Popis: |
Chemotherapy-induced neuropathic pain (CINP) is intractable, and spinal cannabinoid receptors (CBRs) are potential therapeutic targets for CINP. Previous studies demonstrated that hyperbaric oxygen (HBO2) may contribute in alleviating specific peripheral neuropathic pain. However, neither CINP nor CBR have been clarified. We hypothesized that HBO2 is capable of alleviating CINP, and the effect could be explained by the activation of spinal CBRs.A series of paclitaxel-induced CINP models were established on male Sprague-Dawley rats. Then HBO2 treatment was administered for seven consecutive days at 2.5 atmospheres absolute. Two groups were treated with AM251 (an antagonist of CBR type-1, CBR1) or AM630 (an antagonist of CBR type-2, CBR2) respectively 30 minutes before each HBO2 treatment. The mechanical withdrawal threshold was assessed before, during and at two weeks after HBO2 treatment. Lumbar spinal cords were collected for Western blot analysis of CBR1, CBR2, GFAP and CD11b, and ELISA analysis of proinflammatory cytokines IL-1β and TNF-α.A mechanical allodynia was successfully exhibited and the spinal GFAP, CD11b, IL-1β and TNF-α significantly increased after the modeling, and these effects could be further reversed by HBO2 treatment, which could be blocked by AM630, other than AM251.HBO2 treatment can alleviate paclitaxel-induced neuropathic pain, and be mediated by CBR2. Spinal glial cells and proinflammatory cytokines are involved in this process. |