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Cytoskeleton participation on crotalfine-induced antinociception in inflammatory pain.

Zanchetta LM1, Almeida AC1, Gutierrez VP1, Zambelli VO1, Picolo G1, Vessoni SS2, Santos MF3, Cury Y1

1 Laboratório Especial de Dor e Sinalização, 2 Laboratório de Fisiopatologia, Instituto Butantan, Brasil; 3 Instituto de Ciências Biomédicas, Universidade de São Paulo

Introduction: Crotalphine, a peptide first identified and isolated from Crotalus durissus terrificus snake venom presents a potent and long lasting antinociceptive effect. This effect is more prominent in the presence of tissue sensitization and involves the activation of cannabinoid CB2 and d- and k-opioid receptors and opening of ATP-sensitive K+ channels.  Objectives: In this study, we explored the cytoskeleton importance on crotalphine antinociceptive effect in an inflammatory pain model primed by PGE2. 

  Methods: Crotalphine effects on opioid receptors expression, endogenous opioids peptides release, cytoskeleton morphological reorganization and dendritic spines retraction were analysed in vitro using primary neurons isolated from DRGs. Pharmacological depolymerisation of cytoskeleton components prevented the antinociceptive effect of crotalphine. Gene expression of cytoskeleton regulators was evaluated by RT-PCR arrays and analysed by bioinformatics.  Results and Discussion: Cytoskeleton inhibition interferes with the effect of crotalphine by increasing the expression of δ opioid receptors (100% increase) and reducing the release of dynorphin A (80% decrease). Our results point out to the possible participation of the c-Jun N-terminal kinase (JNK) pathway in the antinociceptive effects of crotalphine. The herein described effects of cytoskeleton disruptors in the crotalphine antinociceptive effect form a body of evidence that further reinforce the importance of the cytoskeleton homeostasis as an essential player in the effect of crotalphine as a sensory neurons antinociceptive drug option in future pain management strategies. 

Supported by FAPESP
CEUAIB 855/11

3 - PHARMACOLOGY 21th Annual Scientific Meeting of Instituto Butantan.