A novel spinal neuron connection for heat sensation

Somatotopic localization of c-Fos expression in the spinal cord in response to noxious heat sensation

“…In this study the authors used c-Fos::shEGFP mice that express a short half-life enhanced green fluorescent protein (shEGFP) under the control of endogenous c-Fos promoter to characterize the neurons which are involved in heat sensations. When mice were exposed to noxious heat stimuli by using 52°C hot plate, compared with mice exposed to 25°C plate, shEGFP expression was increased in neurons of spinal cord dorsal horns (Figures 1B,C, in Wang et al, 2022 ). The authors confirmed that those shEGFP +ve neurons also overlapped with the same neurons labeled with c-Fos antibody, demonstrating its validity as a good indicator of activated neurons in the dorsal horn of the spinal cord.…”

“…The shEGFP+ neurons were individually isolated and subjected to single-cell RT-PCR to determine the co-expression of a number of other neuronal markers. Results showed that 78% of shEGFP +ve cells were positive for excitatory neurons which contain Vglut2 (vesicular glutamate transporter) whereas 22% were positive for inhibitory neurons which contain GAD65/67 (glutamate decarboxylase 65/67) (Figures 1G,H, in Wang et al, 2022 ). Moreover, following noxious heat, 33% of c-Fos +ve neurons also expressed ErbB4 (Figures 1M,N, in Wang et al, 2022 ).…”

“…Results showed that 78% of shEGFP +ve cells were positive for excitatory neurons which contain Vglut2 (vesicular glutamate transporter) whereas 22% were positive for inhibitory neurons which contain GAD65/67 (glutamate decarboxylase 65/67) (Figures 1G,H, in Wang et al, 2022 ). Moreover, following noxious heat, 33% of c-Fos +ve neurons also expressed ErbB4 (Figures 1M,N, in Wang et al, 2022 ). In addition to several other techniques used in this study, the authors concluded that the data provide evidence for the involvement of spinal ErbB4 +ve neurons in heat hypersensitivity in inflammatory and neuropathic pain.…”

“…The medial part of the dorsal horn receives the termination of the primary afferents from the limbs through the ventral ramus, while the lateral part receives the termination of the primary afferents from the skin of the back through the dorsal ramus ( Figure 1A ). Therefore, exposing the hind paw of mice to noxious heat stimuli, as carried out by Wang et al ( 2022 ), should cause neuronal activation which in turn would lead to c-Fos induction in the medial part of the dorsal horn. This has been extensively demonstrated in rodents in different laboratories in which c-Fos was induced by either radiant heat pulses (52°C; Figures 2, 3 in Hunt et al, 1987 ) or the injection of formalin into plantar skin (Figures 1, 3 in Todd et al, 1994 ) or the immersion hind paw in 55°C water bath (Figure 4E in Cavanaugh et al, 2009 ).…”

“…We have read with great interest the manuscript entitled “A novel spinal neuron connection for heat sensation” by Wang et al ( 2022 ) published in Neuron 110, 1–19, 2022. In this study the authors used c-Fos::shEGFP mice that express a short half-life enhanced green fluorescent protein (shEGFP) under the control of endogenous c-Fos promoter to characterize the neurons which are involved in heat sensations.…”