Adenosine A2a Receptors Mediate Anti-nociceptive Effects Of Moxibustion

Objective:To observe whether adenosine A2 a receptors mediate the anti-nociceptive effects of moxibustion on inflammatory pain.Methods:C57BL/6J mice were used in these experiments.We chose the thermal test to filtrate the basic thermal threshold of mice between 10~16s.Then,the mice that filtrated the basic thermal threshold were randomly divided into control group and model group.Peripheral inflammation was induced by injection of complete Freund’s adjuvant(CFA)(20 μL)into the plantar surface of right hind paw of mice.Moreover,the mice of model group were randomly divided into CFA group,CFA+CGS21680 group,CFA+ SCH58261 group,CFA+MOXI group,CFA+MOXI+CGS21680 group,CFA+MOXI+SCH58261 group.CGS21680 or SCH58261 was injected into Zusanli point(ST36)and restrained 15 min at the forth day.Moxibustion was administered for 15 min at ST36 at the forth day.Behavioral parameters were evaluated before intraplantar injection of CFA(basic thermal threshold line).At the forth day,before moxibustion,these mice(CFA+CGS21680 group,CFA+ SCH58261 group,CFA+MOXI+CGS21680 group,CFA+MOXI+SCH58261 group)were injected CGS21680 or SCH58261.15 min later,we started to measure the thermal threshold for 2h.2 hours later,we picked up the hypothalamus to check out the A2 a R mRNA expression.Statistical analysis software was SPSS23.0 and GraphPad Prism 6.Results:1.The effect of moxibustion on inflammation pain model at ST36Compared with control group,CFA group showed a sharp decrease on the thermal threshold(P<0.05);compared with CFA group,CFA+MOXI group showed a increase.At 30 min,the thermal threshold reached the peak value.During 60~120min,the thermal threshold showed a decrease.Within 0~90min,the increasing thermal threshold was statistically significant(P<0.05).2 The effect of adenosine A2 a receptor on moxibustion-induced analgesia at ST36(1)The ST36 effect of A2 a receptor agonist or antagonist on CFA group: Compared with the CFA group,CFA+CGS21680 group showed a shape decrease on the thermal threshold during 0~120min(P<0.05).Compared with the CFA group,CFA+SCH58261 group showed a shape increase on the thermal threshold at 0min(P<0.05).After 30 min,the thermal threshold turned back to the level of CFA group,there was no statistically significant(P>0.05).(2)The effect of A2 a receptor agonist on moxibustion-induced analgesia at ST36:(1)Compared with the CFA+MOXI group,CFA+MOXI+CGS21680 group showed a decrease on the thermal threshold during 0~120min(P<0.05).(2)Compared with the CFA+ CGS21680 group,CFA+MOXI+CGS21680 group showed the fine increase of thermal threshold.There was a statistically significant at 0min and 30min(P<0.05).(3)The effect of A2 a receptor antagonist on moxibustion-induced analgesia at ST36(1)Compared with the CFA+MOXI group,CFA+MOXI+SCH58261 group showed a higher thermal threshold at 0min(P<0.05).Then,the thermal threshold went down.(2)Compared with the CFA+ SCH58261 group,CFA+ MOXI+SCH58261 group showed an increase of the thermal threshold.The thermal threshold of CFA+ MOXI+SCH58261 group was shorter than CFA+SCH58261 group at 0min(P>0.05).During the 30~120min,the thermal threshold of CFA+MOXI+SCH58261 group went down.At 30 min,the thermal threshold was higher than CFA+SCH58261 group(P<0.05).3 The changes of A2 a R mRNA expression in hypothalamusCompared with control group,the expression of A2 a R mRNA of CFA group was decreased(P<0.05).Compared with CFA group,the expression of A2 a R mRNA of CFA+MOXI group was increased(P<0.05).Conclusions:1.Moxibustion has a good analgesia effect on CFA-induced model;2.Adenosine A2 a receptors mediate local anti-nociceptive effects of moxibustion;(1)Activation of adenosine A2 a receptor of local acupoint were block almost the analgesic effect of moxibustion at ST36.(2)Antagonism of adenosine A2 a receptor of local acupoint were strengthen the analgesic effect of moxibustion at ST36.3.Adenosine A2 a receptor of hypothalamus would mediate anti-nociceptive effects of moxibustion.