By simulating the human pain-sensing neural system in a lab dish, Stanford researchers have accomplished a ground-breaking milestone that will provide previously unheard-of possibilities for the study and treatment of chronic pain, the scientists created four unique neural organoids that represented important areas of the ascending sensory pathway, including the thalamus, dorsal spinal cord, dorsal root ganglion, and somatosensory cortex, using skin cells that had been transformed into induced pluripotent stem cells, together these organoids created a 0.4-inch-long, three-dimensional "assembloid" with about 4 million cells that self-organized to create functional connections that mirrored the body's pain-signaling system, this is the first time that researchers have used cells that are solely generated from humans to replicate the full route, from peripheral feeling to brain processing.
When exposed to capsaicin, the substance that gives chili peppers their spiciness, the assembloid showed impressive capability, the chemical replicated the way pain signals travel through the nervous system by causing synchronized neuronal activity across the interconnected organoids, the construct's ability to transmit pain-related information was confirmed by researchers who saw wavelike electrical patterns passing through it, this innovation makes it possible to observe the transmission of pain signals in real time, which is a substantial improvement over conventional animal models whose neural pathways are very different from those of humans.
In order to model hereditary pain diseases, CRISPR gene editing technology was essential, scientists noticed hyperactive signaling patterns in the assembloid by inserting mutations in the SCN9A gene, which codes for the Nav1.7 sodium channel protein associated with hereditary pain syndromes, they were able to demonstrate the model's usefulness for researching genetic factors to chronic pain by simulating illnesses such as erythromelalgia, where Nav1.7 mutations produce excessive pain sensitivity, the CRISPR trials expand on previous research demonstrating the technology's potential for studying pain such as, recent studies that used it to target genes linked to pain in models of disc degeneration.
The model provides human-specific brain circuitry for testing, filling a major gap in pain research, as Dr. Sergiu Pasca points out, "Their pain pathways are in some respects different from ours... Our dish-based construct doesn't [experience pain]" highlights the drawbacks of the current reliance on animal models, the human-derived assembloid more accurately captures the intricacy of pain processing involving several brain regions, which combines with this ethical benefit to increase scientific relevance, the construct is perfect for mechanistic research because, although it emits signals, it is unconscious and does not "feel" pain, according to researchers.
The development of treatments for chronic pain may be completely transformed by this invention, from peripheral nerves to cerebral processing, the assembloid enables the methodical testing of possible treatments along the whole pain pathway it might be used by pharmaceutical companies to screen medications for toxicity and efficacy prior to human trials, which could speed up the discovery process, personalized approaches are also made possible by the model, which uses cells from individuals with particular pain problems to make customized assembloids for testing customized medicines.
Over 20% of persons worldwide suffer from chronic pain, and current medications are frequently ineffective or addictive, this is when the Stanford discovery was made, targeted treatments that prevent systemic side effects may result from this model mapping of the propagation of pain signals and identification of intervention choke points, the assembloid platform provides opportunities for both genetic and pharmacological therapies, in addition to the precision-editing capabilities of CRISPR, which have been shown in recent disc degeneration research, although clinical implementations are still years away, this human-specific model marks a significant advancement in our knowledge of pain mechanisms and the creation of safer, more efficient therapies.
When exposed to capsaicin, the substance that gives chili peppers their spiciness, the assembloid showed impressive capability, the chemical replicated the way pain signals travel through the nervous system by causing synchronized neuronal activity across the interconnected organoids, the construct's ability to transmit pain-related information was confirmed by researchers who saw wavelike electrical patterns passing through it, this innovation makes it possible to observe the transmission of pain signals in real time, which is a substantial improvement over conventional animal models whose neural pathways are very different from those of humans.
In order to model hereditary pain diseases, CRISPR gene editing technology was essential, scientists noticed hyperactive signaling patterns in the assembloid by inserting mutations in the SCN9A gene, which codes for the Nav1.7 sodium channel protein associated with hereditary pain syndromes, they were able to demonstrate the model's usefulness for researching genetic factors to chronic pain by simulating illnesses such as erythromelalgia, where Nav1.7 mutations produce excessive pain sensitivity, the CRISPR trials expand on previous research demonstrating the technology's potential for studying pain such as, recent studies that used it to target genes linked to pain in models of disc degeneration.
The model provides human-specific brain circuitry for testing, filling a major gap in pain research, as Dr. Sergiu Pasca points out, "Their pain pathways are in some respects different from ours... Our dish-based construct doesn't [experience pain]" highlights the drawbacks of the current reliance on animal models, the human-derived assembloid more accurately captures the intricacy of pain processing involving several brain regions, which combines with this ethical benefit to increase scientific relevance, the construct is perfect for mechanistic research because, although it emits signals, it is unconscious and does not "feel" pain, according to researchers.
The development of treatments for chronic pain may be completely transformed by this invention, from peripheral nerves to cerebral processing, the assembloid enables the methodical testing of possible treatments along the whole pain pathway it might be used by pharmaceutical companies to screen medications for toxicity and efficacy prior to human trials, which could speed up the discovery process, personalized approaches are also made possible by the model, which uses cells from individuals with particular pain problems to make customized assembloids for testing customized medicines.
Over 20% of persons worldwide suffer from chronic pain, and current medications are frequently ineffective or addictive, this is when the Stanford discovery was made, targeted treatments that prevent systemic side effects may result from this model mapping of the propagation of pain signals and identification of intervention choke points, the assembloid platform provides opportunities for both genetic and pharmacological therapies, in addition to the precision-editing capabilities of CRISPR, which have been shown in recent disc degeneration research, although clinical implementations are still years away, this human-specific model marks a significant advancement in our knowledge of pain mechanisms and the creation of safer, more efficient therapies.
