Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat inflammatory pain, but they can have severe side effects, including potentially life-threatening gastrointestinal, renal and cardiac toxicity. Their analgesic effect is driven by inhibition of prostaglandin (PG) biosynthesis and subsequent inflammation, but this inhibitory effect on inflammation could delay pain resolution. An optimal approach to managing PG-mediated pain would selectively relieve pain while preserving the PGs’ essential inflammatory and protective functions.

The U.S. FDA issued new guidance for the development of non-opioid analgesics for chronic pain indications, with specific details on trial design, patient populations and meaningful outcomes, including reducing the nation’s reliance on opioids.

Bright Minds Biosciences Inc. has released preclinical results for BMB‑201, a selective 5-HT2A/2C receptor agonist, in a validated isosorbide dinitrate (ISDN) rat model of vascular headache. BMB-201 is designed to harness the analgesic potential of serotonin modulation without the hallucinogenic effects commonly associated with 5-HT2A activation.

G protein-biased agonists enhance opioid-induced analgesia by selectively avoiding β-arrestin-2 (βarr2) signaling, which has been associated with reduced efficacy and adverse effects. Similarly, directing neurotensin receptor 1 (NTSR1) signaling toward β-arrestin pathways may promote analgesia via alternative mechanisms while minimizing side effects linked to G protein activation.