A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region

SRP-001 is presented as a safer, non-hepatotoxic analgesic alternative to acetaminophen (ApAP) for inflammatory pain. The study tests SRP-001 versus ApAP using a CFA-induced inflammatory pain model and focuses on the periaqueductal gray (PAG) brain region. It reports that SRP-001 generates AM404 in PAG, activates TRPV1 for central analgesia, and avoids the hepatotoxic pathway associated with ApAP overuse. Cell-specific genomic and epigenomic profiling using coupled RNA and ATAC sequencing highlights restoration of key transcriptional programs and neural support signals. The results include changes in transcription factor families (SOX, SP/KLF, AP-1) and altered neuron-neuron interaction signaling linked to neurexin-neuregulin pathways, with SRP-001 achieving similar antinociceptive effects to ApAP while aiming to reduce liver risk.