Projecting neurons in spinal dorsal horn send collateral projections to dorsal midline/intralaminar thalamic complex and parabrachial nucleus

Microglia are involved in regulating histamine‐dependent and non‐dependent itch transmissions with distinguished signal pathways

“…In the ROSA iDTR ;CX3CR1 CreER/+ mice with microglia ablation, HA and C48/80 induced c‐fos up‐regulation were significantly inhibited compared with the WT groups, respectively ( p < .0001 for both) (Figures 3b and 4b). However, CQ‐induced total c‐fos up‐regulation was not reduced by microglia ablation ( p = .073), but the c‐fos + cell distribution were changed that the c‐fos + cells clustered in the lateral spinal nucleus (LSN) were significantly reduced ( p < .0001), where most of the ascending projection neurons were located (Li et al, 2021; Figure 5b). For the Npr1+ neurons, the percentage of c‐fos + cells were increased from 8.60 ± 0.66% to 23.50 ± 2.05% ( p < .0001) in the HA‐treated WT mice (Figure 3c), to 19.85 ± 1.97% ( p < .0001) in the C48/80‐treated WT mice (Figure 4c), to 26.7 ± 4.09% ( p < .0001) in the CQ‐treated WT mice (Figure 5c).…”

“…However, CQ-induced total c-fos up-regulation was not reduced by microglia ablation ( p = .073), but the c-fos + cell distribution were changed that the c-fos + cells clustered in the lateral spinal nucleus (LSN) were significantly reduced ( p < .0001), where most of the ascending projection neurons were located (Li et al, 2021; Figure 5b).…”

Structural and functional organization of the midline and intralaminar nuclei of the thalamus

“…The main sources of afferents to the rostral ILt arise from structures/regions of the brainstem and cortex. The following brainstem nuclei project to the rostral ILt: dorsal and median raphe nuclei (Vertes, 1991 ; Hermann et al, 1996 ; Morin and Meyer-Bernstein, 1999 ; Vertes et al, 1999 , 2010 ; Krout et al, 2002 ; Muzerelle et al, 2016 ; Urban et al, 2016 ), locus coeruleus (Jones and Yang, 1985 ; Krout et al, 2002 ), pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei (Hallanger et al, 1987 ; Hallanger and Wainer, 1988 ; Bolton et al, 1993 ), the ventral tegmental area (Beckstead et al, 1979 ; Krout et al, 2002 ), parabrachial complex (Bester et al, 1999 ; Krout and Loewy, 2000a ; Bourgeais et al, 2001 ; Iwai et al, 2015 ; Deng et al, 2020 ), periaqueductal gray (Cameron et al, 1995 ; Krout and Loewy, 2000b ; Kincheski et al, 2012 ; Sun et al, 2020 ), superior colliculus (Yamasaki et al, 1986 ; Krout et al, 2001 ), nucleus incertus (Goto et al, 2001 ; Olucha-Bordonau et al, 2003 ), the dorsal horn of the spinal cord (Li et al, 2021a ) and dense projections from the mesencephalic, pontine, and medullary reticular formation (Glenn and Steriade, 1982 ; Vertes et al, 1986 ; Vertes and Martin, 1988 ; Villanueva et al, 1998 ; Krout et al, 2002 ). The rostral ILt nuclei also receive significant, but more limited, input from diencephalic structures including the reticular nucleus of thalamus (Velayos et al, 1989 ; Kolmac and Mitrofanis, 1997 ), the zona incerta (Power et al, 1999 ; Power and Mitrofanis, 2001 ), the substantia nigra pars reticulata (McElvain et al, 2021 ), and the lateral and supramammillary nuclei of the hypothalamus (Vertes, 1992 ; Peyron et al, 1998 ).…”

Circuit Mechanisms of Itch in the Brain

“…It is thought that the spinoparabrachial tract and the PBN are involved in pain processing (Basbaum et al, 2009;Dunckley et al, 2005;Youssef et al, 2016). Several tracing and in vivo electrophysiological studies in rodents have shown that the PBN is also involved in itch processing (Akiyama et al, 2016;Jansen and Giesler, 2015;Li et al, 2021b). A study found that the PBN serves as a critical itch-processing nucleus .…”