Department of Oral and Maxillofacial Surgery, Tokyo Women’s MedicalUniversity Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, 116-8567, Japan.
BMC Neurosci. 2011 Nov 15;12:115. doi: 10.1186/1471-2202-12-115.
We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC). The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA) to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS) delivered to the BLA on nociceptive responses in the rat PFC.
HFS induced long lasting suppression (LLS) of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA) receptor antagonists (2-amino-5-phosphonovaleric acid (APV), dizocilpine (MK-801)) and also metabotropic glutamate receptor (mGluR) group antagonists (α-methyl-4-carboxyphenylglycine (MCPG), and 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine (LY341495)), prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA) on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA) injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride) and D4 (3-{[4-(4-chlorophenyl) piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870)), microinjected into the PFC, inhibited LLS of nociceptive responses.
Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.
我们之前的研究表明，在额前皮质（PFC）中，机械性伤害性刺激会引发伤害性放电。在 PFC 中记录到的伤害性反应可能与疼痛的情感维度而非感觉辨别维度有关。PFC 从边缘系统接收密集的投射。已知杏仁核基底外侧核（BLA）到 PFC 的单突触投射会产生持久的突触可塑性。我们研究了高频刺激（HFS）施加于 BLA 对大鼠 PFC 伤害性反应的影响。
HFS 诱导了 PFC 中特定高阈值伤害性神经元反应的持久抑制（LLS）。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（2-氨基-5-磷基戊酸（APV），地卓西平（MK-801））和代谢型谷氨酸受体（mGluR）组拮抗剂（α-甲基-4-羧基苯甘氨酸（MCPG），2-[[1S，2S]-2-羧基环丙基]-3-（9H-香豆素-9-基）-D-丙氨酸（LY341495））的微注射可防止伤害性反应 LLS 的诱导。我们还研究了多巴胺（DA）对伤害性反应 LLS 的调节作用。在同侧前脑束中注射 6-羟多巴胺（6-OHDA）以耗尽 DA 后，伤害性反应的 LLS 减少，而正常诱发伤害性反应。PFC 中微注射的 DA 受体亚型 D2（舒必利）和 D4（3-[[4-（4-氯苯基）哌嗪-1-基]甲基]-1H-吡咯并[2,3-b]吡啶（L-745,870））的拮抗剂，抑制了伤害性反应的 LLS。
我们的结果表明，BLA-PFC 通路抑制了 PFC 伤害性细胞活动，而 DA 系统改变了 BLA-PFC 的调节功能。
