Nociceptive effect induced by phospholipase A2 (PLA2-Lys49 and PLA2-Asp49) isolated from Bothrops asper venom: characterization of central mechanisms and molecular determinants.

Author(s)

Marucia Chacur

• Document type: Doctoral Thesis
• Press: São Paulo. , ilustrações.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2004-11-22

Examining board members

Yara Cury; Edson Antunes; Paulo Sérgio Lacerda Beirão; Igor Dimitri Gama Duarte; Catarina de Fatima Pereira Teixeira

• Advisor: Yara Cury
• Field of knowledge: Biological Sciences - Pharmacology
• Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
• Location: Universidade de São Paulo. Biblioteca do Instituto de Ciências Biomédicas; ICB/T-ICB BMF QV4; C431e 2004

Abstract

Phospholipase A2 (Lys49, catalytically-inactive and Asp49, catalytically active), isolated from Bothrops asper snake venom, induce pain. The present studies examined the molecular, structural and central mechanisms involved in hypernociception induced by both PLA2s. These PLA2s induced mechanical hyperalgesia, whereas only PLA2-Lys49 evoked allodynia. The C-terminal region of the PLA2-Lys49 seems to be responsible for hyperalgesia, whereas the enzymatic activity of PLA2-Asp49 contributes to such an effect. Calcium and sodium channels are involved in PLA2s-induced hyperalgesia. In the spinal cord, NK1 and CGRP receptors, glutamate ionotropic receptors, NO, IL-1, prostanoids and adenosine contribute to hyperalgesia caused by PLA2s. Additionally, metabotropic glutamate receptors and TNF are involved in hyperalgesia induced by PLA2-Asp49. NK1, NK2 and CGRP receptors, glutamate receptors, TNF and prostanoids mediate allodynia. Activation of spinal astrocytes and microglia contribute to the generation of hyperalgesia and allodynia induced by both toxins. (AU)