The Neurobiology of Pain Perception in Normal and Persistent Pain

Fenton, Bradford W.; Shih, Elim; Zolton, Jessica R.

doi:10.2217/pmt.15.27

Cited by 63 publications

(63 citation statements)

References 120 publications

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“…Collectively, studies in animal models suggest that enhanced pain states result from a shift in descending modulation to favor pain facilitation over inhibition, thus enhancing pain. Inhibition of RVM activity abolished enhanced nociceptive responses, including responses to stimuli applied to the dura . The role of descending pain modulation in central sensitization and migraine pain is elaborated further below.…”

Section: Trigeminal Neurovascular Systemmentioning

confidence: 99%

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CGRP and the Trigeminal System in Migraine

et al. 2019

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Objective The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system. Background Migraine is a prevalent and disabling neurological disease that is characterized in part by intense, throbbing, and unilateral headaches. Despite recent advances in understanding its pathophysiology, migraine still represents an unmet medical need, as it is often underrecognized and undertreated. Although CGRP has been known to play a pivotal role in migraine for the last 2 decades, this has now received more interest spurred by the early clinical successes of drugs that block CGRP signaling in the trigeminovascular system. Design This narrative review presents an update on the role of CGRP within the trigeminovascular system. PubMed searches were used to find recent (ie, 2016 to November 2018) published articles presenting new study results. Review articles are also included not as primary references but to bring these to the attention of the reader. Original research is referenced in describing the core of the narrative, and review articles are used to support ancillary points. Results The trigeminal ganglion neurons provide the connection between the periphery, stemming from the interface between the primary afferent fibers of the trigeminal ganglion and the meningeal vasculature and the central terminals in the trigeminal nucleus caudalis. The neuropeptide CGRP is abundant in trigeminal ganglion neurons, and is released from the peripheral nerve and central nerve terminals as well as being secreted within the trigeminal ganglion. Release of CGRP from the peripheral terminals initiates a cascade of events that include increased synthesis of nitric oxide and sensitization of the trigeminal nerves. Secreted CGRP in the trigeminal ganglion interacts with adjacent neurons and satellite glial cells to perpetuate peripheral sensitization, and can drive central sensitization of the second‐order neurons. A shift in central sensitization from activity‐dependent to activity‐independent central sensitization may indicate a mechanism driving the progression of episodic migraine to chronic migraine. The pathophysiology of cluster headache is much more obscure than that of migraine, but emerging evidence suggests that it may also involve hypersensitivity of the trigeminovascular system. Ongoing clinical studies with therapies targeted at CGRP will provide additional, valuable insights into the pathophysiology of this disorder. Conclusions CGRP plays an essential role in the pathophysiology of migraine. Treatments that interfere with the functioning of CGRP in the peripheral trigeminal system are effective against migraine. Blocking sensitization of the trigeminal nerve by attenuating CGRP activity in the periphery may be sufficient to block a migraine attack. Addit...

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Section: Trigeminal Neurovascular Systemmentioning

confidence: 99%

“…Inhibition of RVM activity abolished enhanced nociceptive responses, including responses to stimuli applied to the dura. [44][45][46][47] The role of descending pain modulation in central sensitization and migraine pain is elaborated further below.…”

Section: Trigeminal Neurovascular Systemmentioning

confidence: 99%

CGRP and the Trigeminal System in Migraine

et al. 2019

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“…The experience of pain is a result of complex interaction of cortical and subcortical regions (Garcia‐Larrea & Bastuji, 2018). OXT neurons project to key regions of the so called “pain matrix”, such as somatosensory and cingulate cortex, prefrontal regions, thalamus, insula and amygdala (Fenton, Shih, & Zolton, 2015). The pain matrix is characterized by a fluid network of brain regions involved in pain perception and processing, which are reciprocally modulated by internal states, affect, motivation and cognition (Garcia‐Larrea & Bastuji, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The primary matrix, including the somatosensory and cingulate cortex as well as posterior insula, and parietal operculum, provides information about the location of pain stimuli (Fenton et al, 2015). The secondary matrix comprising anterior cingulate cortex, anterior insula and amygdala controls attention on pain stimuli (Fenton et al, 2015). Eventually, the third matrix is involved in integrating information and generating a behavioural response.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin modulates intrinsic neural activity in patients with chronic low back pain

Schneider

Schmitgen

Boll

et al. 2020

European Journal of Pain

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Eur J Pain. 2020;24:945-955. | 945 wileyonlinelibrary.com/journal/ejpThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP). Methods: Twenty-four male patients with cLBP and 23 healthy males were examined using resting-state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 min before scanning. The fractional amplitude of low-frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT-effects on functional network strength. Results: Differential effects of OXT were observed in cLBP and healthy controls.FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group-specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus and right amygdala with pain-specific psychometric scores in cLBP. Conclusions: These data suggest OXT-related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT. Significance: Our data suggest significant oxytocin-related modulation of intrinsic regional activity and neural network strength in patients with chronic low back pain and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by oxytocin. Therapeutic effects of oxytocin for improved pain treatment need to be further investigated. K E Y W O R D S chronic pain, fALFF, MRI, multivariate analysis, resting state, source-based morphometry SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Schneider I, Schmitgen MM, Boll S, et al. Oxytocin modulates intrinsic neural activity in patients with chronic low back pain. Eur J Pain. 2020;24:945-955. https://doi.

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“…This pain-related brain network is generally regarded as the pain matrix. Bradford ( Fenton et al, 2015 ) classified the pain matrix into three different levels. The primary cortical pain matrix comprises S1, S2 ( Iannetti and Mouraux, 2010 ; Fomberstein et al, 2013 ), parietal operculum, and posterior insula (PI), and is responsible for the perception and location of pain.…”

Section: Pain Matrixmentioning

confidence: 99%

Neural Mechanisms With Respect to Different Paradigms and Relevant Regulatory Factors in Empathy for Pain

et al. 2018

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Empathy for pain is thought to activate the affective-motivational components of the pain matrix, which includes the anterior insula and middle and anterior cingulate cortices, as indicated by functional magnetic resonance imaging and other methodologies. Activity in this core neural network reflects the affective experience that activates our responses to pain and lays the neural foundation for our understanding of our own emotions and those of others. Furthermore, although picture-based paradigms can activate somatosensory components of directly experienced pain, cue-based paradigms cannot. In addition to this difference, the two paradigms evoke other distinct neuronal responses. Although the automatic “perception-action” model has long been the dominant theory for pain empathy, a “bottom-up, top-down” mechanism seems to be more comprehensive and persuasive. Indeed, a variety of factors can regulate the intensity of empathy for pain through “top-down” processes. In this paper, we integrate and generalize knowledge regarding pain empathy and introduce the findings from recent studies. We also present ideas for future research into the neural mechanisms underlying pain empathy.

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The Neurobiology of Pain Perception in Normal and Persistent Pain

Cited by 63 publications

References 120 publications

CGRP and the Trigeminal System in Migraine

CGRP and the Trigeminal System in Migraine

Oxytocin modulates intrinsic neural activity in patients with chronic low back pain

Neural Mechanisms With Respect to Different Paradigms and Relevant Regulatory Factors in Empathy for Pain

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