A research team at the Yonsei University College of Medicine has discovered the principle of modulating chronic neuropathic pain (NP) by applying electrical stimulation to the brain, Severance Hospital said Tuesday.
The research team, led by Professors Cha Myeoung-hoon and Lee Bae-hwan, found in animal testing that the number of astrocytes in the unconfirmed area (zona incerta) in cerebrum noticeably decrease in pain situation, and recovers to a normal level if given with electrical stimulation called the Motor Cortex Stimulation (MCS).
|Professors Lee Bae-hwan (left) and Cha Myeoung-hoon|
The result suggests the possibility of treating chronic NP by inducing changes in the synapse by artificial electrical stimulation. The modulation may apply to patients with chronic NP, who are unable to expect the effects of drugs.
Chronic pains are caused by a lesion in peripheral nerves, complex regional pain syndrome (CRPS), and cancer. Treating chronic NP with medications is less effective than expected, and even if they are effective, side effects make the treatment difficult to continue.
The research team sought to find a pain modulation method in neurological changes. Zona incerta in the cerebrum is a region whose role is unclear. According to previous studies, the neuronal activity level is significantly lower in zona incerta of subjects with chronic NP. The team hypothesized that recovering the neuronal activity level in zona incerta would revitalize the activity of zona incerta and eventually relieve pain.
The researchers inflicted nerve damage to rats in experimental groups (sky and blue color in the graphic) and gave false nerve damage to rats in the control group (red). The team measured the thresholds of pain in response to physical stimulation.
As shown on the left side of the chart, the experimental group with nerve damage tended to show a gradual decrease in the threshold for stimulation (pain increases). The team also found a significant difference compared to the control group with false nerve damage. The researchers measured change in pain by using repetitive MCS for 10 days.
As a result, the experimental group that received MCS showed a threshold value that increased to the same level as the control group (red) over time, which pointed to the absence of pain. In contrast, the experimental group showed no sign of change in threshold.
The researchers also observed changes in the brain in animal models that underwent MCS and found an activation of astrocyte, which recovered after decreasing in the zona incerta.
In the control group, green astrocyte expressed in the zona incerta (left image). However, the experimental group with nerve damage showed a decrease in astrocyte (center). After receiving repeated MCS Normal level of astrocyte was expressed.
"We think MCS not only reduced pain induced by nerve damage but also mediates synaptic changes and modulation of astrocyte in zona incerta," Professor Lee said. "Changing the brain's neuroplasticity is possible by artificial stimuli such as MCS, and it seems that the application of our findings can help pain control of chronic NP patients who are hard to cure."
Professor Cha pointed out that the possibility of controlling chronic NP by modulating neuronal synapse based on this study suggests excellent implications. He also said that clarifying the neuronal signal regulation between brain cells through follow-up studies can help understand the brain and provide efficient ways to control the pain modulation process.
The study titled the “Astroglial changes in the zona incerta in response to motor cortex stimulation in a rat model of chronic neuropathy,” was published in Scientific Reports, a sister journal of a global scientific journal, "Nature," on Jan 22.