Animal Venom Peptides Cause Antinociceptive Effects by Voltage-gated Calcium Channels Activity Blockage

Abstract

: Pain is a complex phenomenon that is usually unpleasant and aversive. It can range widely in intensity, quality, and duration and has diverse pathophysiologic mechanisms and meanings. Voltage-gated sodium and calcium channels are essential to transmitting painful stimuli from the periphery until the dorsal horn of the spinal cord. Thus, blocking voltage-gated calcium channels (VGCCs) can effectively control pain refractory to treatments currently used in the clinic, such as cancer and neuropathic pain. VGCCs blockers isolated of cobra Naja naja kaouthia (α-cobratoxin), spider Agelenopsis aperta (ω-Agatoxin IVA), spider Phoneutria nigriventer (PhTx3.3, PhTx3.4, PhTx3.5, PhTx3.6), spider Hysterocrates gigas (SNX-482), cone snails Conus geographus (GVIA), Conus magnus (MVIIA or ziconotide), Conus catus (CVID, CVIE and CVIF), Conus striatus (SO-3), Conus fulmen (FVIA), Conus moncuri (MoVIA and MoVIB), Conus regularis (RsXXIVA), Conus eburneus (Eu1.6), Conus victoriae (Vc1.1.), Conus regius (RgIA), and spider Ornithoctonus huwena (huwentoxin-I and huwentoxin-XVI) venoms caused antinociceptive effects in different acute and chronic pain models. Currently, ziconotide is the only clinical used N-type VGCCs blocker peptide for chronic intractable pain. However, ziconotide causes different adverse effects. The intrathecal route of administration also impairs its use in a more significant number of patients. In this sense, peptides isolated from animal venoms or their synthetic forms that modulate or block VGCCs channels seem to be a relevant prototype for developing new analgesics efficacious and well tolerated by patients.

PYCR in Kidney Renal Papillary Cell Carcinoma: Expression, Prognosis, Gene Regulation Network, and Regulation Targets

“…We found that the molecular functions of PYCR1 and its neighboring genes were tumor-associated voltage-gated calcium channel activity, phospholipid binding, and ubiquitin-like protein ligase binding. For instance, the voltage-gated calcium channel is closely related to cancer pain and inhibiting its activity can reduce cancer pain [22]. In addition, inhibition of T-type voltage-gated calcium channels showed antiproliferative and cytotoxic effects and is an important anticancer target [23].…”

A comprehensive review on ziconotide

“…In 2004, a pivotal event occurred with the FDA's approval of the first peptide toxin agent, ziconotide, marking a turning point in the field of analgesics, which led to a shift in research focus and sustained interest in exploring and discovering new analgesics derived from natural sources or synthesized compounds that modulate or block pain-associated ion channels [ 136 , 137 ]. Peptides derived from animal venoms, including those from cobras, cone snails, and spiders, can modulate or block voltage-gated calcium channels, leading to antinociceptive effects in various pain models, such as acute, inflammatory, neuropathic, postoperative, facial, visceral, and cancer-related pain [ 2 , 137 ].…”

“…Pain is a common reason for seeking medical attention [ 1 , 2 ]. It profoundly impacts individuals' quality of life and places a considerable social and economic burden on societies worldwide [ [2] , [3] , [4] , [5] , [6] ].…”

“…It profoundly impacts individuals' quality of life and places a considerable social and economic burden on societies worldwide [ [2] , [3] , [4] , [5] , [6] ]. It is categorized based on its duration, with acute pain having a short-term nature and often being linked to known causes, such as exposure to heat, extreme cold, chemical irritants [ 7 ], and chronic pain which persists or recurs for a minimum of three months [ 2 , [8] , [9] , [10] ], affecting approximately 20 % of the global population [ 2 , 11 ]. Chronic pain's development and progression are influenced by various factors, and among these, cancer pain continues to represent a significant portion [ 12 , 13 ].…”

Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications

“…For example, voltage-gated calcium channels are important for the process that conducts pain signals from the periphery into the dorsal horn of the spinal cord. Some conditions of pain that are difficult to treat with clinically available drugs, such as cancer and neuropathic pain, can be treated effectively with crotoxin [ 272 ].…”