Peripheral neuropathy has been associated with structural and functional changes of the amygdala, a key player in emotions. Here we study whether
peripheral neuropathy influences
pain regulation by the amygdala. For this purpose, we determined discharge rates of presumably pro- and antinociceptive
pain-regulatory neurons in the rostral ventromedial medulla (RVM) following microinjection of various glutamatergic compounds into the central nucleus of the amygdala. RVM neurons were recorded in
pentobarbitone-anesthetized rats with a
peripheral nerve injury or
sham-operation. In a separate behavioral experiment, we determined whether the influence of amygdaloid administration of a glutamatergic compound on affective
pain-related behavior, as assessed by an aversive place-conditioning test, is changed by neuropathy. While
glutamate or an
NMDA receptor antagonist in the amygdala failed to induce marked changes in discharge rates of RVM cells, amygdaloid administration of
DHPG, a group I
metabotropic glutamate receptor (mGluR) agonist acting on mGluR(1) and mGluR(5), increased discharge rates of presumably pronociceptive RVM ON-cells in nerve-injured but not
sham-operated animals. This pronociceptive effect of
DHPG was reversed by MPEP (mGluR(5) antagonist) and
CPCCOEt (mGluR(1) antagonist). CHPG, an mGluR(5) agonist, failed to influence ON-cell activity and
DHPG failed to influence activity of presumably antinociceptive RVM OFF-cells. Amygdaloid administration of
DHPG increased and that of
CPCCOEt decreased affective
pain-related behavior in nerve-injured animals. The results suggest that following nerve injury, the amygdaloid group I mGluR, particularly subtype mGluR(1), has an enhanced pronociceptive effect providing a potential mechanism for emotional enhancement of
pain in
peripheral neuropathy.