Mu opioid receptors (MOR) agonists exert strong anti-nociceptive activity but their ability to cause tolerance and physical dependence are serious issues of concern and limit their use. The activation of another branch of opioid receptors discovered lately, the opioid-related nociceptin receptor 1 (OPRL1) has recently shown the ability to enhance MOR agonist-induced analgesia while limiting tolerance and side effects.

Over the last six years, more than 20,000 patients have been implanted with the Sprint PNS system to manage acute or chronic pain, SPR Therapeutics Inc. reported. The 20,000th patient was treated for low back and leg pain with the Sprint Extensa XT system, which like the company’s other systems is implanted for 60 days in a minimally invasive surgery. The system uses percutaneous peripheral nerve stimulation (PNS) to recondition the central nervous system to provide long-term, significant relief from pain.

With overuse of opioids – the standard of care for many chronic pain cases – becoming something of an epidemic in the U.S., the availability of an alternative, non-opioid analgesic is a big draw. Established in 2021, Adolore Biotherapeutics Inc. is one company that could provide the answer, with its locally and long-acting gene therapies potentially providing a breakthrough that “knocks everybody’s socks off.”

With overuse of opioids – the standard of care for many chronic pain cases – becoming something of an epidemic in the U.S., the availability of an alternative, non-opioid analgesic is a big draw. Established in 2021, Adolore Biotherapeutics Inc. is one company that could provide the answer, with its locally and long-acting gene therapies potentially providing a breakthrough that “knocks everybody’s socks off.”

Researchers have developed a new highly effective therapeutic for pain relief by altering the chemical properties of an antinausea drug, netupitant. The modified drug is able to enter the intracellular membrane-bound endosome and target the GPCRs therein, rather than at the cell surface, that leads to optimal pain relief. The study, published in the Proceedings of the National Academy of Sciences (PNAS) on May 22, 2023, was led by Nigel Bunnett, Professor and Chair of Molecular Pathobiology at NYU College of Dentistry, and illustrates how GPCR-mediated pain signaling occurs inside the endosomes rather than at the surface, highlighting the need for drugs that can reach receptors within the cells itself.

Patients with irritable bowel syndrome (IBS) have chronic abdominal pain as a result of visceral hypersensitivity. Voltage-gated sodium channels control cellular excitability and are involved in the pathophysiology of several functional gastrointestinal disorders. Researchers from Nocion Therapeutics Inc. and the University of Oklahoma recently reported on the preclinical testing of NTX-1175, a sodium-channel blocker, in rat models of acute colonic hypersensitivity to distension.

Researchers have used cell culture experiments to understand how gene expression was affected in a patient with a rare pain insensitivity syndrome, and have identified a network of hundreds of genes whose expression was changed compared to sex-matched controls. Published online in the journal Brain on May 23, 2023, the research is one step toward translating a rare mutation into medications that could provide benefits for common ailments.