The laterocapsular division of the central nucleus of the amygdala (CeLC) has emerged as an important site of
pain-related plasticity and
pain modulation.
Glutamate and
neuropeptide receptors in the CeLC contribute to synaptic and behavioral changes in the
arthritis pain model, but the intracellular signaling pathways remain to be determined. This study addressed the role of PKA, PKC, and ERK in the CeLC. Adult male Sprague-Dawley rats were used in all experiments. Whole-cell patch-clamp recordings of CeLC neurons were made in brain slices from normal rats and from rats with a
kaolin/
carrageenan-induced monoarthritis in the knee (6 h postinduction). Membrane-permeable inhibitors of PKA (
KT5720, 1 microM; cAMPS-Rp, 10 microM) and ERK (
U0126, 1 microM) activation inhibited synaptic plasticity in slices from arthritic rats but had no effect on normal transmission in control slices. A PKC inhibitor (
GF109203x, 1 microM) and an inactive structural analogue of
U0126 (U0124, 1 microM) had no effect. The
NMDA receptor-mediated synaptic component was inhibited by
KT5720 or
U0126; their combined application had additive effects.
U0126 did not inhibit synaptic facilitation by
forskolin-induced PKA-activation. Administration of
KT5720 (100 microM, concentration in microdialysis probe) or
U0126 (100 microM) into the CeLC, but not striatum (placement control), inhibited audible and ultrasonic vocalizations and spinal reflexes of arthritic rats but had no effect in normal animals.
GF109203x (100 microM) and U0124 (100 microM) did not affect
pain behavior. The data suggest that in the amygdala PKA and ERK, but not PKC, contribute to
pain-related synaptic facilitation and behavior by increasing
NMDA receptor function through independent signaling pathways.