I am a
Home I AM A Search Login

Papers of the Week

Papers: 25 Jan 2020 - 31 Jan 2020

Animal Studies, Pharmacology/Drug Development

2020 05 01

J Clin Invest



GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents.


Yosten G L, Harada CM, Haddock CJ, Giancotti L A, Kolar GR, Patel R, Guo C, Chen Z, Zhang J, Doyle TM, Dickenson AH, Samson WK, Salvemini D
J Clin Invest. 2020 05 01; 130(5):2587-2592.
PMID: 31999650.


Treating neuropathic pain is challenging and novel non-opioid based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence and in situ hybridization, we found the expression of the orphan GPCR (oGPCR) Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord (DH-SC) following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal (i.th.) CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights to its signaling pathways. CARTp is involved in many diseases including depression, reward and addiction, de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.