Abstract
Chronic pain is a major medical issue which reduces the quality of life of millions and inflicts a significant burden on health authorities worldwide. Currently, management of chronic pain includes first-line pharmacological therapies that are inadequately effective, as in just a portion of patients pain relief is obtained. Furthermore, most analgesics in use produce severe or intolerable adverse effects that impose dose restrictions and reduce compliance. As the majority of analgesic agents act on the central nervous system (CNS), it is possible that blocking pain at its source by targeting nociceptors would prove more efficient with minimal CNS-related side effects. The development of such analgesics requires the identification of appropriate molecular targets and thorough understanding of their structural and functional features. To this end, plant and animal toxins can be employed as they affect ion channels with high potency and selectivity. Moreover, elucidation of the toxin-bound ion channel structure could generate pharmacophores for rational drug design while favorable safety and analgesic profiles could highlight toxins as leads or even as valuable therapeutic compounds themselves. Here, we discuss the use of plant and animal toxins in the characterization of peripherally expressed ion channels which are implicated in pain.
Highlights
Pain is a physiologically important phenomenon as it alerts an organism to tissue damage or potential tissue damage [1]
BmP01 produce pain when injected to mice, these toxins present the possibility of developing Transient Receptor Potential Vanilloid 1 (TRPV1) modulators that produce fine-tuning of the channel activation by physiological stimuli
The authors suggested that the toxins produce the significant analgesic effect in vivo through desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor
Summary
Pain is a physiologically important phenomenon as it alerts an organism to tissue damage or potential tissue damage [1]. BmP01 produce pain when injected to mice, these toxins present the possibility of developing TRPV1 modulators that produce fine-tuning of the channel activation by physiological stimuli This may prove useful in evoking a desirable response while preventing unwanted side effects. TRPV1 activation by low concentrations of capsaicin and protons [90] Both toxins showed analgesic effects in acute and chronic pain models in mice without causing hyperthermia [55]. The authors suggested that the toxins produce the significant analgesic effect in vivo through desensitization of the TRPA1 receptor According to this hypothesis, Ms 9a-1 and Ueq 12-1 potentiate the response of TRPA1 to endogenous agonists, which results in weak but sustained activation of the receptor leading to functional loss of TRPA1-expressing neurons [144,157].
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