Twat, imbecile, troll, numbskull – the string of swear words we release when we stub a toe or touch a hot pan are all too familiar. What isn’t quite as clear cut are the pain pathways involved. Sure, there is the first stab of pain and then the lingering ache or sting of injury. However, much of the research doesn’t differentiate between these two sensations.

Now, a team of researchers suggest there is a previously unknown nerve pathway involved – one that could have implications for studies that investigate pain.

“When the first-line response fails to prevent tissue damage (for example, a finger is burnt), the resulting pain invokes a second-line coping response – such as licking the injured area to soothe suffering,” wrote the team in a paper published in Nature. “However, the underlying neural circuits that drive these two strings of behaviour remain poorly understood.”

To demystify this phenomenon, the team did what all good scientists do and tested their hypothesis. Previous work of theirs suggested that at least two groups of neurons are involved: ones that are close to the skin's surface and others that are deeper down in the tissue, bones, joints, and muscles. The first is involved in the reflex to notify us when something harmful is in our way, while the second results in damage that needs healing.

To delve further into this deeper damage, they bred mice to lack a specific spinal cord neuron called TAC1. Fortunately or unfortunately, depending on how you look at it, these mice reacted differently to pain than the control mice. When pricked or burned, they did indeed pull back their little paws. However, unlike the control mice, they did not nurse their wounds afterward – a marker the scientists used as the mice's attempt to soothe prolonged pain. 

“This coping response was greatly reduced in mice in which TAC1 neurons were ablated. However, top-down execution of the licking motor behaviour per se is not impaired; ablated mice retained their licking responses to intraplantar capsaicin [mustard oil] injection," the team wrote. "This last finding suggests the existence of pain pathways that are independent of TAC1 neurons.”

Okay, so they’ve found that TAC1 neurons are involved but they are not the sole player in the story. A deeper search found that TRPV1 neurons signal to TAC1 spinal cord neurons, which project to the base of the brain in the medial thalamic nucleus. 

The takeaway? Pain research is still more nascent than previously believed. What’s more, it’s possible that commonly used tests of pain in animal research only measure the superficial pain and not the ongoing pain later. 

This study, it should be noted, did not look into chronic pain (which likely complicates the picture even further). Instead, it looked into the lingering pain that occurs minutes post-injury. 

“I think it’s still a little too early to say that this is [the pathway] we need to be looking at” in the search for new drugs, said Gregory Dussor, a neurobiologist at the University of Texas in Dallas, to Science Magazine.

Additionally, “the vocabulary is limited for describing what a licking response might actually reflect,” said Kathryn Albers, a neurobiologist at the University of Pittsburgh in Pennsylvania. “‘Coping’ might be a stretch.”

Of course, this is the problem with all animal research: the critters can’t speak about their experience to researchers. Still, the discovery does provide a direction for future research and possibly even new pathways to target for painkillers.

[H/T: Science Magazine]