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Release: Oct. 2, 2001

UI studies advance understanding of common pain treatment

IOWA CITY, Iowa -- University of Iowa researchers are gaining a better understanding of how a common pain-relief therapy, used clinically for decades to treat chronic pain such as arthritis, low back pain, ankle injuries and muscle pain, works. Transcutaneous electrical nerve stimulation (TENS), which involves electrical stimulation of nerves through the skin, is non-invasive, inexpensive and safe. However, TENS is not universally accepted as an effective pain treatment.

"There is a lot of controversy about whether TENS works," said Kathleen Sluka, Ph.D., UI associate professor of physical therapy and rehabilitation sciences. "And, if it does work, it is not clear what type of pain it treats best or how long-lasting the effects are."

Sluka believes that much of the controversy stems from a lack of understanding of the basic science behind this technique and from the complicated nature of measuring pain and assessing pain relief. Sluka and her team decided to investigate in detail the effect of TENS on pain signaling pathways in animal models.

"By understanding the mechanisms of TENS we can utilize combinations of the stimulation with pharmaceutical agents to enhance pain relief and make this treatment more effective," Sluka said.

TENS equipment consists of electrodes, which attach to the skin, and a small battery-powered unit which controls the frequency, intensity and duration of the electrical stimulation. Patients can use this portable device to help them control pain and allow them to lead normal lives.

TENS stimulation can be applied at varying frequencies. The UI team studied the effects of low-frequency and high-frequency TENS on pain relief in animal models.

The team found that both low- and high-frequency stimulation inhibit pain sensitivity away from the site of an injury. However, only high frequency TENS has any effect on pain sensitivity at the site of injury and it is only a small effect. This finding suggests that how effective TENS is as a pain relieving therapy depends on the type of pain being targeted.

Proteins called opiate receptors control biochemical pathways that inhibit pain. These proteins interact with chemicals called opiates, and one consequence of this interaction is pain relief. It had been suggested that TENS might interact with opiate pathways.

Through their studies, Sluka and her colleagues discovered that both low-frequency and high-frequency TENS acts on this biochemical pathway.

Opiate drugs such as morphine are commonly used to treat pain. Sluka and her team wanted to know how TENS and opiates work together given that the evidence indicates that these two treatments work on the same pain-signaling pathways.

The UI researchers found that both low- and high-frequency TENS in combination with morphine produced greater pain relief than either TENS or the drug alone.

This means that by adding TENS to a treatment regime, one can lower the dose of opiates required to achieve adequate pain control, Sluka said. This is an advantage because these drugs have some undesirable side effects.

However, there are several different types of opiate receptor and the UI team also discovered that different frequencies of TENS selectively target different opiate receptors to produce pain relief.

Investigating the effect of TENS on animals that had developed a tolerance to morphine, the UI researchers found that low-frequency TENS no longer relieved the animals' sensitivity to pain, but high-frequency TENS still worked. This finding makes sense given the previous studies, which had shown that low-frequency TENS works on the same opiate receptor as morphine, whereas high-frequency TENS activates different opiate receptors.

Our research shows the importance of understanding which opiate receptors are activated by various treatments so that you can rationally combine treatments to optimize pain relief, Sluka said.

An understanding of how TENS affected the opiate pathway led to another discovery, which also could have implications for pain treatment.

Clonidine is a drug used to treat pain. It is not an opiate and produces pain relief by acting on a different kind of receptor. Previous studies had shown that if clonidine's receptor and opiate receptors are activated at the same time, then the pain-relieving effect is synergistic. In other words the combined effect is greater than the sum of the individual effects.

Sluka and her team found that low-frequency TENS and clonidine produced the greatest pain relief. This result was exciting, Sluka noted, because the experiments measured decreased pain sensitivity at the site of injury where TENS is usually not effective.

"Low-frequency TENS usually has no effect on pain sensitivity at the site of injury," Sluka said. "However, in combination with a really low dose of this drug, low-frequency TENS eliminated the increased sensitivity to pain at the injury site."

Sluka noted that future studies would be needed to determine whether her team's results from animal studies are mirrored by success in humans.

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