Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesic effect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG Ια and PKG Iβ) of spinal cord were analyzed by RT-PCR. There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. Treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG Ια and PKG Iβ in the spinal cord. The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain.
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