Abstract
Syb-prII, a recombinant neurotoxic polypeptide, has analgesic effects with medicinal value. Previous experiments indicated that Syb-prII displayed strong analgesic activities. Therefore, a series of in vivo and vitro experiments were designed to investigate the analgesic and anti-inflammatory properties and possible mechanisms of Syb-prII. The results showed that administered Syb-prII-1 and Syb-prII-2 (0.5, 1, 2.0 mg/kg, i.v.) to mice significantly reduced the time of licking, biting, or flicking of paws in two phases in formalin-induced inflammatory nociception. Syb-prII-1 inhibited xylene-induced auricular swelling in a dose-dependent manner. The inhibitory effect of 2.0 mg/kg Syb-prII-1 on the ear swelling model was comparable to that of 200 mg/kg aspirin. In addition, the ELISA and Western blot analysis suggested that Syb-prII-1 and Syb-prII-2 may exert an analgesic effect by inhibiting the expression of Nav1.8 and the phosphorylation of ERK, JNK, and P38. Syb-prII-1 markedly suppressed the expression of IL-1β, IL-6, and TNF-α of mice in formalin-induced inflammatory nociception. We used the patch-clamp technique and investigated the effect of Syb-prII-1 on TTX-resistant sodium channel currents in acutely isolated rat DRG neurons. The results showed that Syb-prII-1 can significantly down regulate TTX-resistant sodium channel currents. In conclusion, Syb-prII mutants may alleviate inflammatory pain by significantly inhibiting the expression of Nav1.8, mediated by the phosphorylation of MAPKs and significant inhibition of TTX-resistant sodium channel currents.
Highlights
The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensation and emotional experience associated with substantial or potential tissue damage [1]
SDS–PAGE analysis indicated the eluates containing target protein eluted with buffer C (Figure 2B, elution fraction C peak), that the eluates containing target protein eluted with buffer C
Syb-prII-1 could inhibit the expression of in a dose manner, especially at the pain, we explored the mechanism of the underlying therapeutic effect of Syb-prII-1/2
Summary
The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensation and emotional experience associated with substantial or potential tissue damage [1]. Pain is classified in two types: nociceptive pain and pathological pain [2]. Nociceptive pain is caused by intense irritation to evoke the sensation of pain and comes after direct tissue damage. Pathological pain, which may have somatic symptoms such as in sensory hypersensitivity and persistent pain, is divided into inflammatory pain and neuropathic pain. Neuropathic pain is defined as pain directly caused by damage or disease of the somatosensory system, including peripheral fibers (Aα, Aδ, and C fibers) and central neurons [3,4].
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