The role of dopamine receptors in ventrolateral orbital cortex-evoked anti-nociception in a rat model of neuropathic pain.
The present study examined the role of dopamine and D(1)-and D(2)-like dopamine receptors in ventrolateral orbital cortex (VLO)-evoked anti-hypersensitivity in a rat model of neuropathic pain, as well as the possible underlying mechanisms. Results showed that microinjection of apomorphine [(R(-)-apomorphine hydrochloride)], a non-selective dopamine receptor agonist, into the VLO attenuated spared nerve injury (SNI)-induced mechanical allodynia in a dose-dependent manner. This effect was completely blocked by the D(2)-like dopamine receptor antagonist S(-)-raclopride(+)-tartrate salt (1.5 microg), but was enhanced by the D(1)-like dopamine receptor antagonist SCH23390 (R(+)-SCH-23390 hydrochloride, 5.0 microg). The attenuating effect of apomorphine on mechanical allodynia was mimicked by application of the D(2)-like dopamine receptor agonist quinpirole [((-)-quinpirole hydrochloride, 0.5, 1.0, and 2.0 microg)]. In addition, microinjection of larger doses (10 and 20 microg) of SCH23390 into the VLO significantly attenuated allodynia. Furthermore, microinjections of GABA(A) receptor antagonists, bicuculline [(+)-bicuculline,(S), 9(R)] and picrotoxin (200 and 300 ng for both drugs), into the VLO attenuated mechanical allodynia. A small dose of bicuculline or picrotoxin (100 ng) resulted in increased quinpirole (0.5 microg)-induced anti-allodynia. In contrast, GABA(A) receptor agonists, muscimol hydrochloride (250 ng) or THIP [(2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride, 1.0 microg)], blocked quinpirole (2.0 microg)-induced attenuation. These results suggest that the dopaminergic system is involved in mediating VLO-induced anti-hypersensitivity, activation of D(2)-like dopamine receptors, and inhibition of D(1)-like receptors resulting in anti-hypersensitivity. In addition, the mechanisms of GABAergic disinhibition might be involved in D(2)-like receptor mediating effects in neuropathic pain.
Dang
Y H
YH
Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Yanta Road West 76#, Xi'an, Shaanxi 710061, PR China.
Zhao
Y
Y
Xing
B
B
Zhao
X J
XJ
Huo
F Q
FQ
Tang
J S
JS
Qu
C L
CL
Chen
T
T
D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*
D011954:Receptors, Dopamine; D004298:Dopamine