Wan Juan, Qiu Zhengying, Ding Yi, Nan Sha, Ding Mingxing
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China.
Front Neurosci. 2018 Dec 13;12:902. doi: 10.3389/fnins.2018.00902. eCollection 2018.
To investigate dynamic processes of enkephalin (ENK), cholecystokinin octapeptide (CCK-8), orphanin FQ (OFQ) and their receptors (μ opioid receptor, MOR; CCK B type receptor, CCKBR and opioid receptor-like 1 receptor, OPRL1) in the central nerve system (CNS) during electroacupuncture (EA) tolerance, EA of Sixty Hz was used to stimulate goats for 6 h. Pain threshold was measured using potassium iontophoresis. The expression levels of ENK, CCK-8, and OFQ and their receptors were determined with ELISA and qPCR, respectively. The results showed that the change rates of pain threshold in EA-treated goats decreased from 89.9 ± 11.7% at 0.5 h to -11.4 ± 8.9% at 6 h. EA induced the decreased ENK and increased CCK-8 and OFQ in the most measured nuclei. EA caused decreased preproenkephalin mRNAs in ACB, CAU, PVH, and PAG at 4 h, and decreased or unchanged MOR mRNAs at 2-6 h, but increased CCK mRNAs in CAU, PVT, PVH, PAG, and SCD at 4-12 h. Increased prepronociceptin mRNAs and fluctuated CCKBR and OPLR1 mRNAs were found in the most measured nuclei. ENK levels were positively correlated ( < 0.01) with the change rates of pain thresholds in the measured nuclei or areas while CCK-8 levels (or OFQ levels) were negatively correlated ( < 0.01) with the pain thresholds in CAU (or CAU and ACB). These results suggest that the development and recovery of EA tolerance may be associated with the specific expression patterns of opioid peptides, anti-opioid peptides and their receptors in the analgesia-related nuclei or areas.
为研究电针(EA)耐受过程中脑啡肽(ENK)、八肽胆囊收缩素(CCK - 8)、孤啡肽(OFQ)及其受体(μ阿片受体,MOR;CCK B型受体,CCKBR;阿片样受体1,OPRL1)在中枢神经系统(CNS)中的动态变化过程,采用60Hz电针刺激山羊6小时。用钾离子透入法测量痛阈。分别用ELISA和qPCR法测定ENK、CCK - 8和OFQ及其受体的表达水平。结果显示,电针处理的山羊痛阈变化率从0.5小时时的89.9±11.7%降至6小时时的 - 11.4±8.9%。电针使大多数被测核团中ENK减少,CCK - 8和OFQ增加。电针在4小时时使伏隔核(ACB)、尾状核(CAU)、室旁核(PVH)和中脑导水管周围灰质(PAG)中前脑啡肽mRNA减少,在2 - 6小时时使MOR mRNA减少或不变,但在4 - 12小时时使CAU、丘脑室旁核(PVT)、PVH、PAG和视交叉上核(SCD)中CCK mRNA增加。在大多数被测核团中发现前痛敏肽原mRNA增加,CCKBR和OPLR1 mRNA波动。ENK水平与被测核团或区域的痛阈变化率呈正相关(<0.01),而CCK - 8水平(或OFQ水平)与CAU(或CAU和ACB)中的痛阈呈负相关(<0.01)。这些结果表明,电针耐受的形成和恢复可能与镇痛相关核团或区域中阿片肽、抗阿片肽及其受体的特定表达模式有关。