Nelson TS, Taylor BK (2021) Targeting spinal neuropeptide Y1 receptor-expressing interneurons to alleviate chronic pain and itch. Prog Neurobiol 196:101894. doi: 10.1016/j.pneurobio.2020.101894
Summary: Tissue and nerve injury models of persistent pain. Intrathecal administration of NPY-SAP reduced several operant and cognitive measures of Complete Freund’s adjuvant (CFA)-induced allodynia, including responsiveness to cold temperatures, feeding interference, and an escape task, but did not interfere with systemic morphine-induced analgesia. [See Wiley RG, Lemons LL, Kline RHt. (2009) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147. doi: 10.1016/j.neuroscience.2008.12.017.] Similar to the spared nerve injury (SNI) model of neuropathic pain, NPY-SAP dose-dependently reduced the development of mechanical allodynia (hindpaw withdrawal response to von Frey filaments), mechanical hyperalgesia (response to blunt pin), and cold allodynia (hindpaw withdrawal response duration to acetone droplet evaporation). [See Nelson TS, Fu W, Donahue RR, Corder GF, Hökfelt T, Wiley RG, Taylor BK. Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. (2019) Sci Rep 9(1):7248. doi: 10.1038/s41598-019-43493-z.] Together, these directed lesion studies support the idea that the Y1-IN subpopulation of dorsal horn neurons is necessary for the maintenance of both mechanical and cold modalities of nociceptive transmission in chronic pain states.
Marvizon JC, Chen W, Fu W, Taylor BK. Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury. (2019) Neuropharmacology 158:107732. doi: 10.1016/j.neuropharm.2019.107732
Summary: NPY is released from dorsal horn interneurons or primary afferent terminals by electrical stimulation and by activation of TRPV1, PKA or NMDA receptors in. Release evoked by noxious and tactile stimuli increases after peripheral nerve injury.
Cites “Ablation of Y1-expressing dorsal horn neurons with NPY-saporin produced antinociception (Lemons and Wiley, 2012) and reduced mechanical and cold hypersensitivity in the spared nerve injury model (Nelson et al., 2019), suggesting that they are pro-nociceptive neurons.”
Nelson TS, Fu W, Donahue RR, Corder GF, Hökfelt T, Wiley RG, Taylor BK. Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. (2019) Sci Rep 9(1):7248. doi: 10.1038/s41598-019-43493-z
KIT-28: NPY-SAP, Blank-SAP
Objective: To test the relevance of the NPYY1 spinal population to the development and/or maintenance of acute and neuropathic pain.
Summary: This neuroanatomical and behavioral characterization of Y1R-expressing excitatory interneurons provides compelling evidence for the development of spinally-directed Y1R agonists to reduce chronic neuropathic pain.
Dose: Selectively ablated Y1R-expressing interneurons while sparing the central terminals of primary afferents. Rats received intrathecal injections of either NPY-SAP or Control Blank-SAP (1000 ng each).
Ritter S, Li A-J, & Wang Q. Hindbrain glucoregulatory mechanisms: Critical role of catecholamine neurons in the ventrolateral medulla. (2019) Physiol Behav 208:112568. doi: 10.1016/j.physbeh.2019.112568
IT-03: Anti-DBH-SAP and IT-28: NPY-SAP – REVIEW
Objective: To explore circuitry and potential glucose-sensing mechanisms that contribute to the functions of glucoregulatory catecholamine neurons in the ventrolateral medulla
Summary: Selective lesion of hindbrain catecholamine neurons abolishes glucoprivic elicitation of key counterregulatory responses. Selective chemogenetic activation of specific catecholamine populations elicits these responses.
Israel MR, Morgan M, Tay B, Deuis JR. Toxins as tools: Fingerprinting neuronal pharmacology. (2018) Neurosci Lett 679:4-14. doi: 10.1016/j.neulet.2018.02.001
IT-10: IB4-SAP, IT-28: NPY-SAP
Summary: This review article provides an overview of the experimental techniques used to assess the effects that toxins have on neuronal function, as well as discussion on toxins that have been used as tools, with a focus on toxins that target voltage-gated and ligand-gated ion channels.
Diaz-delCastillo M, Woldbye DPD, Heegaard AM. (2017) Neuropeptide Y and Its Involvement in Chronic Pain. Neuroscience PMID: 28890052
Young JK (2016) Hunger, Thirst, Sex, and Sleep: How the Brain Controls Our Passions. Rowman & Littlefield Publishers. ISBN 14221824X.
Bartness TJ, Keen-Rhinehart E, Dailey MJ, Teubner BJ. (2011) Neural and hormonal control of food hoarding. Am J Physiol Regul Integr Comp Physiol 301(3):R641-55. (Targeting Trends 11q4)
Wiater MF, Mukherjee S, Li AJ, Dinh TT, Rooney EM, Simasko SM, Ritter S. (2011) Circadian Integration of Sleep/Wake and Feeding Requires NPY-Receptor Expressing Neurons in the Mediobasal Hypothalamus. Am J Physiol Regul Integr Comp Physiol 301(5):R1569-83. (Targeting Trends 11q4)
See also: Society for Neuroscience 2011 Abstracts
Dailey MJ, Bartness TJ (2010) Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding. Brain Res 1323:94-108. (Targeting Trends 10q2)
Lyons AM, Thiele TE (2010) Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31(12):2193-2199. (Targeting Trends 11q1)
See also: Society for Neuroscience 2010 Abstracts
Wiley RG, Lemons LL, Kline RHt. (2009) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147. doi: 10.1016/j.neuroscience.2008.12.017. (Targeting Trends 09q3)
Li AJ, Dinh TT, Ritter S (2008) Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes. Peptides 29(10):1732-1739. (Targeting Trends 08q4)
See also: Society for Neuroscience 2008 Abstracts
Bugarith K DTT, Li AJ, Speth RC, Ritter S. (2006) Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake. Targeting Trends 7(4).
Bugarith K, Dinh TT, Li AJ, Speth RC, Ritter S (2005) Basomedial hypothalamic injections of neuropeptide Y-saporin (NPY-SAP) selectively disrupt hypothalamic controls of food intake. Endocrinology 146(3):1179-1191. (Targeting Trends 05q1)
Li AJ, Ritter S (2003) 2-Deoxy-D-Glucose (2DG) increases NPY mRNA expression in hindbrain neurons. Soc Neurosci Mtg, New Orleans, LA, Abstract #615.7.
Bugarith K, Ritter S, Dinh T (2001) Hyperphagia and obesity results from the injection of the immunotoxin neuropeptide Y (NPY)-saporin (NPY-SAP) into the paraventricular hypothalamus (PVH) of rats. Soc Neurosci Mtg, San Diego, CA, Abstract #948.2.