N addition to TRPV1 and V2 as heat Retinol web sensors, TRPA1 (Kwan et al. 2006; but see Bautista et al. 2006) and TRPM8 (Bautista et al. 2007; Colburn et al. 2007; Dhaka et al. 2007) have already been reported as cold sensors. TRPV1, TRPM8 and TRPA1 are expressed preferentially in smaller neurons of mature rat DRG (Kobayashi et al. 2005). Of lumbar DRG neurons, 47 express TRPV1 mRNA or IR in adult rat (Michael and 1533426-72-0 custom synthesis Priestley 1999; Orozco et al. 2001; Kobayashi et al. 2005) and 22 eight show TRPV1 IR in adult mice (Orozco et al. 2001; Zwick et al. 2002). In adultCell Tissue Res (2008) 333:353rat DRG, 23 and 40 of the neurons express TRPM8 and TRPA1 mRNA, respectively (Kobayashi et al. 2005). The TRPV1-expressing population contains the TRPA1-positive cells (Kobayashi et al. 2005) but overlap with TRPM8 is restricted. Of TRPM8 mRNA-positive cells, 30 are TRPV1-immunoreactive in rat (Okazawa et al. 2004) and no overlap is discovered in mice (Peier et al. 2002; Dhaka et al. 2008). TRPM8-positive cells in mice have already been shown by EGFP expression in the TRPM8 locus to mark a exclusive population of DRG neurons, the majority of which does not coexpress nociceptive markers (Dhaka et al. 2008). In adult rat, 60 on the TRPV1-immunoreactive cells in L5 DRG show ret IR (Guo et al. 2001). In adult rat and mouse, 97 and 99 of GFRalpha3-immunoreactive L5 DRG neurons are TRPV1-immunoreactive, respectively, but 50 with the TRPV1-immunoreactive neurons are usually not GFRalpha3-positive (Orozco et al. 2001). TRPV1 expression and IB4 binding overlap to different degrees in rodents. In adult rat, 50 five of IB4-binding neurons express TRPV1 (Michael and Priestley 1999; Guo et al. 2001; Price tag and Flores 2007) and 70 0 of TRPV1-immunoreactive cells bind IB4 (Guo et al. 2001; Value and Flores 2007). In mice, only 2 of IB4-binding neurons in L4/5 DRG express TRPV1 IR (Zwick et al. 2002; Woodbury et al. 2004; Breeze et al. 2005). No IB4-binding is observed in TRPM8-expressing DRG neurons in mouse (Peier et al. 2002; Dhaka et al. 2008). TRPV1, TRPM8 and TRPA1 are coexpressed with trkA, whereas overlap together with the trkB- and trkC-positive population is minor (4 ) in adult rat (Kobayashi et al. 2005). TRPV1 and TRPA1 expression overlaps partially with trkA in adult rat DRG. Approximately 45 with the TRPV1- and TRPA1positive cells express trkA, whereas 51 5 (Kobayashi et al. 2005; Michael and Priestley 1999) and 36 (Kobayashi et al. 2005) with the trkA-positive cells express TRPV1 and TRPA1, respectively. Double ISH has shown the expression of trkA in virtually all TRPM8-positive cells (98 ), with practically half (43 ) of trkA-positive neurons expressing TRPM8. During mouse improvement, TRPV1-immunoreactive cells are 1st detected at E13.five in DRG neurons (Tamura et al. 2005). Capsaicin responses are rarely observed in acutely dissociated DRG cells from E11.five DRG having a sturdy improve in the proportion of responsive cells between E12.5 (five ) and E14.five (64 ) along with a postnatal decline to 40 (Hjerling-Leffler et al. 2007). TRPM8 is first detected at E16.5 by ISH (Chen et al. 2006). IR is just not detected at E15.five but in few cells at E17.5 (Tamura et al. 2005). This coincides nicely together with the onset of menthol responsiveness in cultures taken from E16.5 mouse embryos (Hjerling-Leffler et al. 2007). Throughout rat postnatal development, the proportion of TRPV1-immunoreactive cells coexpressing ret increases from 30 at P2 to 50 at P10 and 60 at P40 (Guo et al. 2001).The proportion of TRPV1-immunoreactive cells that.