Abstract
Objective To investigate the effect of electroacupuncture (EA) on the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) in the spinal dorsal horn during morphine tolerance in rats.Methods Twenty-five healthy male Sprague-Dawley rats in which intrathecal (IT) catheters were successfully implanted with-out complications were randomly divided into 5 groups (n =5 each):group normal saline (NS) 10 μl IT twice a day × 7 days; group M morphine 10μg (10 μl) IT twice a day × 7 days; group MO morphine 10 μg + missense oligonucleotide (ODN) 10μg (10 μl) twice a day × 7 days; group AO morphine 10 μg + antisense ODN 10 μg (10μl) twice a day×7 days; group EA morphine 10 μg (10μl) twice a day×7 days + EA (frequency 2 Hz,wave length 1 ms,intensity 3 mA).EA of Yanglingquan and Zusanli lasting for 30 min was performed after first IT administration of morphine once a day for 7 days.Mechanical pain threshold (MPT) was measured before IT administration and at day 2,4,6 of IT administration and 1 day after the end of IT administration.The animals were sacrificed after the last MPT measurement,and L3-5 segments of the spinal cord were isolated to detect the expression of ERK1/2 and phosphor-ERK1/2 (p-ERK1/2) in the spinal dorsal horn by Western blot analysis.Results Morphine tolerance developed in groups M,MO and AO,and was lightest in group EA.Compared with group NS,the expression of p-ERK1/2 was significantly up-regulated in groups M and MO,the expression of ERK1/2 was down-regulated in group AO (P ＜ 0.05),and no significant change was found in the indexes mentioned above in group EA (P ＞ 0.05).Compared with groups M and MO,the expression of p-ERK1/2 and ERK1/2 was significantly down-regulated in group AO,and the expression of p-ERK1/2 was down-regulated in group EA (P ＜0.05).Compared with group AO,the expression of p-ERK1/2 and ERK1/2 was significantly up-regulated in group EA (P ＜ 0.05).Conclusion EA can inhibit chronic morphine tolerance-induced increased activity of ERK1/2 in the spinal dorsal horn and alleviate the development of morphine tolerance in rats. Key words: Extracellular signal-regulated MAP kinases; Electroacupuncture; Drug tolerance; Morphine
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