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.

doi:10.64898/2026.01.21.700368

bioRxiv · 10.64898/2026.01.21.700368

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.

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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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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. Cromolyn inhibits PGE2-mediated sensitisation of TRPV1 in a GPR35-dependent manner in sensory neurons. https://doi.org/10.64898/2026.01.21.700368

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