Anatomical evidence of pruriceptive trigeminothalamic and trigeminoparabrachial projection neurons in mice

Abstract

Itch is relayed to higher centers by projection neurons in the spinal and medullary dorsal horn. We employed a double-label method to map the ascending projections of pruriceptive and nociceptive trigeminal and spinal neurons. The retrograde tracer fluorogold (FG) was stereotaxically injected into the right thalamus or lateral parabrachial area (LPb) in mice. Seven days later, mice received intradermal (id) microinjection of histamine, chloroquine, capsaicin, or vehicle into the left cheek. Id histamine, chloroquine and capsaicin elicited similar distributions of Fos-positive neurons in the medial aspect of the superficial medullary and spinal dorsal horn from the trigeminal subnucleus caudalis to C2. Of neurons retrogradely labeled from the thalamus, 43, 8 and 22% were Fos-positive following id histamine, chloroquine or capsaicin. Of the Fos-positive neurons following pruritic or capsaicin stimuli, ∼1–2% were retrogradely labeled with FG. Trigeminoparabrachial projection neurons exhibited a higher incidence of double-labeling in the superficial dorsal horn. Of the neurons retrogradely labeled from LPb, 36, 29 and 33% were Fos-positive following id injection of histamine, chloroquine or capsaicin, respectively. Of Fos-positive neurons elicited by id histamine, chloroquine and capsaicin, respectively, 3.7, 4.3 and 4.1% were retrogradely labeled from LPb. The present results indicate that, overall, relatively small subpopulations of pruriceptive and/or nociceptive neurons innervating the cheek project to thalamus or LPb. These results imply that the vast majority of pruritogen- and algogen-responsive spinal neurons are likely to function as interneurons relaying information to projection neurons and/or participating in segmental nocifensive circuits.

Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray

“…However, whether itch and pain information are integrated into the same or different neuronal populations is currently a matter of controversy. In agreement with the concept of shared processing nodes, recent studies support the notion of a robust itch modulatory system within regions of the nervous system that are related to nociception [6][7][8][9][10][11][12][13] . For example, scratching the skin reduces the firing rate of primate spinothalamic tract (STT) neurons responding to pruritogens, but does not alter neuronal responses to painful stimuli 14 .…”

Kölliker–Fuse GABAergic and glutamatergic neurons project to distinct targets

“…To date, the PB complex has been related to control of breathing, blood pressure, blood volume and osmolarity, ingestive behavior, behavioral state, and sensory processing of taste, pain, itch, and skin temperature (Spector, Norgren, & Grill, 1992; Buritova, Besson, & Bernard, 1998; Wu, Clark, & Palmiter, 2012; Davern, 2014; Akiyama, Curtis, Nguyen, Carstens, & Carstens, 2016; Morrison, 2016; Saper & Loewy, 2016). The KF in particular is implicated largely in respiratory control (Dutschmann & Dick, 2012).…”

Central Mechanisms of Itch

“…1). In rodents, many spinothalamic and spinoparabrachial neurons respond to multiple pruritogens [29–31]. Interestingly, most or all pruritogen-responsive neurons are also excited by the algogens capsaicin and mustard oil, as well as other pain-producing stimuli.…”