Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals.
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.
Ansah
Osei B
OB
Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
Gonçalves
Leonor
L
Almeida
Armando
A
Pertovaara
Antti
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D012154:Reticular Formation / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid