RYR1 and cancer: We also performed function analysis of the top 20 DEGs of ion channels in pain perception by literature retrieval and found that many have been suggested to be associated with pain perception, e.g., Ryr1(encoding ryanodine receptor, RyR1) (Ferrari et al., 2016), Cnga3 (encoding cyclic nucleotide-gated ion channel α3, CNGA3) (Heine et al., 2011), Kcnj2 (encoding inwardly rectifying potassium channel 2.1, Kir2.1) (Ma et al., 2010), Trpv4 (encoding transient receptor potential vanilloid 4, TRPV4) (Todaka et al., 2004), surprisingly, none of them to be associated with cancer pain (Figure 6H).