The analgesic effect of early hyperbaric oxygen treatment in chronic constriction injury rats and its influence on nNOS and iNOS expression and inflammatory factor production

OBJECTIVE: To observe the analgesic effect of early hyperbaric oxygen (HBO) treatment in chronic constriction injury (CCI) rats, and to analyze the influence of HBO on the expression of neuronal nitric oxide synthase and inducible nitric oxide synthase and on the levels of inflammatory factors. METHODS: Rats were assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model was established, and HBO treatment at 2.5 ATA (60 min) was given one day after surgery, lasting for five consecutive days. The pain behaviors of the rats were observed at predetermined time points, and the activation of astrocytes at dorsal horns as well as the changes of the synaptic ultrastructures were observed. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were detected by Western blot, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were detected by quantitative real-time PCR. RESULTS: Rats in the CCI group developed hyperalgesia when compared with the sham group. Mechanical withdrawal threshold decreased and thermal withdrawal latency shortened in CCI group. Also, astrocytes at the dorsal horn were activated, the synaptic structure was disordered, the expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were increased significantly, and the release of inflammatory factor (TNF-α and IL-1β) was up-regulated. However, with early initiation of HBO treatment, rats in the HBO group showed significantly alleviated hyperalgesia, increased mechanical withdrawal threshold, and prolonged thermal withdrawal latency. HBO treatment inhibited astrocyte expression and maintained normal synaptic structure. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were decreased in the dorsal horn, and the release of inflammatory factor (TNF-α and IL-1β) was reduced. CONCLUSIONS: Early HBO treatment significantly improves hyperalgesia in rats with neuropathic pain. The decreased expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase and reduced levels of inflammatory factors are important mechanisms by which early HBO helps to alleviate neuropathic pain.