Venom-Derived Peptides Inhibiting Voltage-Gated Sodium and Calcium Channels in Mammalian Sensory Neurons

Pain management is a serious worldwide problem that affects the physical and mental health of all affected humans. As an alternative to opioids, pharmaceutical companies are seeking other sources of potential analgesics that have fewer adverse side effects. Animal venoms are a natural cocktail of a complex mixture of salts, peptides, and proteins. Most animals that produce venoms release them for the purpose of prey capture and/or defense against other vertebrates. Over the last 30 years, many venom-derived peptides have been shown to be active against numerous voltage-gated ion channels in the mammalian somatosensory nervous system. Voltage-gated ion channels and in particular sodium, potassium, and calcium channels are fundamental to the transmission of all somatosensory information from the periphery to the central nervous system. This information can be chemical, mechanical, or thermal sensation that can result from touch to a more painful sensation of tissue injury. These voltage-gated ion channels open or close in response to changes in membrane potential to permit ion movement across the cell membrane. In this chapter, we screened the scientific literature characterizing venom-derived peptides that target voltage-gated sodium and calcium channels and exhibit analgesic properties. Depending on peptide activity, these can either inhibit voltage-gated sodium or calcium channels completely by binding to the pore of the channel or modulate the activity by binding to other regions such as the voltage sensor of the channel.