The role of the dopamine D2 receptor in descending control of pain induced by motor cortex stimulation in the neuropathic rat.
We studied in rats with a spinal nerve ligation-induced neuropathy whether dopamine D2 receptors (D2Rs) play a role in descending control of pain induced by stimulation of the primary motor cortex (M1). Noxious heat-evoked responses were determined in spinal dorsal horn wide-dynamic range (WDR) and nociceptive-specific (NS) neurons, with and without electrical M1 stimulation. A D2R antagonist, raclopride, was administered into the dorsal striatum or spinally in attempts to reverse spinal antinociception induced by M1 stimulation. Moreover, influence of M1 stimulation on the noxious heat-induced limb withdrawal reflex was determined following block of spinal D2Rs with raclopride or a lidocaine-induced block of the hypothalamic A11 cell group, the main source of spinal dopamine. Striatal administration of raclopride enhanced the heat-evoked baseline responses of WDR but not NS neurons and reversed the M1 stimulation-induced suppression of the heat response in WDR neurons. Following spinal administration of raclopride, M1 stimulation failed to suppress the heat response of WDR neurons, whereas the heat response of NS neurons was enhanced by M1-stimulation. After blocking the A11 with lidocaine or spinal D2Rs with raclopride, M1 stimulation failed to suppress the noxious heat-evoked withdrawal reflex. The results indicate that descending pain control induced by stimulation of the M1 cortex in neuropathic animals involves supraspinal (presumably striatal) and, through A11, spinal D2Rs. Supraspinal and spinal D2Rs have partly dissociative effects on spinal dorsal horn WDR and NS neurons, possibly reflecting differential roles and wirings that these sensory neurons have in pain-processing circuitries.
Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, FIN-00014 Helsinki, Finland.
Hanna
H
Viisanen
Osei Bonsu
OB
Ansah
Antti
A
Pertovaara
D000704:Analysis of Variance; D000818:Animals; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology; D006358:Hot Temperature; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000628:therapy; D010880:Piperidines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012018:Reflex / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D018492:Dopamine Antagonists; D007211:Indoles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D020891:Raclopride; C104750:3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole