Objective To observe the effect of moxibustion on pain and N-methyl-D aspartic acid receptor/nitric oxide/cyclic guanosine monophosphate(NMDA-NO-cGMP) signaling pathway in the spinal cord of rats with adjuvant arthritis(AA)

so as to explore its underlying mechanisms in relieving inflammatory pain of rheumatoid arthritis(RA). Methods SD rats were randomly divided into normal

model

moxibustion(Moxi)

Moxi +NMDA receptor antagonist AP-5(Moxi+AP-5) and Moxi +NMDA receptor agonist(NMDA) groups

with 20 rats in each group. The AA model was established by placing the rats in a wind

cold and damp environment for 12 h

once daily for 20 days and by injection of complete Freund's adjuvant into the right hind paw. Rats of the three Moxi groups received ignited moxa-stick stimulation of “Zusanli”(ST36) and “Shenshu”(BL23) alternately for 20 min

once a day for 15 days. The Moxi + AP-5 group and Moxi +NMDA group received intraperitoneal injection of AP-5(0.7 mg·kg

(-1)

·d(-1)·d

(-1)

) and NMDA(5 mg·kg(-1)) and NMDA(5 mg·kg

(-1)

·d(-1)·d

(-1)

)

respectively

once a day

for a total of 15 days. Mechanical pain thres-hold(MPT) was measured before and after modeling and interventions. The spinal cord tissue was sampled for detecting the expression of iNOS mRNA and protein

content of cGMP and NO

and the activity of NOS by using fluorescence quantitative PCR

Western blot

ELISA

nitrate reductase method and colorimetric method

respectively. Results Before modeling

there was no significant difference in MPT among all the 5 groups(P

>

0.05). After modeling

the MPT was remarkably decreased(P

<

0.01)

the expression levels of iNOS mRNA and protein

the contents of cGMP and NO

the activity of NOS were significantly increased in the model group relevant to the normal group(P

<

0.01). After the interventions

the MPT was obviously increased(P

<

0.01)

while the expression levels of iNOS mRNA and protein

the contents of cGMP and NO

the activity of NOS were significantly down-regulated in the Moxi

Moxi-AP-5 and Moxi+NMDA groups(P

<

0.05

P

<

0.01). The effect of Moxi+AP-5 group was significantly superior to that of Moxi group in raising MPT and down-regulating the expression levels of iNOS mRNA and protein

and the content of NO(P

<

0.05

P

<

0.01). The effect of Moxi+NMDA group was obviously inferior to that of Moxi group in up-regulating MPT and down-regulating the levels of iNOS mRNA and protein

and the contents of cGMP and NO

and the activity of NOS(P

<

0.01)

suggesting a reduction of the therapeutic effects in raising MPT and down-regulating expression of iNOS mRNA and protein after administration of AP-5. Conclusion Moxibustion can relieve RA inflammatory pain in AA rats

which may be related to its function in down-regulating the NMDA/NO/cGMP signaling pathway in the spinal cord.