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  1. Article ; Online: When Differential Descending Control of Speed Matters: Descending Modulation of A- versus C-Fiber Evoked Spinal Nociception.

    Lumb, Bridget M / Donaldson, Lucy F

    Frontiers in pain research (Lausanne, Switzerland)

    2022  Volume 3, Page(s) 910471

    Abstract: Descending pain modulatory systems (DPMS) that originate within the brain and act to modulate spinal nociceptive transmission are a major determinant of the acute and chronic pain experience. Investigations of these systems in basic scientific research ... ...

    Abstract Descending pain modulatory systems (DPMS) that originate within the brain and act to modulate spinal nociceptive transmission are a major determinant of the acute and chronic pain experience. Investigations of these systems in basic scientific research is critical to the development of therapeutic strategies for the relief of pain. Despite our best efforts, something is lost in translation. This article will explore whether this is due in part to a primary focus on sensory modality leading to a failure to differentiate between descending control of A- vs. C-fiber mediated spinal nociception.
    Language English
    Publishing date 2022-06-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2673-561X
    ISSN (online) 2673-561X
    DOI 10.3389/fpain.2022.910471
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  2. Article ; Online: Editorial: Plasticity of Endogenous Pain Modulatory Circuits in Neuropathy.

    Patel, Ryan / Lumb, Bridget M / Bannister, Kirsty

    Frontiers in pain research (Lausanne, Switzerland)

    2021  Volume 2, Page(s) 776948

    Language English
    Publishing date 2021-10-21
    Publishing country Switzerland
    Document type Editorial
    ISSN 2673-561X
    ISSN (online) 2673-561X
    DOI 10.3389/fpain.2021.776948
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  3. Article: Dynamic causal modeling reveals increased cerebellar- periaqueductal gray communication during fear extinction.

    Paci, Elena / Lumb, Bridget M / Apps, Richard / Lawrenson, Charlotte L / Moran, Rosalyn J

    Frontiers in systems neuroscience

    2023  Volume 17, Page(s) 1148604

    Abstract: Introduction: The extinction of fear memories is an important component in regulating defensive behaviors, contributing toward adaptive processes essential for survival. The cerebellar medial nucleus (MCN) has bidirectional connections with the ... ...

    Abstract Introduction: The extinction of fear memories is an important component in regulating defensive behaviors, contributing toward adaptive processes essential for survival. The cerebellar medial nucleus (MCN) has bidirectional connections with the ventrolateral periaqueductal gray (vlPAG) and is implicated in the regulation of multiple aspects of fear, such as conditioned fear learning and the expression of defensive motor outputs. However, it is unclear how communication between the MCN and vlPAG changes during conditioned fear extinction.
    Methods: We use dynamic causal models (DCMs) to infer effective connectivity between the MCN and vlPAG during auditory cue-conditioned fear retrieval and extinction in the rat. DCMs determine causal relationships between neuronal sources by using neurobiologically motivated models to reproduce the dynamics of post-synaptic potentials generated by synaptic connections within and between brain regions. Auditory event related potentials (ERPs) during the conditioned tone offset were recorded simultaneously from MCN and vlPAG and then modeled to identify changes in the strength of the synaptic inputs between these brain areas and the relationship to freezing behavior across extinction trials. The DCMs were structured to model evoked responses to best represent conditioned tone offset ERPs and were adapted to represent PAG and cerebellar circuitry.
    Results: With the use of Parametric Empirical Bayesian (PEB) analysis we found that the strength of the information flow, mediated through enhanced synaptic efficacy from MCN to vlPAG was inversely related to freezing during extinction, i.e., communication from MCN to vlPAG increased with extinction.
    Discussion: The results are consistent with the cerebellum contributing to predictive processes that underpin fear extinction.
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2453005-0
    ISSN 1662-5137
    ISSN 1662-5137
    DOI 10.3389/fnsys.2023.1148604
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  4. Article ; Online: Top-down control of pain.

    Donaldson, Lucy F / Lumb, Bridget M

    The Journal of physiology

    2017  Volume 595, Issue 13, Page(s) 4139–4140

    MeSH term(s) Humans ; Pain ; Periaqueductal Gray
    Language English
    Publishing date 2017-06-28
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP273361
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  5. Article ; Online: Descending controls: how to harness for the relief of pain?

    Lumb, Bridget M

    The Journal of physiology

    2014  Volume 592, Issue 19, Page(s) 4097

    MeSH term(s) Animals ; Male ; Muscle, Skeletal/physiology ; Neural Inhibition/physiology ; Nociception/physiology ; Pain/physiopathology ; Receptors, Opioid/physiology
    Chemical Substances Receptors, Opioid
    Language English
    Publishing date 2014-09-30
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2014.280750
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  6. Article ; Online: The partial saphenous nerve injury model of pain impairs reward-related learning but not reward sensitivity or motivation.

    Phelps, Caroline E / Lumb, Bridget M / Donaldson, Lucy F / Robinson, Emma S

    Pain

    2021  Volume 162, Issue 3, Page(s) 956–966

    Abstract: Abstract: Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated ... ...

    Abstract Abstract: Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.
    MeSH term(s) Animals ; Depressive Disorder, Major ; Learning ; Motivation ; Pain/etiology ; Rats ; Reward
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002177
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  7. Article ; Online: Cerebellar modulation of memory encoding in the periaqueductal grey and fear behaviour.

    Lawrenson, Charlotte / Paci, Elena / Pickford, Jasmine / Drake, Robert A R / Lumb, Bridget M / Apps, Richard

    eLife

    2022  Volume 11

    Abstract: The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in male rat ventrolateral PAG (vlPAG) that encode fear memory through signalling the onset and offset of an auditory-conditioned stimulus ... ...

    Abstract The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in male rat ventrolateral PAG (vlPAG) that encode fear memory through signalling the onset and offset of an auditory-conditioned stimulus during presentation of the unreinforced conditioned tone (CS+) during retrieval. Some units only display CS+ onset or offset responses, and the two signals differ in extinction sensitivity, suggesting that they are independent of each other. In addition, understanding cerebellar contributions to survival circuits is advanced by the discovery that (i) reversible inactivation of the medial cerebellar nucleus (MCN) during fear consolidation leads in subsequent retrieval to (a) disruption of the temporal precision of vlPAG offset, but not onset responses to CS+, and (b) an increase in duration of freezing behaviour. And (ii) chemogenetic manipulation of the MCN-vlPAG projection during fear acquisition (a) reduces the occurrence of fear-related ultrasonic vocalisations, and (b) during subsequent retrieval, slows the extinction rate of fear-related freezing. These findings show that the cerebellum is part of the survival network that regulates fear memory processes at multiple timescales and in multiple ways, raising the possibility that dysfunctional interactions in the cerebellar-survival network may underlie fear-related disorders and comorbidities.
    MeSH term(s) Animals ; Cerebellum/physiology ; Conditioning, Classical/physiology ; Conditioning, Operant/physiology ; Fear/physiology ; Male ; Periaqueductal Gray/physiology ; Rats
    Language English
    Publishing date 2022-03-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.76278
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  8. Article ; Online: Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats.

    Drake, Robert Ar / Steel, Kenneth A / Apps, Richard / Lumb, Bridget M / Pickering, Anthony E

    eLife

    2021  Volume 10

    Abstract: The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the ...

    Abstract The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemogenetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.
    MeSH term(s) Animals ; Humans ; Male ; Neuralgia/physiopathology ; Neurons/cytology ; Olfactory Cortex/physiopathology ; Pain Threshold ; Periaqueductal Gray/cytology ; Periaqueductal Gray/physiopathology ; Rats ; Rats, Wistar ; Spinal Cord Dorsal Horn/physiopathology
    Language English
    Publishing date 2021-02-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.65156
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  9. Article ; Online: Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats

    Robert AR Drake / Kenneth A Steel / Richard Apps / Bridget M Lumb / Anthony E Pickering

    eLife, Vol

    2021  Volume 10

    Abstract: The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the ...

    Abstract The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemogenetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.
    Keywords pain ; prefrontal cortex ; descending pain modulation ; periaquductal gray ; neuropathic ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Top down control of spinal sensorimotor circuits essential for survival.

    Koutsikou, Stella / Apps, Richard / Lumb, Bridget M

    The Journal of physiology

    2017  Volume 595, Issue 13, Page(s) 4151–4158

    Abstract: The ability to interact with challenging environments requires coordination of sensory and motor systems that underpin appropriate survival behaviours. All animals, including humans, use active and passive coping strategies to react to escapable or ... ...

    Abstract The ability to interact with challenging environments requires coordination of sensory and motor systems that underpin appropriate survival behaviours. All animals, including humans, use active and passive coping strategies to react to escapable or inescapable threats, respectively. Across species the neural pathways involved in survival behaviours are highly conserved and there is a consensus that knowledge of such pathways is a fundamental step towards understanding the neural circuits underpinning emotion in humans and treating anxiety or other prevalent emotional disorders. The midbrain periaqueductal grey (PAG) lies at the heart of the defence-arousal system and its integrity is paramount to the expression of survival behaviours. To date, studies of 'top down control' components of defence behaviours have focused largely on the sensory and autonomic consequences of PAG activation. In this context, effects on motor activity have received comparatively little attention, despite overwhelming evidence of a pivotal role for the PAG in coordinating motor responses essential to survival (e.g. such as freezing in response to fear). In this article we provide an overview of top down control of sensory functions from the PAG, including selective control of different modalities of sensory, including proprioceptive, information forwarded to a major supsraspinal motor control centre, the cerebellum. Next, evidence from our own and other laboratories of PAG control of motor outflow is also discussed. Finally, the integration of sensorimotor functions by the PAG is considered, as part of coordinated defence behaviours that prepare an animal to be ready and able to react to danger.
    MeSH term(s) Animals ; Feedback, Physiological ; Humans ; Periaqueductal Gray/physiology ; Pyramidal Tracts/physiology
    Language English
    Publishing date 2017-04-24
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP273360
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