Spider Toxin Rises to the Occasion, Making Pain Go Away

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When I think of spiders, I recall the movie Arachnophobia, in which those South American crawlers hitch a ride to America and kill unsuspecting folks.  Luckily, spiders, if they bite, don’t really feed on humans, but if they do it’s more for purposes of self-defense.

When a bite occurs, the venoms that are medically significant are those that can cause tissue necrosis, they contain neurotoxins or they cause the release of serotonin – a neurotransmitter. But not all spider venom is bad – in fact, it can be pretty great.

In a recent study published in the British Journal of Pharmacology, scientists have been able to synthesize a peptide molecule, PnPP-19, using a component of spider venom called PnTx2-6 as a model.

Previous research on PnTx2-6 revealed that this molecule had several different biological effects including inducing erections in male rats as well as causing a heightened sensitivity to pain (hyperalgesia) on a systemic level, not just at the site of injection.

The expectation when PnPP-19 was synthesized was that it would closely mimic the actions of PnTx2-6 – erections and pain. While being able to also induce erections in rats, they found that, in fact, the synthetic molecule blocked the sensation of pain in rats. How could this be?

When analyzed further, this particular molecule, PnPP-19, activated two different families of receptors (opioid and cannabinoid) that are involved in perceiving pain and inducing analgesia (absence of pain). Additionally, PnPP-19 was able to block the breakdown of the body’s innate pain-reliever, the endogenous opioid family known as enkephalins.

"Our findings reveal at least part of the mechanism of action underlying the pain relieving effects induced by PnPP-19," said Dr. Maria de Lima, lead author of the study in a press release. "They also may contribute to the consideration of PnPP-19 as a potential lead compound for the development of new drug candidates to treat pain."

The authors of this paper had built upon previous research which had shown that spider venom are toxins that act on many different targets.

Two toxins previously isolated had shown potential as drug sources for pain treatment: PnTx3-3 and PnTx3-6 where they similarly were able to induce an antinociceptive (inability to sense pain) effect but these are different from PnPP-19 in that they had not been capable of achieving pain relief by activating opioid and endocannabinoid receptors.

Interestingly, the authors also mention that sildenafil, commonly known as Viagra, also demonstrated the capacity to block pain sensation by activating the same opioid receptors as PnPP-19.

In 2014, the opioid addiction crisis affected 1.9 million Americans (not counting the 586,000 that have a use disorder involving heroin) and drug overdoses were the leading cause of accidental deaths, driven by the opioid addictions. It is therefore, welcome news to potentially have alternative options for people who require pain relief.