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Article ; Online: Challenges and opportunities for growing and retaining a pain research workforce.

Adams, Meredith C B / Wandner, Laura D / Kolber, Benedict J

2024

Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2015903-1
ISSN	1526-4637 ; 1526-2375
ISSN (online)	1526-4637
ISSN	1526-2375
DOI	10.1093/pm/pnae008
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Article ; Online: It's what's on the inside that counts: evidence for intracellular G-protein-coupled receptor signaling in inflammatory pain.

Kolber, Benedict J

Pain

2017 Volume 158, Issue 4, Page(s) 541–542

Language	English
Publishing date	2017-01-31
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000000843
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Article ; Online: Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons.

Hough, Andrea / Criswell, Connor / Faruk, Asef / Cavanaugh, Jane E / Kolber, Benedict J / Tidgewell, Kevin J

Marine drugs

2023 Volume 21, Issue 2

Abstract: Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from ... ...

Abstract	Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide's biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.
MeSH term(s)	Female ; Mice ; Animals ; Calcium/metabolism ; Sensory Receptor Cells ; Thiazoles/pharmacology ; Calcium Channel Blockers/pharmacology ; Calcium Signaling ; Mammals/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; barbamide ; Thiazoles ; Calcium Channel Blockers
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175190-0
ISSN	1660-3397 ; 1660-3397
ISSN (online)	1660-3397
ISSN	1660-3397
DOI	10.3390/md21020110
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Article ; Online: Developing a 3-D computational model of neurons in the central amygdala to understand pharmacological targets for pain.

Miller Neilan, Rachael / Reith, Carley / Anandan, Iniya / Kraeuter, Kayla / Allen, Heather N / Kolber, Benedict J

Frontiers in pain research (Lausanne, Switzerland)

2023 Volume 4, Page(s) 1183553

Abstract: Neuropathic and nociplastic pain are major causes of pain and involve brain areas such as the central nucleus of the amygdala (CeA). Within the CeA, neurons expressing protein kinase c-delta (PKCδ) or somatostatin (SST) have opposing roles in pain-like ... ...

Abstract	Neuropathic and nociplastic pain are major causes of pain and involve brain areas such as the central nucleus of the amygdala (CeA). Within the CeA, neurons expressing protein kinase c-delta (PKCδ) or somatostatin (SST) have opposing roles in pain-like modulation. In this manuscript, we describe our progress towards developing a 3-D computational model of PKCδ and SST neurons in the CeA and the use of this model to explore the pharmacological targeting of these two neural populations in modulating nociception. Our 3-D model expands upon our existing 2-D computational framework by including a realistic 3-D spatial representation of the CeA and its subnuclei and a network of directed links that preserves morphological properties of PKCδ and SST neurons. The model consists of 13,000 neurons with cell-type specific properties and behaviors estimated from laboratory data. During each model time step, neuron firing rates are updated based on an external stimulus, inhibitory signals are transmitted between neurons via the network, and a measure of nociceptive output from the CeA is calculated as the difference in firing rates of pro-nociceptive PKCδ neurons and anti-nociceptive SST neurons. Model simulations were conducted to explore differences in output for three different spatial distributions of PKCδ and SST neurons. Our results show that the localization of these neuron populations within CeA subnuclei is a key parameter in identifying spatial and cell-type pharmacological targets for pain.
Language	English
Publishing date	2023-05-30
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-561X
ISSN (online)	2673-561X
DOI	10.3389/fpain.2023.1183553
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Article ; Online: mGluRs head to toe in pain.

Kolber, Benedict J

Progress in molecular biology and translational science

2015 Volume 131, Page(s) 281–324

Abstract: Metabotropic glutamate receptors (mGluRs) and their role in modulating pain throughout the peripheral and central nervous system are the focus of this chapter. Because these receptors are so prolifically involved in pain signaling throughout the neuraxis, ...

Abstract	Metabotropic glutamate receptors (mGluRs) and their role in modulating pain throughout the peripheral and central nervous system are the focus of this chapter. Because these receptors are so prolifically involved in pain signaling throughout the neuraxis, we will use them as a vehicle to explore the totality of the neuraxis. These diverse receptors can increase or decrease pain depending on the subtype of receptor involved and anatomical location of activity. We will cover the basic molecular structure and function of mGluRs and then evaluate the role of different mGluRs at each level of the pain neuraxis. Similar to the functional anatomy involved in the processing of exogenous noxious stimuli, we will start from the peripheral nociceptive terminal and end in higher brain centers that are involved in the cognitive and emotional components of pain. We will conclude by examining the cutting-edge technology involved in the development of mGluR agents for the treatment of pain.
MeSH term(s)	Animals ; Brain/metabolism ; Drug Discovery ; Humans ; Models, Biological ; Pain/metabolism ; Receptors, Metabotropic Glutamate/metabolism ; Toes
Chemical Substances	Receptors, Metabotropic Glutamate
Language	English
Publishing date	2015
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2014.12.003
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Article ; Online: Left and right hemispheric lateralization of the amygdala in pain.

Allen, Heather N / Bobnar, Harley J / Kolber, Benedict J

Progress in neurobiology

2020 Volume 196, Page(s) 101891

Abstract: Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization of a brain structure, the amygdala, and how this lateralization is reshaping how we ... ...

Abstract	Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization of a brain structure, the amygdala, and how this lateralization is reshaping how we understand the role of the amygdala in pain processing. The amygdala is an almond-shaped, bilateral brain structure located within the limbic system. Historically, the amygdala was known to have a role in the processing of emotions and attaching emotional valence to memories and other experiences. The amygdala has been extensively studied in fear conditioning and affect but recently has been shown to have an important role in processing noxious information and impacting pain. The amygdala is composed of multiple nuclei; of special interest is the central nucleus of the amygdala (CeA). The CeA receives direct nociceptive inputs from the parabrachial nucleus (PBN) through the spino-parabrachio-amygdaloid pathway as well as more highly processed cortical and thalamic input via the lateral and basolateral amygdala. Although the amygdala is a bilateral brain region, most data investigating the amygdala's role in pain have been generated from the right CeA, which has an overwhelmingly pro-nociceptive function across pain models. The left CeA has often been characterized to have no effect on pain modulation, a dampened pro-nociceptive function, or most recently an anti-nociceptive function. This review explores the current literature on CeA lateralization and the hemispheres' respective roles in the processing and modulation of different forms of pain.
MeSH term(s)	Animals ; Arthralgia/physiopathology ; Central Amygdaloid Nucleus/physiopathology ; Functional Laterality/physiology ; Humans ; Neuralgia/physiopathology ; Nociceptive Pain/physiopathology ; Visceral Pain/physiopathology
Language	English
Publishing date	2020-07-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	185535-9
ISSN	1873-5118 ; 0301-0082
ISSN (online)	1873-5118
ISSN	0301-0082
DOI	10.1016/j.pneurobio.2020.101891
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Article ; Online: Design, synthesis, and biological evaluation of C

Kassick, Andrew J / Treat, Anny / Tomycz, Nestor / Feasel, Michael G / Kolber, Benedict J / Averick, Saadyah

RSC medicinal chemistry

2021 Volume 13, Issue 2, Page(s) 175–182

Abstract: The recent widespread abuse of high potency synthetic opioids, such as fentanyl, presents a serious threat to individuals affected by substance use disorder. Synthetic opioids generally exhibit ... ...

Abstract	The recent widespread abuse of high potency synthetic opioids, such as fentanyl, presents a serious threat to individuals affected by substance use disorder. Synthetic opioids generally exhibit prolonged
Language	English
Publishing date	2021-11-02
Publishing country	England
Document type	Journal Article
ISSN	2632-8682
ISSN (online)	2632-8682
DOI	10.1039/d1md00285f
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Article ; Online: Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons

Hough, Andrea / Criswell, Connor / Faruk, Asef / Cavanaugh, Jane E. / Kolber, Benedict J. / Tidgewell, Kevin J.

Mar Drugs. 2023 Feb. 02, v. 21, no. 2

2023

Abstract	Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.
Keywords	Cyanobacteria ; agonists ; calcium ; capsaicin ; dopamine ; drug development ; drugs ; females ; metabolites ; mice ; nociception ; sensory neurons ; toxicity ; transient receptor potential vanilloid channels ; transmembrane proteins
Language	English
Dates of publication	2023-0202
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2175190-0
ISSN	1660-3397
ISSN	1660-3397
DOI	10.3390/md21020110
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Visceral pressure stimulator for exploring hollow organ pain: a pilot study.

DeLong, Michael / Gil-Silva, Mauricio / Hong, Veronica Minsu / Babyok, Olivia / Kolber, Benedict J

Biomedical engineering online

2021 Volume 20, Issue 1, Page(s) 30

Abstract: Background: The regulation and control of pressure stimuli is useful for many studies of pain and nociception especially those in the visceral pain field. In many in vivo experiments, distinct air and liquid stimuli at varying pressures are delivered to ...

Abstract	Background: The regulation and control of pressure stimuli is useful for many studies of pain and nociception especially those in the visceral pain field. In many in vivo experiments, distinct air and liquid stimuli at varying pressures are delivered to hollow organs such as the bladder, vagina, and colon. These stimuli are coupled with behavioral, molecular, or physiological read-outs of the response to the stimulus. Care must be taken to deliver precise timed stimuli during experimentation. For example, stimuli signals can be used online to precisely time-lock the stimulus with a physiological output. Such precision requires the development of specialized hardware to control the stimulus (e.g., air) while providing a precise read-out of pressure and stimulus signal markers. Methods: In this study, we designed a timed pressure regulator [termed visceral pressure stimulator (VPS)] to control air flow, measure pressure (in mmHg), and send stimuli markers to online software. The device was built using a simple circuit and primarily off-the-shelf parts. A separate custom inline analog-to-digital pressure converter was used to validate the real pressure output of the VPS. Results: Using commercial physiological software (Spike2, CED), we were able to measure mouse bladder pressure continuously during delivery of unique air stimulus trials in a mouse while simultaneously recording an electromyogram (EMG) of the overlying abdominal muscles. Conclusions: This device will be useful for those who need to (1) deliver distinct pressure stimuli while (2) measuring the pressure in real-time and (3) monitoring stimulus on-off using physiological software.
MeSH term(s)	Animals ; Colon/diagnostic imaging ; Electromyography ; Female ; Mice ; Pilot Projects ; Pressure ; Signal Processing, Computer-Assisted ; Software ; Urinary Bladder/diagnostic imaging ; Vagina/diagnostic imaging ; Visceral Pain
Language	English
Publishing date	2021-03-25
Publishing country	England
Document type	Journal Article
ISSN	1475-925X
ISSN (online)	1475-925X
DOI	10.1186/s12938-021-00870-y
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Article ; Online: A Parabrachial-to-Amygdala Circuit That Determines Hemispheric Lateralization of Somatosensory Processing.

Allen, Heather N / Chaudhry, Sarah / Hong, Veronica M / Lewter, Lakeisha A / Sinha, Ghanshyam P / Carrasquillo, Yarimar / Taylor, Bradley K / Kolber, Benedict J

Biological psychiatry

2022 Volume 93, Issue 4, Page(s) 370–381

Abstract: Background: The central amygdala (CeA) is a bilateral hub of pain and emotional processing with well-established functional lateralization. We reported that optogenetic manipulation of neural activity in the left and right CeA has opposing effects on ... ...

Abstract	Background: The central amygdala (CeA) is a bilateral hub of pain and emotional processing with well-established functional lateralization. We reported that optogenetic manipulation of neural activity in the left and right CeA has opposing effects on bladder pain. Methods: To determine the influence of calcitonin gene-related peptide (CGRP) signaling from the parabrachial nucleus on this diametrically opposed lateralization, we administered CGRP and evaluated the activity of CeA neurons in acute brain slices as well as the behavioral signs of bladder pain in the mouse. Results: We found that CGRP increased firing in both the right and left CeA neurons. Furthermore, we found that CGRP administration in the right CeA increased behavioral signs of bladder pain and decreased bladder pain-like behavior when administered in the left CeA. Conclusions: These studies reveal a parabrachial-to-amygdala circuit driven by opposing actions of CGRP that determines hemispheric lateralization of visceral pain.
MeSH term(s)	Mice ; Animals ; Calcitonin Gene-Related Peptide/metabolism ; Pain ; Central Amygdaloid Nucleus/metabolism ; Neurons/physiology ; Emotions ; Parabrachial Nucleus/metabolism
Chemical Substances	Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2022.09.010
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