Open Access Highly Accessed Research article

Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

Kitaro Onozawa1, Yuki Yagasaki2, Yumi Izawa2, Hiroyuki Abe1 and Yoriko Kawakami2*

Author Affiliations

1 Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, 116-8567, Japan

2 Department of Physiology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

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BMC Neuroscience 2011, 12:115  doi:10.1186/1471-2202-12-115

Published: 15 November 2011



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.