Nociceptors use multiple neurotransmitters to drive pain
MacDonald, D. I.; Balaji, R.; Chesler, A.
10.1101/2025.09.09.675093 bioRxivShow abstract
Nociceptors are excitatory neurons that express a range of neuropeptides and have the essential role of detecting noxious mechanical, thermal and chemical stimuli. Ablating these neurons profoundly reduces responses to pain. Here we investigated how nociceptive information is transmitted by developing genetic approaches to suppress glutamate transmission and neuropeptide signaling, individually and in combination. Remarkably, many pain responses persisted in mice where either nociceptor glutamate or neuropeptide signaling was blocked. By contrast, mice lacking both glutamate and neuropeptide transmission in nociceptors displayed profound pain insensitivity closely matching the effects of cell ablation. Together our results establish a role for neuropeptides as bone fide pain transmitters and demonstrate redundancy in nociceptor signaling, resolving long-standing questions about how pain is communicated to the brain.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Opioidergic activation of descending pain inhibitory system underlies placebo analgesia 96%
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation 96%
- ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain 95%
Similar papers in this journal
- MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel 96%
- The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States 96%
- Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV+ interneurons 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.