The Holy Grail of modern pain medicine has always been the same: achieving the analgesic power of morphine without its side effects such as respiratory depression, addiction or tolerance. And although until now it seemed impossible, one study has suggested that the key is not to ‘numb’ the body, but to ‘attack’ the way the brain processes suffering.
The study. A team led by Gregory Corder of the University of Pennsylvania has developed a gene therapy that acts as a “switch” for chronic pain.
What is revolutionary is not just that it works, but how it does it: it eliminates the emotional distress of pain without erasing the protective physical sensation, keeping the patient safe but free from suffering.
The problem is not feeling, it is suffering. Pain has two very clear components: one that is sensory, which is necessary to human survival (as it is to withdraw the hand when we get burned), and the other is the affective or the emotional. This second is what generates the feeling of constant suffering that can destroy the quality of life of a patient who lives with chronic pain or neuropathic pain that affects the nervous system, such as the hated ‘sciatica’.
According to the study, titled, the researchers identified a specific group of neurons in the anterior cingulate cortex (ACC). These neurons are sensitive to opioids and are responsible for encoding the “unpleasantness” of pain, and this is where they have tried to attack, but surgically and without pills.
The tool used. The scientists used a tool known as DREADD (Designer Receptors Activated Exclusively by Designer Drugs). To do this, through a viral vector, they inserted synthetic receptors specifically into the cingulate cortex neurons of mice with neuropathic pain.
From there, they administered a drug that has no effect called DCZ. This compound, despite not doing anything to the body in mice, acts as a key that “turns off” the neurons that have been modified in their brain in a very specific way.
The result. The chronic pain behavior disappeared and they began to act like completely healthy animals. However, when exposed to an acute thermal stimulus, they were able to withdraw their paw. In this way, his survival system was working, but his anxiety system was completely turned off.
The AI that reads pain. One of the biggest challenges in pain research is that mice can’t tell us “it hurts a 7 out of 10,” which is why scientists classically relied on biased tests. But this is over thanks to an AI called LUPEwhich is a Deep Learning platform and has the ability to analyze hundreds of hours of video of mice moving freely.
But what is relevant here is that it has the ability to detect spontaneous micro-behaviors associated with pain that the human eye would miss. Thanks to LUPE, the team was able to objectively confirm that the pain relief was real and not an error of human interpretation.
The opioid crisis. The most promising thing about the study published a few days ago is the security profile. Unlike morphine, which generates tolerance, that is, more and more doses of medication are needed to have an effect, and addiction, this gene therapy is completely the opposite.
In this way, it does not generate addiction, meaning that the mouse does not have to seek a higher dose to maintain that sensation and the effect remained stable.
The arrival of humans. Although the success in mice is resounding, the jump to humans is complex, since we are really different and requires many more safety studies. However, the path is set. The team is already planning the next steps towards clinical trials, although it is something that may take many years to become a reality in our daily lives.
Images | Sasun Bughdaryan
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