| As a typical modern version of traditional acupuncture, electroacupuncture (EA) has been used successfully to ameliorate pain in various operations, especially for the treatment of chronic and persistent pain, due to its good analgesic and anti-inflammatory as well as anti-shock effect. However, clinical data strongly suggest that EA tolerance could be occurred during a long-term electric acupuncture with a fixed frequency, appearing as the gradual decline of acupuncture effect and the decrease in analgesic effect, thus reducing the clinical efficacy. Therefore, to explore the intrinsic causes and laws of acupuncture tolerance to avoid the occurrence of acupuncture tolerance phenomenon is of great important in clinical trials. As one of the most important neurotransmitter and/or modulators, the endogenous cholecystokinin octapeptide (CCK-8) is reported to be the most abundant peptide in the brain, associated in the cerebral cortex and related nuclei, according to researches on rat. The present study was performed to investigate the regularity of the CCK-8concentration changes in the related central nuclei of goats during acupuncture analgesia tolerance, and to clarify the relationship between the CCK-8concentration and pain during the above process, aiming at exploring the regulation mechanism of CCK-8during the EA analgesia tolerance process in ruminants, and thus to provide appropriate information for clinical application of EA in goat. Crossbred healthy adult goats weighing25～30kg and1～2years old were selected as animals, and60Hz was set as EA frequency."Baihui-Qijia" and "Ergen-San yang luo" points of goats were stimulated via EA at60Hertz, and the pain threshold of EA group was then measured by potassium ion penetration method at different time. Results showed the formation of tolerance occurred at0.5h after the continuous EA at60Hz, and the tolerance fully formed after2h; a minor fluctuations of a tolerance occurred at4h of EA. Tolerance began to recover immediately after the stop of EA, and fully recover after30h.Concentrations of endogenous CCK-8in the related central nuclei of brain such as PAG, accumbens, amygdale, corpus striatum, paraventricular ventromedial nuclei and hypothalamus were determined by competitive enzyme-linked immunosorbent assay. Results showed that the concentration of endogenous CCK-8in each related nuclei of EA group increased significantly compared with that of the control group during EA analgesia process (P<0.05).The most obvious change of CCK-8concentration was observed in PAG. Meanwhile, significant time-course changes of endogenous CCK-8 concentration occurred in all EA group during the above process (P<0.05). The maximum concentration peak in PAG, hypothalamus and hypothalamic paraventricular nuclei occurred at2h after continuous EA at60Hz,2.52,1.32and1.74times higher than that of control group, respectively. The maximum value of CCK-8concentration in amygdale, corpus striatum and anterior commissure appeared at about4h,1.71,2.48and1.67higher than that of control, respectively. These results indicated that endogenous CCK-8derived from the above nucleus are involved in the regulation of EA analgesia tolerance.Correlation analysis was carried out to further investigate the relationship between the endogenous CCK-8level in central nuclei of brain and the change rate of pain threshold during EA analgesia tolerance. It can be seen from the result that the change trend in CCK-8concentration was the opposite of that in the rate change of pain threshold. Non-linear relationships were found between the change rate of pain threshold and endogenous CCK-8concentrations in PAG (r=0.997), Amygdale (r=0.997), Corpus striatum (r=0.997) and Paraventricular ventromedial (r=0.999) nuclei during the above process. However, there were significant linear correlations between the CCK-8concentrations in each nuclei. These results indicated that the CCK-8in each nuclei not work alone but interacts with others as a comprehensive system in the regulation of acupuncture tolerance. |
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