A tarantula peptide against pain via ASIC1a channels and opioid mechanisms

Abstract

Psalmotoxin 1, a peptide extracted from the South American tarantula Psalmopoeus cambridgei, has very potent analgesic properties against thermal, mechanical, chemical, inflammatory and neuropathic pain in rodents. It exerts its action by blocking acid-sensing ion channel 1a, and this blockade results in an activation of the endogenous enkephalin pathway. The analgesic properties of the peptide are suppressed by antagonists of the mu and delta-opioid receptors and are lost in Penk1-/- mice.

Upregulation of Acid-Sensing Ion Channel ASIC1a in Spinal Dorsal Horn Neurons Contributes to Inflammatory Pain Hypersensitivity

“…Although we demonstrate that ASIC1a channels in SDH neurons contribute to inflammatory pain hypersensitivity, we cannot rule out the involvement of ASIC1a in neuropathic pain models. In fact, previous evidence suggests a role of ASIC1a channels in neuropathic pain (Poirot et al, 2006;Mazzuca et al, 2007).…”

Independent Contribution of Extracellular Proton Binding Sites to ASIC1a Activation

“…There is growing interest in ASICs as potential therapeutic targets since they contribute to axonal degeneration in experimental autoimmune encephalomyelitis (23), neuronal damage in brain ischemia (24), pain sensation (4,6), and cardiac pain in myocardial ischemia (25,26). The findings reported here are particularly relevant to understand the process of activation as well as to develop inhibitors that target the gating machinery of these channels.…”

Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1

“…Among the ASICs, ASIC1 channels are responsible for transient, H + -evoked currents in neurons of the central nervous system and are involved in the physiological processes of learning and sensory perception such as pain 3,4 . Moreover, high levels of ASIC1 are located in the amygdala of mice suggesting a contribution to behavioural disorders including anxiety and depression 5 -7 .…”