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Cromolyn inhibits PGE2-mediated sensitisation of TRPV1 in a GPR35-dependent manner in sensory neurons

Higham, J. P.; Paine, L. W.; Cameron, A.; Winchester, W.; Smith, E. S. J.; Srinivasan, N.; Suzuki, R.; Hockley, J. R.; Bulmer, D. C.

2026-01-23 neuroscience
10.64898/2026.01.21.700368 bioRxiv
Show abstract

There is a pressing need for effective alternatives to opioid analgesics, the development of which requires the identification of novel anti-nociceptive drug targets. Here, we have further investigated the anti-nociceptive properties of a GPR35 agonist, cromolyn, in an in vitro model of inflammatory sensitisation. We used ratiometric Ca2+ imaging of cultured sensory neurons to examine the effect of cromolyn on prostaglandin E2 (PGE2)-mediated sensitisation of the pro-nociceptive ion channel, transient receptor potential cation channel, subfamily V, member 1 (TRPV1). The sensitisation of TRPV1 by PGE2 was inhibited by cromolyn in a GPR35-dependent manner. These observations provide further evidence in support of an anti-nociceptive role for GPR35, highlighting the potential use of GPR35 agonists as analgesics.

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