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Our previous work has shown that somatostatin effectively inhibits neuropathic pain by activating its type 2 receptor (SSTR2) in the dorsal root ganglion (DRG) and spinal cord of mice. However, the underlying mechanism of this activation has not been elucidated.To explore further mechanisms, we examined pain behavior and the expression of neuropeptides such as calcitonin gene-related peptide (CGRP) in dorsal root ganglion neurons(DRGs) as well as the changes of the number of CGRP-IR DRGs in the mouse model of sciatic pinch nerve injury.In this model, the number of medium and small DRG neurons in ipsilateral CGRP-IR was slightly increased, but not significantly, compared with sham animals at 3, 7, and 9 days after pinch nerve injury. This correlated with the behavioral readouts of hypersensitivity at the same time points. However, the magnitude of the painful behavior (Autotomy) was observed after application of SSTR2 antagonist (CYN154806, 5 mg/kg) in the injured nerve groups compared to the saline-treated injured group as well as the sham-operated group. Following pinch nerve injury, there was a significant decrease in the number of ipsilateral CGRP-IR small and medium DRG neurons in SSTR2 antagonist (anti-SSTR2)- but not saline-treated mice. These data also correlated with painful behavioral readouts where hypersensitivity was significantly increased by anti-SSTR2 but not saline treatment.In all, application of the SSTR2 antagonist to the pinched sciatic nerve suppressed CGRP expression and aggravated painful behavior, suggesting that CGRP expression in DRG neurons can be an important component of the pain mechanism and an indicator of pain behavior. |
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