Adenosine A1 Receptors Mediate Anti-nociceptive Effects Of Moxibustion

ObjectiveTo determine whether adenosine A1 repoters mediate the analgesia effects of moxibustion by evaluating the effects of moxibustion on inflammatory pain in C57BL/6J mice.MethodsC57BL/6J mice were used in all experiments. Then using thermal test to select the basic pain threshold between 10 s and 16 s of mice,the mice with similar pain threshold were randomly divided into control group,model group.Peripheral inflammation was induced by injection of complete Freund's adjuvant ?CFA? ?20 u.L? in the plantar surface of the right hind paw of mice. CCPA or CPT was administered in Zusanli point?ST36? before moxibustion on the forth day.Moxibustion was administered for 15 min at ST36.Behavioral parameters were evaluated before intraplantar injection of CFA?that is,BL?,on day 4 in mice receiving the CFA injection,and after moxibustion, injection CCPA or CPT?that is,measure for 2 h,30 min once?.Two hours later,pick up the hypothalamus to check out the AiR mRNA expression in it.Results?1?The effect of moxibustion to inflammation pain model miceCompared with control group,CFA group evoked a sharp decrease in the threshold to thermal pain?P<0.05?;compared with CFA group, CFA+MOXI group evoked a sharp decrease in the threshold to thermal pain during 15-75min?P<0.05?.?2?The effect of adenosine A1 receptors on moxibustion-induced analgesia1)The effect of Ai receptors agonist on moxibustion-induced analgesia?In the CFA+CCPA group administration of adenosine A1 receptors agonist ?CCPA? in right Zusanli point?ST36? evoked a sharp increase in the threshold to thermal pain.CFA+CCPA 0.05 mM group pain threshold increased at 45-135min ?P<0.05,compared with before CCPA?.CFA+CCPA 0.1 mM and CFA+CCPA 0.2 mM group pain threshold increased at 15?135 min?P<0.05,compared with before CCPA?.?In the CFA+MOXI+CCPA group administration of CCPA in right Zusanli point?ST36? evoked a increase in the threshold to thermal pain.CFA+MOXI+CCPA 0.05 mM group pain threshold was not significant change?P>0.05,compared with CFA+MOXI group?.CFA+MOXI+CCPA 0.1 mM and CFA+MOXI+CCPA 0.2 mM group pain threshold increased at 15?135 min ?P?0.05,compared with CFA+MOXI group?.CFA+MOXI+CCPA 0.05 mM group pain threshold increased at 15-75 min ?P<0.05,compared with CFA+CCPA 0.05 mM group?,CFA+MOXI+CCPA 0.1 mM group pain threshold was upregulated at 15 min ?P<0.05, compared with CFA+CCPA 0.1 mM group?,CFA+MOXI+CCPA 0.2 mM group pain threshold increased at 45 min ?.P<0.05, compared with CFA+CCPA 0.2 mM group?.2)The effect of A1 receptors antagonist on moxibustion-induced analgesia?In the CFA+CPT group administration of A1 receptors antagonist ?CPT? in right Zusanli point?ST36? evoked a decrease in the threshold to thermal pain. CFA+CPT 75 nM and CFA+CPT 150 nM group pain threshold decreased at 15? 105min?P<0.05,comp-ared with before CPT?.CFA+CPT 300 nM group pain thres holddecreased at 15?135 min?P?0.05,compared with before CPT?.?In the CFA+MOXI+CPT group administration of CPT in right Zusanli point evoked a decrease in the threshold to thermal pain.CFA+MOXI+CPT 75nM, CFA+MOXI+CPT 150 nM and CFA+MOXI+CPT 300 nM group pain threshold decreased at 15?105 min?P<0.05, compared with CFA+MOXI group?. CFA+MOXI+ CPT 75 nM group and CFA+MOXI+CPT 150 nM group pain threshold increased at 15?75 min ?P<0.05?,CFA+MOXI+CPT 300 nM group pain thresholdincreased at 15?105 min ?P<0.05, compared with CFA+CPT 300 nM group?.?3?Changes of A1R mRNA expression in hypothalamusCompared with control group,the expression of A1R mRNA of CFA group was downreguleated 2.23-fold. Compared with CFA group,the expression of AiR mRNA of CFA+MOXI group was upregulated 4.26-fold.Conclusions1. Moxibustion has a good analgesia effect in inflammatory pain model;2. Adenosine Ai receptors mediate local anti-nociceptive effects of moxibustion;3. Hypothalamus adenosine A₁ receptors would mediate anti-nociceptive effects of moxibustion.