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The use of toxins as novel molecular probes to study the structure-function relationship of ion-channels and receptors as well as potential therapeutics in the treatment of wide variety of diseases is well documented. The high specificity and selectivity of these toxins have attracted a great deal of interest as candidates for drug development. This review highlights the involvement of the proteins and peptide toxins as well as non-proteinaceous compounds derived from both venomous and non-venomous animals, in anti-nociception and anti-inflammation. The possible mechanisms of these potential therapeutic agents and possible clinical applications in the treatment of pain and inflammation are also summarized.

cDNAs encoding three phospholipase A2 (PLA2) isoforms in Naja naja sputatrix were cloned and characterized. One of them encoded an acidic PLA2 (APLA) while the others encoded neutral PLA2 (NPLA-1 and NPLA-2). The specific characteristics of APLA and NPLA were attributed to mutations at nt139 and nt328 from G to C and G to A, respectively, resulting in amino acid substitutions from Asp20 and 83 in APLA to His20 and Asn83 in NPLA. Amino acid sequencing of purified protein also showed the presence of this Asp20 and His20 in APLA and NPLA, respectively. The cDNA encoding one of the PLA2 (NAJPLA-2A), when expressed in Escherichia coli, yielded a protein that exhibited PLA2 activity.

The in vivo interactions between alpha-neurotoxin, cardiotoxin and two phospholipases A2 (sputa-phospholipase A2-1 and 3) isolated from Malayan cobra venom were assessed by examining the effects of simultaneous injection of sub-LD50 dose of one toxin on (i) i.v. LD50 S of the other toxins in mice; and (ii) mean survival times of mice injected with lethal doses of the other toxins. While LD50 measurements did not reveal any interaction between the toxins in vivo, survival time measurements suggest a synergy between the neurotoxin and sputa-phospholipase A2-1 and between sputa-phospholipase A2-1 and sputa-phospholipase A2-3. Our results also suggest that both sputa-phospholipases A2 interfere with the lethal action of the cardiotoxin, resulting in prolongation of the mean survival time of mice injected with a lethal dose of cardiotoxin. The patterns of in vivo interactions between phospholipase A2 and other venom toxins appear to depend on the nature and mode of pharmacological action of the phospholipase A2.