Abstract: BACKGROUND: Acupuncture is an effective method for lumbar pain in lumbar disc herniation, but its mechanism has not yet been clarified. Factors related to the JAK2/STAT3 signaling pathway regulate the body’s inflammatory response and are involved in the process of neuropathic pain.
OBJECTIVE: To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. 
METHODS: Forty Sprague-Dawley rats were randomly divided into four groups: sham operation group, model group, acupuncture group, and acupuncture+agonist group, with 10 rats in each group. Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group, acupuncture group, and acupuncture+agonist group. Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment (Yanglingquan, Shenshu, Huantiao, and Dachangshu acupoints) at 3 days after modeling, and acupuncture treatment was given once a day, 20 minutes each, for 15 consecutive days. Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1, a JAK2 agonist, into the L4/L5 intervertebral space, once a day, 20 minutes each, prior to the acupuncture at 6, 12, and 18 days after modeling. Paw withdrawal mechanical threshold was detected before and 3, 6, 9, 12, 15, and 18 days after modeling. At 18 days after modeling, serum inflammatory factor levels were detected, hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues, RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues, and western blot was performed to detect the expression of JAK2, p-JAK2 and p-STAT3 proteins in L5-L6 tissues. 
RESULTS AND CONCLUSION: The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group (P < 0.05), the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9, 12, 15, and 18 days after modeling (P < 0.05), and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9, 12, 15, and 18 days after modeling (P < 0.05). The levels of interleukin 6, tumor necrosis factor α, neurotransmitter substance P, and brain neuropeptide Y were elevated in the model group compared with the sham operation group (P < 0.05); the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group (P < 0.05); and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group (P < 0.05). Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group. Moreover, the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group. The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group (P < 0.05), were decreased in the acupuncture group compared with the model group (P < 0.05), and were increased in the acupuncture+agonist group compared with the acupuncture group (P < 0.05). To conclude, acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation, and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Key words: JAK2/STAT3 signaling pathway, acupuncture, lumbar disc herniation, pathologic pain, paw withdrawal mechanical threshold, inflammation