doi: 10.1523/JNEUROSCI.2552-18.2019. Epub 2019 Jan 16.
There is strong evidence that spinoparabrachial neurons in the superficial dorsal horn contribute to persistent pain states, and that the lateral parabrachial complex (PB) conveys relevant nociceptive information to higher structures. The role of PB itself in hyperalgesia and how it recruits descending facilitation has nevertheless received significantly less attention. The current study is a first step toward delineating the functional dynamics of PB and its link to descending control in acute and persistent inflammatory pain. In lightly anesthetized rats, we recorded behavioral withdrawal evoked by mechanical stimulation of the hindpaw and, simultaneously, the activity of identified pain-modulating neurons, "ON-cells" and "OFF-cells," in the rostral ventromedial medulla (RVM). This was done before and after the inactivation of PB, contralateral or ipsilateral to an inflamed paw [1 h, 1 d, or 5-6 d after intraplantar injection of Complete Freund's Adjuvant (CFA)]. The inactivation of contralateral, but not ipsilateral, PB interfered with nociceptive input to RVM under basal conditions, as well as in acute inflammation. By contrast, blocking ipsilateral, but not contralateral, PB in established inflammation interfered with behavioral hyperalgesia and ON-cell and OFF-cell responses. The lesioning of contralateral PB before CFA injection prevented this recruitment of ipsilateral PB in persistent inflammation. These experiments show that contralateral PB is required to initiate hyperalgesia, which is then maintained by ipsilateral PB, most likely in both cases via the engagement of pain-modulating neurons of the RVM. The lateral parabrachial complex (PB) relays nociceptive information to brain circuits that are important for the transmission and modulation of pain, but its specific role in persistent pain and engagement of descending control mechanisms has received relatively little attention. We show here that PB contralateral and ipsilateral to an inflammatory insult demonstrate different functions as inflammation persists, likely by engaging pain-facilitating neurons of the rostral ventromedial medulla. While the contralateral PB, the target of the major spinoparabrachial pathway, relays acute nociceptive information, the ipsilateral PB is recruited or unmasked in persistent inflammation to maintain hyperalgesia. These data point to plasticity in the PB itself or its direct and indirect connections with pain-modulating systems as central to the development and maintenance of persistent pain.
有强有力的证据表明，浅层背角中的脊髓-臂旁神经元有助于持续性疼痛状态，并且外侧臂旁复合核（PB）将相关的伤害性信息传递到更高的结构。然而，PB 本身在痛觉过敏中的作用以及它如何招募下行促进作用，却受到了较少的关注。本研究是朝着描绘 PB 的功能动态及其与急性和持续性炎症性疼痛的下行控制之间联系的第一步。在轻度麻醉的大鼠中，我们记录了机械刺激后后爪引起的行为退缩，并同时记录了头端腹内侧髓（RVM）中已识别的疼痛调节神经元“ON 细胞”和“OFF 细胞”的活性。这是在 PB 同侧或对侧（足底注射完全弗氏佐剂（CFA）后 1 小时、1 天或 5-6 天）之前和之后进行的。对侧 PB 的失活不仅在基础条件下，而且在急性炎症中，都干扰了对 RVM 的伤害性传入。相比之下，在已建立的炎症中阻断同侧 PB，但不阻断对侧 PB，会干扰行为性痛觉过敏以及 ON 细胞和 OFF 细胞的反应。在 CFA 注射前对侧 PB 的损伤可防止在持续性炎症中招募同侧 PB。这些实验表明，对侧 PB 是引发痛觉过敏所必需的，而随后由同侧 PB 维持，在这两种情况下，很可能都是通过 RVM 中的疼痛调节神经元的参与。外侧臂旁复合核（PB）将伤害性信息传递到大脑回路，这些回路对于疼痛的传递和调制很重要，但它在持续性疼痛和下行控制机制的参与中的特定作用相对较少受到关注。我们在这里表明，在炎症持续存在的情况下，同侧和对侧 PB 表现出不同的功能，可能是通过参与头端腹内侧髓的疼痛促进神经元。虽然对侧 PB 是主要的脊髓-臂旁通路的靶点，传递急性伤害性信息，但在持续性炎症中，同侧 PB 被招募或暴露出来，以维持痛觉过敏。这些数据表明，PB 本身或其与疼痛调节系统的直接和间接连接的可塑性是持续性疼痛的发展和维持的核心。
