Background: Central sensitization driven by glial activation-mediated neuroinflammation is recognized as a key mechanism in pain processing. Laser moxibustion using low-intensity laser irradiation of corresponding acupoints significantly relieves knee osteoarthritis (KOA) pain. However, the underlying mechanism of its effects on KOA pain is still not completely understood. Objective: In this study, we aimed to investigate whether laser moxibustion could alleviate KOA pain by inhibiting spinal glial activation and proinflammatory cytokines upregulation in monosodium iodoacetate (MIA)-induced KOA pain in rats. Materials and methods: Sprague-Dawley rats were divided randomly into three groups: Saline + Sham Laser, MIA + Laser, and MIA + Sham Laser. A 10.6 μm laser was used to irradiate ST35 (Dubi) for 10 min once every 2 days for a total of seven applications. The paw withdrawal mechanical threshold and weight-bearing distribution were performed to evaluate the nociceptive behaviors. Spinal expressions of microglial marker, ionized calcium binding adaptor molecule-1 (Iba-1); astrocyte marker, glial fibrillary acidic protein (GFAP); pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured 14 days after MIA injection. Results: The results showed that laser moxibustion significantly reversed the MIA-induced mechanical hyperalgesia and weight-bearing difference up to 14 days compared with MIA + Sham Laser group (p < 0.05 or p < 0.01). Moreover, both the protein level and immunofluorescence intensity of Iba-1 in the ipsilateral spinal cord dorsal horn were markedly decreased in the MIA + Laser group than those in the MIA + Sham Laser group (p < 0.01). However, there was no significant difference in the expression of GFAP between groups (p > 0.05). In addition, laser moxibustion decreased the upregulation of TNF-α, IL-1β, and IL-6 compared with the MIA + Sham Laser group (p < 0.01). Conclusions: This study demonstrated that laser moxibustion at ST35 significantly alleviated MIA-induced KOA pain through inhibition of the microglial activation-mediated neuroinflammation, at least partially, by suppressing the production of proinflammatory cytokines, which may provide a potential analgesic target for KOA pain relief.
Keywords: glial activation; knee osteoarthritis pain; laser moxibustion; neuroinflammation.