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The pharmacotherapeutic potential of neuropeptide Y for chronic pain
Nie AA, Taylor BK (2025) The pharmacotherapeutic potential of neuropeptide Y for chronic pain. J Intern Med doi: 10.1111/joim.20118 PMID: 40754889
Objective: To evaluate how neuropeptide Y (NPY) and its receptor subtypes (Y1 and Y2) regulate acute and chronic pain, and to explore the therapeutic potential of targeting these pathways for the treatment of neuropathic and inflammatory pain.
Summary: The review highlights that spinal Y1-interneurons contribute to both sensory and affective components of chronic pain and that Y1 receptor activation can inhibit pronociceptive signaling. Prior studies using NPY-SAP demonstrated that ablation of Y1-expressing neurons reduces hypersensitivity in models of nerve injury and inflammation, supporting Y1 modulation as a therapeutic avenue.
Usage: NPY-SAP (IT-28) was referenced in the context of earlier studies employing intrathecal administration to ablate spinal Y1-interneurons.
Related Products: NPY-SAP (Cat. #IT-28)
See Also:
- Nelson TS et al. Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248, 2019.
- Lemons LL et al. Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation. Neuroscience 216:158-166, 2012.
Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding
Choi PP, Wang Q, Brenner LA, Li AJ, Ritter RC, Appleyard SM (2024) Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding. Endocrinology 165(5):bqae021. doi: 10.1210/endocr/bqae021 PMID: 38368624
Objective: To explore the role of NPY receptor-expressing neurons in regulating feeding behavior in rats.
Summary: In response to glucose deficits, rats exhibit counter-regulatory mechanisms to stimulate feeding. To clarify the role of NPY-sensitive neurons, these neurons were selectively ablated using NPY-SAP. The results showed that while Saporin-lesioned rats exhibited reduced 2DG-induced feeding, there was no impact on 2DG-induced locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release.
Usage: NPY-SAP [IT-28] or Blank-SAP [IT-21] (50 ng per 100nL/site) was used to specifically lesion NPY receptor-expressing neurons in the perifornical lateral hypothalamus of male rats.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
The VLM a1/c1 ca/npy neuronal projections to the perifornical area of the lateral hypothalamus and its functional role in glucoprivic feeding
Choi P (2023) The VLM a1/c1 ca/npy neuronal projections to the perifornical area of the lateral hypothalamus and its functional role in glucoprivic feeding. Washington State Univ Thesis.
Objective: This dissertation aimed to determine the role of neuropeptide Y (NPY) receptor signaling from the ventrolateral medulla (VLM) catecholamine (CA) neurons in the lateral hypothalamus (LHA) for glucoprivic feeding.
Summary: The results showed that NPY receptor-expressing neurons in the perifornical area of the LHA are required for glucoprivic feeding evoked by 2-deoxyglucose. Furthermore, antagonism of NPY Y1 or Y2 receptors in the LHA attenuated feeding evoked by chemogenetic activation of VLM CA neurons, indicating NPY release from VLM neurons activates LHA NPY receptors to elicit glucoprivic feeding.
Usage: NPY-SAP (50 ng per 100 nL/site) or control Blank-SAP (50 ng per 100 nL/site) dissolved in 0.01 M phosphate buffer was infused slowly over a 5 minute period directly into the perifornical lateral hypothalamic (stereotaxic coordinate: 2.8 mm caudal from bregma, +/- 1.2 mm lateral to the midline, and -7.4 mm from the dura mater) through a pulled glass capillary pipette (30 µm tip diameter) connected to a Picospritzer. The rats were allowed at least 7 days for a full recovery from surgery and NPY-SAP-induced neuronal ablation.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Targeting spinal neuropeptide Y1 receptor-expressing interneurons to alleviate chronic pain and itch
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: 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. (Wiley et al.) 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). (Nelson et al.) 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.
Related Products: NPY-SAP (Cat. #IT-28)
See Also:
- Wiley RG et al. Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147, 2009.
- Nelson TS et al. Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248, 2019.
Intra-articular injection of 2-pyridylethylamine produces spinal NPY-mediated antinociception in the formalin-induced rat knee-joint pain model
Souza-Silva E, Stein T, Mascarin LZ, Dornelles FN, Bicca MA, Tonussi CR (2020) Intra-articular injection of 2-pyridylethylamine produces spinal NPY-mediated antinociception in the formalin-induced rat knee-joint pain model. Brain Res 1735:146757. doi: 10.1016/j.brainres.2020.146757 PMID: 32135147
Objective: To investigate the participation of spinal NPY in the antinociceptive effect produced by 2-pyridylethylamine (2-PEA).
Summary: These data support the idea that antinociception induced by H1R agonists in the knee-joint of rats may be mediated by the spinal release of NPY, and this peptide seems to be acting via Y1R.
Usage: IT pretreatment with NPY-SAP (750 ng) reduced immunoblotting for Y1R in spinal cord homogenates.
Related Products: NPY-SAP (Cat. #IT-28)
Hindbrain glucoregulatory mechanisms: Critical role of catecholamine neurons in the ventrolateral medulla.
Ritter S, Li A-J, Wang Q (2019) Hindbrain glucoregulatory mechanisms: Critical role of catecholamine neurons in the ventrolateral medulla. Physiol Behav 208:112568. doi: 10.1016/j.physbeh.2019.112568
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.
Related Products: Anti-DBH-SAP (Cat. #IT-03), NPY-SAP (Cat. #IT-28)
Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.
Marvizon JC, Chen W, Fu W, Taylor BK (2019) Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury. 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. Ablation of Y1-expressing dorsal horn neurons with NPY-saporin produced antinociception (Lemons and Wiley) and reduced mechanical and cold hypersensitivity in the spared nerve injury model (Nelson et al.), suggesting that they are pro-nociceptive neurons.
Related Products: NPY-SAP (Cat. #IT-28)
See Also:
Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn.
Nelson TS, Fu W, Donahue RR, Corder GF, Hökfelt T, Wiley RG, Taylor BK (2019) Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248. doi: 10.1038/s41598-019-43493-z PMID: 31076578
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.
Usage: 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).
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Neuropeptide Y and its involvement in chronic pain
Diaz-delCastillo M, Woldbye DPD, Heegaard AM (2018) Neuropeptide Y and its involvement in chronic pain. Neuroscience 387:162-169. doi: 10.1016/j.neuroscience.2017.08.050
Related Products: NPY-SAP (Cat. #IT-28)
Toxins as tools: Fingerprinting neuronal pharmacology.
Israel MR, Morgan M, Tay B, Deuis JR (2018) Toxins as tools: Fingerprinting neuronal pharmacology. Neurosci Lett 679:4-14. doi: 10.1016/j.neulet.2018.02.001
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.
Related Products: IB4-SAP (Cat. #IT-10), NPY-SAP (Cat. #IT-28)