Low back pain is the most common form of chronic pain in people. Yet it’s difficult to model and study this condition in rodents to learn more about what causes the pain. But recently, scientists have found a way to overcome this hurdle—by setting their sights on the rat tail.
What could the tail of a rat teach anyone about low back pain in people? Quite a lot, it turns out.
Unlike people, a rat’s spine extends beyond the lower back and runs the entire length of the tail. So, two teams of scientists at the National University of Ireland Galway joined up to take a closer look.
The first team, led by pain researcher David Finn, experimentally damaged the spinal discs at the base of the tail. They did this to replicate what happens in a common form of back pain in people called discogenic low back pain, which occurs when the discs of the spine degenerate with age. For over a month after the injury, the rats experienced tail pain, which the researchers measured and assessed.
The second team, led by Abhay Pandit, developed a so-called “biomaterial” that, when implanted into the disc at the time of the experimental injury, prevented pain from developing in the first place. The researchers believe a similar treatment approach could one day help people with low back pain, though the current study is only a very early step towards that goal.
“If you look at the proportion of people with back pain versus other [forms of] chronic pain, and compare that to the minimal amount of preclinical [animal] work being done, there’s an immense mismatch,” explains Laura Stone, a researcher at McGill University in Montreal who studies low back pain but was not involved in the study. “A big reason for this is that we need to develop more animal models of low back pain, and so this paper nicely addresses that.”
The study appeared April 4, 2018 in the journal Science Advances.
A better way to study low back pain in animals
The spine consists of a repeating pattern of vertebrae and intervertebral discs. The discs act like shock absorbers and somewhat resemble a jelly donut, with a gel-like center and a fibrous exterior.
With age or injury, the discs degenerate and the gel-like center begins to leak out. But unlike a jelly donut, the gel inside the disc contains substances that cause pain.
“As the discs are breaking down, they are leaking and so this noxious content within the disc is more likely to escape and find contact with nerve fibers,” explains Stone.
Even worse is that the gel within the disc also contains substances that cause the nerves to grow into the disc, in a phenomenon called “hyperinnervation.”
“There aren’t supposed to be nerve fibers in the disc, but now the nerves that got into the disc are even further exposed to all that nasty stuff,” says Stone.
Some scientists have used rodents to study how the disc degenerates, but few have examined the pain it causes. This is a key issue, since, as Stone explains, “patients don’t really care if their discs are degenerating. They care if they have pain.”
But the problem is that injuring a disc in the back of a rat requires extensive surgery that by itself would cause pain. So instead, Finn’s team turned to the tail, which contains discs just like the back does, but are much easier to gain access to surgically.
“Humans don’t have a tail and we recognize that, but the discs in a rodent’s tail and fundamental pain mechanisms are not that much dissimilar, on an anatomical and physiological level, to humans,” says Finn. Pain mechanisms are the workings of the pain system at the cellular and molecular level.
When discs go bad, pain emerges
So Finn and his colleagues surgically punctured discs at the base of the tail and monitored the development of pain. They confirmed that the animals became sensitive both to pokes of the paw with a thin filament (a common procedure used to assess pain in animals) and to heat applied near the base of the tail. The pain lasted for over of a month.
“It’s a relatively straightforward surgery, yet it results in quite a persistent pain-like phenotype,” says Finn, referring to the observable behavior of the animals suggesting their discomfort.
The team then assessed the extent of damage to the discs and found changes to genes and proteins that confirmed extensive degeneration and inflammation of the discs.
With Finn’s group having shown it was possible to measure pain in the tail and that the pain lasted for a while, in stepped Pandit’s team, whose research focuses on the development of biomaterials for the treatment of numerous diseases. Biomaterials are designed to interact with biological systems to improve health after injury or disease.
They already knew that when discs degenerate, a substance in the disc called hyaluronic acid (HA), which is important for proper disc health, begins to degrade. This suggested a new treatment approach.
“We hypothesized that putting HA back into the disc could stop degeneration and reduce pain,” according to Finn.
So Pandit created a small, spherical “hydrogel” resembling a tablet that contained intact HA and implanted it into the disc at the time of the surgical puncture. As hoped for, the biomaterial prevented the development of pain and significantly reduced disc degeneration.
“It was the month-long duration [of pain relief] that was quite surprising,” says Finn. “It was a very pronounced and sustained effect.”
The new study is the first to characterize the course of pain in rats with injured tail discs. And it may encourage more researchers to study low back pain.
“Given the scale of the clinical problem,” says Finn, “more basic research on low back pain would be very welcome, and so perhaps this model will facilitate that.” Basic research refers to laboratory work with cells and animals.
But what about patients with low back pain? While the hydrogel relieved pain in the animals when the researchers implanted it at the time of disc injury, patients usually don’t see a doctor until their discs have already begun to degenerate.
“We see this as the first steps in fully fleshing out this model and treatment approach,” Finn says. “In future studies, we will explore implanting or injecting the hydrogel weeks after the injury and see if it can reverse [disc] degradation and pain.”
To read about the research in more detail, see the related IASP Pain Research Forum news story here.
Nathan Fried is a postdoctoral fellow at the University of Pennsylvania, Philadelphia, US.