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Taylor, B. K.

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

3 recordsLinked to original sources
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↗