Pain-Causing Venom Peptides: Insights into Sensory Neuron Pharmacology

Abstract

Venoms are produced by a wide variety of species including spiders, scorpions, reptiles, cnidarians, and fish for the purpose of harming or incapacitating predators or prey. While some venoms are of relatively simple composition, many contain hundreds to thousands of individual components with distinct pharmacological activity. Pain-inducing or "algesic" venom compounds have proven invaluable to our understanding of how physiological nociceptive neural networks operate. In this review, we present an overview of some of the diverse nociceptive pathways that can be modulated by specific venom components to evoke pain.

Keywords: ASIC; TRP channel; animal venom; pain; pore forming toxin; sodium channel.

Figure 1

Pain due to envenomation typically occurs as a result of activation of nociceptive or “pain-sensing” peripheral nerve endings which express a host of ion channels and receptors that are targeted by venom components. Key molecular targets of algesic venom components include ASICs, TRPV1, TRPA1, Na_V and K_V channels. Activation of ASICs and TRPs contribute to generator potentials—small, graded depolarisation. K_V channels play key roles in setting the resting membrane potential, whilst once a threshold of membrane depolarisation has been reached, the opening of Na_V channels leads to the rapid upstroke of the action potential.