Document Type

Article

Publication Date

1-1-2025

Publication Title

Neurobiology of pain (Cambridge, Mass.)

Abstract

Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP's limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, from the periaqueductal gray (PAG) midbrain region, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund's adjuvant (CFA)-induced inflammatory pain against no treatment and vehicle controls. Our analysis revealed differential activity in three transcription factor families (SOX, SP/KLF, and AP-1) with cell-specific patterns and altered neuron-neuron interactions through neurexin-neuregulin signaling. SRP-001 and ApAP demonstrated similar genetic and epigenetic outcomes, indicating that SRP-001 is a favorable alternative due to its non-hepatotoxic properties while maintaining the same antinociceptive effects as ApAP.

First Page

100192

PubMed ID

40746432

Volume

18

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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