SLC45A4 is a pain gene encoding a neuronal polyamine transporter
Overview
Paper Summary
This study used human genetic data and mouse models to identify SLC45A4, a gene encoding a polyamine transporter, as being associated with chronic pain intensity, particularly for heat and tonic pain. Mice lacking this gene had reduced sensitivity to these types of pain, alongside changes in polyamine levels. The study also found changes in GABA levels in the spinal cord of knockout mice.
Explain Like I'm Five
Scientists found a gene, SLC45A4, that's involved in how we feel pain, especially heat and long-lasting pain. Mice lacking this gene were less sensitive to heat and certain types of pain.
Possible Conflicts of Interest
J.E.L. is an employee of AstraZeneca. D.L.B. received consulting fees from various pharmaceutical companies. The PAINSTORM consortium received funding from Eli Lilly and AstraZeneca. The DOLORisk consortium received funding from Eli Lilly. H.R.K. has financial ties to several pharmaceutical companies, including advisory board positions, consulting fees, research funding, and is listed as an inventor on a patent related to buprenorphine treatment response.
Identified Limitations
Rating Explanation
This study presents strong evidence for SLC45A4's role in pain perception, combining human genetic data with mechanistic studies in mice. The multi-faceted approach, including GWAS, cell assays, structural biology, and behavioral experiments strengthens the findings. However, the reliance on mouse models and the lack of a full mechanistic understanding limit the rating to a 4.
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