| Objectives: In order to explore the mechanism of repetitive transcranial magnetic stimulation (rTMS) on chronic neuropathic pain, we observe the effects of different frequencies of rTMS on chronic neuropathic pain and the expression of neuronal nitric oxide synthase (nNOS) in the dorsal root ganglion (DRG) and specific activation markers of astrocytes, glial fibrillary acidic protein (GFAP) in the lumbar spinal cord.Methods: Chronic constriction nerve injury induced by sciatic nerve ligation was used to model the chronic neuropathic pain. A total of 28 male Sprague-Dawley rats were used and divided into a sham-operated group and an operated group which in turn were divided into a sham-rTMS group, an 1Hz group, a 20Hz group after successful neuropathic pain model was established by operation, with 7 rats in each group. Three days after the operation, rTMS was applied to the primary motor cortex (M1) contralateral to the pain once daily for 10 consecutive days. Behavioral tests including behavioral observation, mechanical pain and heat pain responses were examined before and 3 days after injury and after rTMS therapy. By using immunohistochchemical technique , the expression of nNOS and GFAP were examined in DRG and lumbar spinal cord, respectively.Results: All the neuropathic pain model rats demonstrated pain-related behaviors 3 days postoperation, the mechanical pain threshold and thermal pain threshold were significantly lower than those in the sham-operated group (P<0.05). After rTMS treatment, the mechanical hyperalgsia and thermal hyperalgsia were significantly relieved in 20 Hz group but not 1Hz group as revealed by a comparison with the sham-rTMS group (P<0.05). Immunohistochchemical observation demonstrated that the expression of nNOS in DRG and GFAP in lumbar spinal dorsal horn ipsilateral to the neuropathic pain were significantly increased in sham-rTMS group and 1Hz group(P<0.05) when comnpared with the sham-operated group. When compared with sham rTMS group, the expression of nNOS in DRG and GFAP in lumbar spinal dorsal horn ipsilateral to the pain were significantly increased in 20 Hz group but not 1Hz group(P<0.05). The degree of pain relief in 20 Hz group and the expression of nNOS in corresponding DRG and GFAP in lumbar spinal cord ipsilateral to the neuropathic pain has a significant correlation.Conclusions: It is suggested that neuropathic pain induced by peripheral nerve injury is associated with elevated expression of nNOS in the DRG and increased activity and proliferation of astrocytes in spinal dorsal horn. High-frequency rTMS can relieve neuropathic pain through down-regulating the overexpression of nNOS in the DRG and inhibiting the activity and proliferation of astrocytes in spinal dorsal horn, but the low-frequency rTMS has no effect on neuropathic pain. |
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