Short story:

• Sodium channel NaV1.7 is a powerful protein to control pain, as demonstrated by humans who can't feel any pain
• Blocking NaV1.7 in the sympathetic nervous system leads to side effects
• Targeting NaV1.7 selectively is very hard, sodium channels look alike
• Encoded has developed a treatment which knocks-down the gene coding for NaV1.7 in pain sensing neurons only, using viral delivery of miRNA

There are ever new ways to target proteins central to pain control, which can deliver both strong analgesia and fewer central side effects. The cool story here is just their technology and that we are seeing ever more ways of achieving it. The fact that private money is funding it is really good news. Even when these companies fail, the fact that the money is there to do the research means we are heading into new territory where a successful new pain therapy isn't decades away anymore.

Full paper: https://www.nature.com/articles/s41572-026-00741-7.epdf?sharing_token=uDMKTmvmeZmrmUKwtcfNbNRgN0jAjWel9jnR3ZoTv0NOueCKVhgknnNmNF6-Lw7-ps37W84ZHIaDcXePiND5_txcdwi0wst907LGtMLDLC8h5ckNMjemicCl6HJdI4mZQou0WM4Lb3pGe7oZxkRAKTI9vWcGV4uZ5gklswV-RJ8%3D

Abstract

Irritable bowel syndrome (IBS) is one of the most prevalent disorders of gut–brain interaction, characterized by recurrent abdominal pain or abdominal discomfort associated with altered bowel habits in the absence of identifiable structural disease. IBS affects ~4–11% of the global population and is associated with substantial healthcare utilization, impaired quality of life and considerable socioeconomic burden. IBS is increasingly recognized as a heterogeneous condition caused by dysregulated bidirectional communication within the gut–brain axis. Altered gastrointestinal motility, visceral hypersensitivity, epithelial barrier dysfunction, neuroimmune activation, gut microbiome and metabolome changes, central pain amplification, stress and autonomic dysregulation, and sex-related biological influences underlie pathophysiological mechanisms. IBS can develop after a gastrointestinal infection and can frequently co-occur with other disorders of gut–brain interaction, chronic pain conditions, psychological disorders and organic gastrointestinal disorders such as inflammatory bowel disease and coeliac disease. Diagnosis relies on a positive symptom-based approach using the Rome V criteria, supported by clinical assessment and limited testing to exclude differential diagnoses. Management focuses on improving symptoms and quality of life through an individualized, stepwise approach that involves patient education, dietary interventions, pharmacological therapies and gut–brain behaviour therapies. Emerging biomarkers, multi-omics approaches, digital health tools and precision medicine strategies may enable mechanism-based diagnosis and targeted treatment in the future.

Abstract

For decades, we have known that women, especially younger women, are disproportionately affected by pain disorders, including irritable bowel syndrome, endometriosis, menstrual migraines, fibromyalgia, osteoarthritis, and neuropathic pain, all of which degrade quality of life. The adoption of sex as a biological variable in 2016 has begun to transform the field, revealing distinct sex-specific pathways that initiate, amplify, and resolve pain. In this Review, we synthesize recent advances across visceral and somatic pain, highlighting the impact of sex hormones, immune-neural cross-talk, the gut microbiome, and endogenous analgesic circuits. Rather than clinging to the historical standard that simply described the female bias in pain symptoms, these studies begin to explain why females experience heightened pain, paving the path for mechanism-based precision therapeutics.