Liu X, Wang D, Wen Y, Zeng L, Li Y, Tao T, Zhao Z, Tao A. Spinal GRPR and NPRA Contribute to Chronic Itch in a Murine Model of Allergic Contact Dermatitis. (2020) J Invest Dermatol 140(9):1856-1866.e7. doi: 10.1016/j.jid.2020.01.016
Meng J, Chen W, & Wang J. Intervening B-Type Natriuretic Peptide Signaling for Controlling Chronic Itch. (2020) Brit J Pharmacol, 177(5):1025-1040. doi: 10.1111/bph.14952
Objective: Review of recent findings used to examine the role of B-type natriuretic peptide (BNP) in itch transduction and the modulation of other pururitic proteims.
Summary: Mice treated with Nppb-saporin, a toxin ablated 70% BNP receptor positive neurons in the spinal cord (Mishra & Hoon, 2013; Pitake, Ralph, DeBrecht & Mishra, 2018).
Fatima M, Ren X, Pan H, Slade HFE, Asmar AJ, Xiong CM, Shi A, Xiong AE, Wang L, & Duan B. Spinal somatostatin-positive interneurons transmit chemical itch. (2019) PAIN, 160 (5):1166-1174. doi: 10.1097/j.pain.0000000000001499
Objective: To further study the cellular identity of spinal interneurons that contribute to itch processing.
Summary: Findings reveal a novel spinal mechanism for sensory encoding of itch perception.
Dose: Npra receptor–expressing spinal cord interneurons were ablated through intrathecal injection of Nppb-SAP (5 μg/10 μL) or control Blank-SAP in lumbar segment 3 to 4. Behavioral analyses were performed 1 week after the toxin injection.
Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, Hor CC, Zaher N, Cin M, Slade H, Huang T, Xu XZS, Duan B. Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch. (2019) Neuron 103(6):1135-1149.e6. doi: 10.1016/j.neuron.2019.06.016
IT-40: Bombesin-SAP; IT-69: Nppb-SAP; IT-21: Blank-SAP
Objective: To identify a spinal circuit for mechanical and persistent spontaneous itch.
Summary: Findings indicate excitatory interneurons expressing Urocortin 3::Cre (Ucn3+) in the dorsal spinal cord as a valid cellular target for future therapeutic interventions against chronic itch, without affecting normal touch.
Dose: To ablate spinal GRPR+ neurons, mice were given a single intrathecal injection of either Bombesin-SAP or Blank-SAP (400 ng in 10 mL sterile saline). To ablate spinal Npra+ neurons, mice were given a single intrathecal injection of either Nppb-SAP or Blank-SAP (5 mg in 10 mL sterile saline).
Sakata D, Uruno T, Matsubara K, Andoh T, Yamamura K, Magoshi Y, Kunimura K, Kamikaseda Y, Furue M, & Fukui Y. Selective role of neurokinin B in IL-31–induced itch response in mice. (2019) J Allergy Clin Immunol, 144 (4):1130-1133. doi: 10.1016/j.jaci.2019.06.031
Objective: To examine the physiological significance of neurokinin B in IL-31–induced itch sensation.
Summary: IL-31–induced scratching was unaffected by intrathecal injection of Nppb-SAP. In contrast, treatment with Bombesin-SAP reduced IL-31–induced scratching. Neurokinin B acts upstream of GRP to transmit IL-31–induced itch sensation.
Dose: Intrathecal injection.
Pitake S, Ralph PC, DeBrecht J, & Mishra SK. Atopic Dermatitis Linked Cytokine Interleukin-31 Induced Itch Mediated via a Neuropeptide Natriuretic Polypeptide B. (2018). Acta Derm Venereol, 98 (8):795-796. 2018/05/26.
Objective: To determine if NPPB is involved as a neuropeptide in IL-31-mediated itch in atopic dermatitis (AD) via natriuretic polypeptide receptor A (NPRA) in the spinal cord.
Summary: This study reveals an important role of neuropeptide NPPB in AD that could provide a therapeutic target for alleviating chronic itch associated with AD.
Dose: To further demonstrate the IL-31-mediated itch response by NPRA receptors expressed in the spinal cord, Nppb-SAP (5 μg) was used to eliminate neurons expressing NPRA receptors in the spinal cord.
Huang J, Polgár E, Solinski HJ, Mishra SK, Tseng P-Y, Iwagaki N, Boyle KA, Dickie AC, Kriegbaum MC, Wildner H, Zeilhofer HU, Watanabe M, Riddell JS, Todd AJ, & Hoon MA. Circuit Dissection of the Role of Somatostatin in Itch and Pain. (2018). Nature Neuroscience.
Objective: To determine the role of somatostatin in itch and pain.
Summary: Results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.
Dose: Ablation of Npr1- and GRPR-expressing spinal cord interneurons was accomplished by intrathecal (segment L3/4) injection of Nppb-SAP (4 μg/10 μL) and Bombesin-SAP (2.5 μg) respectively.
Mishra SK, Hoon MA. (2013) The cells and circuitry for itch responses in mice. Science 340(6135):968-971. (Targeting Trends 13q3)