A optogenetics method that may be used to treat chronic pain

When your finger prick from a thorn, an immediate sensory response happened. Neurons at the injury site send an electrical signal to the central nervous system along the nerve fiber in that moment. Then your brain reminds you to keep away from the thorns and the feelings of pain subsides. However, some chronic and debilitating pain, causing by some health conditions, may derive from organs deep inside the body and may affect the body function. A long course of medicine to treat the discomfort could have undesirable side effects, such as drug dependency.

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Those affected experience abdominal discomfort that increases as their bladder fills, which in turn causes excessive urinary urgency and frequency. A research reported the first use of optogenetics to reduce bladder pain. The results in mice suggest that selective optogenetic silencing of nociceptive bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain.

Researchers performed the tests with mice bred with light-sensitive opsin proteins expressed in pain-sensing neurons. They also implanted some mice with small, flexible, light-emitting diode (LED) devices that are wirelessly controlled. By flipping the on-switch of the LED, they activated the opsin, which silenced the neuronal signal, resulting in pain relief for the animals. In the present study, the researchers tested whether a similar optogenetic system could be used to control neurons deep inside the body, with mice affected by bladder pain.

Robert W. Gereau IV, one of authors of this article, whose team studies the cellular and molecular mechanisms of chronic pain and collaborates with clinicians whose patients are affected by the disorder. One prevailing hypotheses of Urologists is that this problem is largely a dysfunction of the nervous system. This optogenetic approach could be a drug-free way to do a local nerve block coming from the bladder.

The team of Professor John A. Rogers designed the implanted LED devices used in the study. The miniaturized, wirelessly powered implantable devices are flexible and stretchable, so they do not impede the animals' movement, enabling stable operation in the animal, without any measurable adverse effects over many months.

Researchers performed three tests in mice. In the first, they recorded electronic signals of abdominal-muscle response during a procedure to fill the bladder, including normal mice and mice bred with the light-sensitive opsin gene. When LED light from a fiber-optic cable illuminated the bladder, the electronic signal measurements showed that genetically modified mice received pain relief during light exposure.
The second time, they performed a test to measure referred pain, in which the pain is felt at a location different from the original site of the stimulus. In this case, the pain from the bladder is felt in the abdomen wall. In this test, animals with the opsin protein received total reversal of referred pain. Then they continue to determine whether mice with bladder pain would respond to pain relief from the activation of a wireless LED implant. Mice is placed in a v-shaped maze, where they can move freely, and their movements are recorded. Results find that they like to hide in the corners of these things.



Another set of mice experiencing bladder pain are tested. Those without a light-sensitive opsin protein found a random corner to huddle. But those with the light-sensitive opsin protein and an implanted LED preferred the end of the maze at which researchers wirelessly activated the LED. It is the first time to demonstrate that an animal has ongoing pain that they are able to relieve on a moment-by-moment basis.

Significant challenges in gene therapy would need to be overcome if the approach is applied to human chronic pain eventually, but the hardware could be ready very soon. Implantable stimulators are already used to treat neurologic conditions, and scientists are trying to come up with safe, non-addictive ways to treat pain. It is imagined that patients could use a smart-phone app to adjust activation of implanted LEDs to regulate their chronic pain.

Source: https://www.nibib.nih.gov/news-events/newsroom/turning-light-switch-treat-chronic-pain

Article: Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain.

Authors: Samineni VK Mickle AD, Yoon J, Grajales-Reyes JG, Pullen MY, Crawford KE, Noh KN, Gereau GB, Vogt SK, Lai HH, Rogers JA, Gereau RW 4th.