A TRPV1 positive allosteric modulator for chronic pain

An engineered synthetic form of the peptide venom toxin RhTx that acts as a positive allosteric modulator (PAM) of the ion channel TRPV1 could help treat chronic pain by inducing long-lasting analgesia, without the side effect of hyperthermia.

Structure-guided design of a folded peptidic PAM based on RhTx to selectively potentiate TRPV1 activation and delay TRPV1 desensitization yielded a compound that increased the effect of TRPV1 agonists such as capsaicin in causing calcium overload and promoted reversible degeneration of pain-sensing intra-epidermal nerve fiber-expressing TRPV1 channels, without changing the channel's heat activation threshold...