Biology subjects

Taylor, B. K.

Publications and source records attributed to Taylor, B. K..

5 recordsLinked to original sources

bioRxiv2025

De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain

Nerve damage induces a robust de novo expression of the pain-modulatory peptide neuropeptide Y (NPY) in large-diameter primary afferent neurons that innervate the dorsal horn of the spinal cord and the dorsal column nuclei. To determine whether this functions to modulate peripheral neuropathic pain, we selectively deleted the Npy gene in neurons of the dorsal root ganglion (DRG), without disruption of its expression in brain or dorsal horn neurons. We then subjected sensory neuron-specific NPY deletion mutant mice (Pirt-NPY) and their wild-type controls to either sham surgery, spared sural nerve injury (SNI) or spared tibial nerve injury (tSNI). Conditional Npy deletion did not change the severity or duration of static mechanical, dynamic mechanical, or cold allodynia in SNI or tSNI models, nor ongoing neuropathic pain as assessed with conditioned place preference to gabapentin. When injected after the resolution of tSNI-induced mechanical hypersensitivity (a latent pain sensitization model of chronic neuropathic pain), the NPY Y1 receptor-specific antagonist BIBO3304 equally reinstated mechanical hypersensitivity in Pirt-NPY mice and their wildtype controls. We conclude that nerve injury-induced upregulation of NPY in sensory neurons does not cause mechanical or cold hypersensitivity or ongoing pain, and that tonic inhibitory control of neuropathic pain by NPY in the spinal cord is mediated by release from dorsal horn interneurons rather than sensory neurons.

neuroscience↗

bioRxiv2024

A parabrachial hub for the prioritization of survival behavior

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses. Neural activity recordings and computational modeling demonstrate that activity in Y1R parabrachial neurons is elevated following injury, predicts functional coping behavior, and is inhibited by competing survival needs. Taken together, our findings suggest that parabrachial Y1 receptor-expressing neurons are a critical hub for endogenous analgesic pathways that suppress sustained pain states.

neuroscience↗

bioRxiv2022

Mechanical and Heat Hyperalgesia upon Withdrawal from Chronic Intermittent Ethanol Vapor depends on Sex, Exposure Duration and Blood Alcohol Concentration in Mice

Approximately half of patients with alcohol use disorder (AUD) report pain and this can be severe during withdrawal. However, many questions remain regarding the importance of sex, blood alcohol concentration (BAC), time course, and pain modality. To examine the impact of sex and BAC on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of Chronic Alcohol Withdrawal Induced Pain (CAWIP) in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor (CIEV) {+/-} pyrazole exposure for 4 weeks, 4 days/week to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hr after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of CIEV exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that CAWIP develops in a sex -, time -, and BAC - dependent manner in C57BL/6J mice.

animal behavior and cognition↗

bioRxiv2022

Endogenous μ-opioid - neuropeptide Y Y1 receptor synergy silences chronic postoperative pain

Tissue injury creates a delicate balance between latent pain sensitization (LS) and compensatory endogenous analgesia. Inhibitory G protein-coupled receptor (GPCR) interactions that oppose LS, including -opioid receptor (MOR) and neuropeptide Y Y1 receptor (Y1R) activity, persist in the spinal cord dorsal horn (DH) for months, even after the resolution of normal pain thresholds. Here, we demonstrate that following recovery from surgical incision, a potent endogenous analgesic synergy between MOR and Y1R activity persists within DH interneurons to reduce the intensity and duration of latent postoperative hyperalgesia and ongoing pain. Failure of such endogenous GPCR signaling to maintain LS in remission may underlie the transition from acute to chronic pain states.

neuroscience↗

bioRxiv2021

Fast A-type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the NPY Y1 receptor

Neuroanatomical and behavioral evidence indicates that neuropeptide Y Y1 receptor-expressing interneurons (Y1-INs) in the superficial dorsal horn (SDH) are predominantly excitatory and contribute to chronic pain. Using an adult ex vivo spinal cord slice preparation from Y1eGFP reporter mice, we characterized firing patterns in response to steady state depolarizing current injection of GFP-positive cells in lamina II, the great majority of which expressed Y1 mRNA (88%). Randomly sampled and Y1eGFP neurons exhibited five firing patterns: tonic (TF), initial burst (IBF), phasic (PF), delayed short-latency <180 ms (DSLF), and delayed long-latency >180 ms (DLLF). When studied at resting membrane potential, most RS neurons exhibited delayed firing, while most Y1eGFP neurons exhibited phasic firing and not delayed firing. A preconditioning membrane hyperpolarization produced only subtle changes in the firing patterns of randomly sampled neurons, but dramatically shifted Y1eGFP neurons to DSLF (46%) and DLLF (24%). In contrast to randomly sampled DSLF neurons which rarely exhibited spike frequency adaptation, Y1eGFP DSLF neurons were almost always rapidly adapting, a characteristic of nociceptive-responsive SDH neurons. Rebound spiking was more prevalent in Y1eGFP neurons (6% RS vs 32% Y1eGFP), indicating enrichment of T-type calcium currents. Y1eGFP DSLF neurons exhibited fast A-type potassium currents that are known to delay or limit action potential firing, and these were of smaller current density as compared to randomly sampled DSLF neurons. Our results inspire future studies to determine whether tissue or nerve injury downregulates channels that contribute to A-currents, thus potentially unmasking T-type calcium channel activity and membrane hyperexcitability in Y1-INs, leading to persistent pain. KEYPOINTSO_LINeuropeptide Y Y1 receptor-expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain. C_LIO_LIFor the first time, we characterized the firing patterns of Y1-expressing neurons in Y1eGFP reporter mice. C_LIO_LIUnder hyperpolarized conditions, most Y1eGFP neurons exhibited fast A-type potassium currents and delayed, short-latency firing (DSLF). C_LIO_LIY1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T-type calcium channels. C_LIO_LIThese results inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A-currents, thus unmasking membrane hyperexcitability in Y1- expressing dorsal horn neurons, leading to persistent pain C_LI

neuroscience↗