Table 1.
| Gene | Location | Evidence For | References | Evidence Against | References |
|---|---|---|---|---|---|
| TRPV1 | Peripheral | Peripheral TRPV1 agonists induce hypothermia and activate preoptic warm-sensitive neurons | (Hori, 1984; Nakayama et al., 1978; Tan et al., 2016) | Some effects of peripheral TRPV1 agonists may be centrally mediated | (Hori, 1984; Romanovsky et al., 2009) |
| Peripheral TRPV1 antagonists induce hyperthermia | (Gavva, 2008; Gavva et al., 2007) | TRPV1 antagonist induced hyperthermia is independent of temperature | (Romanovsky et al., 2009; Steiner et al., 2007) | ||
| TRPV1 can be activated by warm temperatures following sensitization by endogeneous co-agonists | (Cao et al., 2013; Tominaga et al., 1998; Vellani et al., 2001) | Temperature threshold of purified TRPV1 (~42 C) is above the range of innocuous warmth | (Cao et al., 2013; Caterina et al., 1997) | ||
| TRPV1 antagonists block the activation of sensory neurons by innocuous warmth in vivo | (Yarmolinsky et al., 2016) | TRPV1 knockout or ablation of TRPV1 + neurons has little or no effect on body temperature or thermoregulation | (Caterina et al., 2000; Garami et al., 2011; Iida et al., 2005; Pogorzala et al., 2013) | ||
| TRPV1 | Central | Central capsaicin can induce hypothermia | (Hori, 1984) | TRPV1 expression is extremely sparse in the brain and absent from preoptic area | (Cavanaugh et al., 2011) |
| The requirement for TRPV1 in the response to brain warming or central capsaicin has not been reported | |||||
| TRPM2 | Central or peripheral | TRPM2 KO diminishes the activation of neurons by warming in hypothalamic slices or DRG cultures | (Song et al., 2016; Tan and McNaughton, 2016) | TRPM2 is broadly expressed in the brain and periphery and does not specifically label thermoregulatory cells | (Song et al., 2016; Tan and McNaughton, 2016) |
| TRPM2 KO mice have a mildly elevated fever in response to PGE2 and show reduced preference for warm temperatures | (Song et al., 2016; Tan and McNaughton, 2016) | TRPM2 KO mice have normal core body temperature, and the response to brain warming and other thermoregulatory challenges has not been reported | |||
| TRPV3 | Peripheral | Heterologous TRPV3 is activated by innocuous warmth (threshold ~32 C), | (Peier et al., 2002; Smith et al., 2002; Xu et al., 2002) | The thermosensory deficits in TRPV3 KO mice are strain and sex-dependent | (Huang et al., 2011; Miyamoto et al., 2011) |
| TRPV3 KO mice have impaired thermosensation | (Moqrich et al., 2005) | TRPV3/TRPV4 double KO mice have normal thermosensation | (Huang et al., 2011) | ||
| TRPV4 | Peripheral | Heterologous TRPV4 is activated by innocuous warmth (threshold ~34 C) | (Guler et al., 2002) | TRPV4 KO mice and TRPV3/TRPV4 double KO mice have normal thermoregulation | (Huang et al., 2011; Liedtke and Friedman, 2003) |
| TRPV4 KO mice have impaired thermosensation and a peripheral TRPV4 antagonist increases body temperature | (Lee et al., 2005; Vizin et al., 2015) |
References
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