Amygdala group II mGluRs mediate the inhibitory effects of systemic group II mGluR activation on behavior and spinal neurons in a rat model of arthritis pain
There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
The amygdala plays a critical role in emotional-affective aspects of behaviors and
pain modulation. The central nucleus of amygdala (CeA) serves major output functions,
and neuroplasticity in the CeA is linked to pain-related behaviors in different models.
Activation of G i/o -coupled group II metabotropic glutamate receptors (mGluRs), which
consist of mGluR2 and mGluR3, can decrease neurotransmitter release and regulate synaptic
plasticity. Group II mGluRs have emerged as targets for neuropsychiatric disorders
and can inhibit pain-related processing and behaviors. Surprisingly, site and mechanism
of antinociceptive actions of systemically applied group II mGluR agonists are not
clear. Our previous work showed that group II mGluR activation in the amygdala inhibits
pain-related CeA activity, but behavioral and spinal consequences remain to be determined.
Here we studied the contribution of group II mGluRs in the amygdala to the antinociceptive
effects of a systemically applied group II mGluR agonist (LY379268) on behavior and
spinal dorsal horn neuronal activity, using the kaolin/carrageenan-induced knee joint
arthritis pain model. Audible and ultrasonic vocalizations (emotional responses) and
mechanical reflex thresholds were measured in adult rats with and without arthritis
(5–6 h postinduction). Extracellular single-unit recordings were made from spinal
dorsal horn wide dynamic range neurons of anesthetized (isoflurane) rats with and
without arthritis (5–6 h postinduction). Systemic (intraperitoneal) application of
a group II mGluR agonist (LY379268) decreased behaviors and activity of spinal neurons
in the arthritis pain model but not under normal conditions. Stereotaxic administration
of LY379268 into the CeA mimicked the effects of systemic application. Conversely,
stereotaxic administration of a group II mGluR antagonist (LY341495) into the CeA
reversed the effects of systemic application of LY379268 on behaviors and dorsal horn
neuronal activity in arthritic rats. The data show for the first time that the amygdala
is the critical site of action for the antinociceptive behavioral and spinal neuronal
effects of systemically applied group II mGluR agonists.