Generally, spidey senses hint at brewing trouble. But if those spidey senses come from a certain African species of tarantula, they may hint at a whole new way of brewing pain.

Two venom toxins from the tarantula species Heteroscodra maculate cause piercing pain sensations by targeting an ion channel in neurons not previously linked to pain, researchers report in Nature. In further experiments in mice, researchers found that these specific ion channels may underlie chronic abdominal pain in patients suffering from irritable bowel syndrome.

The finding—if validated in human studies—may help scientists unravel the complexity of pain perceptions and point to new ways to block the debilitating sensation. More specifically, the data suggests that finding a drug that could block this ion channel “represents a novel therapeutic strategy for diminishing the chronic pain in IBS and perhaps other pain conditions associated with mechanical sensitization, including migraine headache,” the authors conclude.

Mechanical sensitization is just one way our nerve cells detect pain—the type of pain one might feel while being pinched, squeezed, or pierced with fangs. There’s also chemical pain, such as that from eating a spicy pepper or being exposed to chemical weapons; thermal pain, felt during exposure to extreme heat or cold; and polymodal pain, brought on by an intense mix of those other types.

Regardless of the type, nerve cells can detect and relay pain signals using a variety of ion channels, including ones called voltage-gated sodium (Nav) ion channels. Generally, ion channels control how ions flow into nerve cells, which can generate action potentials that determine when the nerve cells fire off electrical signals of pain. Previous research found that three Nav ion channels in particular seemed to be important in pain perception: Nav1.7, Nav1.8, and Nav1.9. But there are actually six other Nav channels that, to this point, didn't seem to play as big a role in pain—or a role at all.

One of those other channels is Nav1.1. In earlier studies, scientists found that mutations in this ion channel were linked to epilepsy, autism, and Alzheimer’s. Some studies have also linked Nav1.1 to migraines but not pain specifically.

That changed in the new study, led by researchers at the University of California, San Francisco, Johns Hopkins University, and the University of Queensland. While fishing through the venom of various spiders, scorpions, and centipedes for novel pain-inducing toxins, the researchers came up with two new ones that specifically target Nav1.1. They dubbed the toxins δ-theraphotoxin- Hm1a (Hm1a) and δ-theraphotoxin-Hm1b (Hm1b).

In mouse experiments, injections of either toxin into a paw caused the mice to lick and bite the afflicted tootsies—a behavioral response to pain. The researchers next ran experiments to figure out the flavor of pain—thermal or mechanical or so on—that the toxins were triggering via Nav1.1. By exposing the paws to heat and touch after the injection, the researchers found that the rodents’ paws were hypersensitive to touch but not heat. This suggests that by targeting Nav1.1, the toxin was messing up the signals for mechanical pain.

Though the finding is the first to point to Nav1.1 as having a role in pain, the researchers quickly drew a potential link to human health, namely to irritable bowel syndrome. Previous research had shown that some people with IBS are hypersensitive to mechanical pain in their abdomens and that this may play a role in chronic pain from the gut condition—perhaps Nav1.1 is involved, the researchers hypothesized.

Connecting the dots, the researchers found that there are in fact a lot of Nav1.1-expressing nerve cells in the gut. And when the researchers injected Hm1a into mice that have many of the same symptoms as people with irritable bowel syndrome, they found that the mice were hypersensitive to the toxin, meaning their Nav1.1-based pain signals were already out of whack. This suggests that flukes in this channel's activity may underlie the chronic discomfort of those with irritable bowel syndrome.

For now, the finding is only in mice, and it’s unclear if it will hold up in humans. Additionally, researchers still don’t know exactly how Nav1.1's potential role in mechanical pain might fit into its potential role in other conditions, such as epilepsy and migraines. Nevertheless, the researchers see the findings as motivation to keep sinking their teeth into Nav1.1.

Nature, 2016. DOI: 10.1038/nature17976 (About DOIs).