Activation of α1 adrenoceptors in ventrolateral orbital cortex attenuates allodynia induced by spared nerve injury in rats.
Recent studies have demonstrated that noradrenaline acting in the ventrolateral orbital cortex (VLO) can potentially reduce allodynia induced by spared nerve injury (SNI), and this effect is mediated by α2 adrenoceptor. The present study examined the effect of the α1 adrenoceptors in the VLO on allodynia induced by SNI in the rats. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of selective α1 adrenoceptor agonist methoxamine (20, 50, 100 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, increased PWT in a dose-dependent manner. This effect was antagonized by pre-microinjection of the selective α1 adrenoceptor antagonist benoxathian into the same VLO site, and blocked by electrolytic lesion of the ventrolateral periaqueductal gray (PAG). Furthermore, pre-administration of non-selective glutamate receptor antagonist kynurenic acid, phospholipase C (PLC) inhibitor U73122, and protein kinase C (PKC) inhibitor chelerythrine to the VLO also blocked methoxamine-induced inhibition of allodynia. These results suggest that activation of α1 adrenoceptors in the VLO can potentially reduce allodynia induced by SNI. This effect may be direct excitation of the VLO neurons, via PLC-PKC signaling pathway, projecting to the PAG or facilitating glutamate release and then indirectly exciting the VLO output neurons projecting to the PAG, leading to activation of the PAG-brainstem descending inhibitory system which depresses the nociceptive transmission at the spinal cord level.
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Division of Forensic Medicine, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Lai
L
Wei
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Yuan-Mei
YM
Zhu
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Yu-Xiang
YX
Zhang
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Feng
F
Liang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Hong
H
Jia
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Chao-Ling
CL
Qu
Key Laboratory of Orthopedics of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
Jing
J
Wang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
Jing-Shi
JS
Tang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
She-Min
SM
Lu
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China. Electronic address: huofq@mail.xjtu.edu.cn.
Fu-Quan
FQ
Huo
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China. Electronic address: yanchunxia@mail.xjtu.edu.cn.
Chun-Xia
CX
Yan
D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage; D000818:Animals; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D008845:Microinjections; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010543:Peroneal Nerve / Q000293:injuries; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D013497:Sural Nerve / Q000293:injuries; D013979:Tibial Nerve / Q000293:injuries
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1
Neuropathic pain; PKC; PLC; Periaqueductal gray; Ventrolateral orbital cortex; α(1) adrenoceptor