title: 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. Histamine, chloroquine, and capsaicin intradermally 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. Among neurons retrogradely labeled from the thalamus, 43%, 8%, and 22% were Fos-positive following id histamine, chloroquine, or capsaicin. Among 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. Among the neurons retrogradely labeled from LPb, 36%, 29%, and 33% were Fos positive following id injection of histamine, chloroquine, and capsaicin, respectively. Among 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.
authors.affiliation: Temple Itch Center, Department of Dermatology, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, 95616.
authors.forename: Eric
authors.initials: E
authors.lastname: Curtis
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, 95616.
authors.forename: Tony
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, 95616.
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, 95616.
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D001931:Brain Mapping; D002211:Capsaicin / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D065823:Parabrachial Nucleus / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D013266:Stilbamidines; D013788:Thalamus / Q000166:cytology*; D014279:Trigeminal Nucleus, Spinal / Q000502:physiology*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000982:Antipruritics; D017442:Histamine Agonists; D016761:Oncogene Proteins v-fos; D013266:Stilbamidines; D006632:Histamine; D002738:Chloroquine; D002211:Capsaicin
keywords: Fos; double label; interneurons; itch (pruritus); pain; superficial dorsal horn; trigeminal projection neurons