scholarly journals Pharmacologic Modulation of Noxious Stimulus-evoked Brain Activation in Cynomolgus Macaques Observed with Functional Neuroimaging

2020 ◽  
Vol 59 (1) ◽  
pp. 94-103
Author(s):  
Tomomi Shirai ◽  
Mizuho Yano ◽  
Takahiro Natsume ◽  
YūJi Awaga ◽  
Yoshitaka Itani ◽  
...  
Keyword(s):  
Pain Perception ◽  
Functional Neuroimaging ◽  
Analgesic Efficacy ◽  
Insular Cortex ◽  
Brain Activation ◽  
Noxious Stimulation ◽  
Invasive Procedures ◽  
Apparent Lack ◽  
Cynomolgus Macaques ◽  
The Brain

Maintaining effective analgesia during invasive procedures performed under general anesthesia is important for minimizing postoperative complications and ensuring satisfactory patient wellbeing and recovery. While patients under deep sedation may demonstrate an apparent lack of response to noxious stimulation, areas of the brain related to pain perception may still be activated. Thus, these patients may still experience pain during invasive procedures. The current study used anesthetized or sedated cynomolgus macaques and functional magnetic resonance imaging (fMRI) to assess the activation of the parts of the brain involved in pain perception during the application of peripheral noxious stimuli. Noxious pressure applied to the foot resulted in the bilateral activation of secondary somatosensory cortex (SII) and insular cortex (Ins), which are both involved in pain perception, in macaques under either propofol or pentobarbital sedation. No activation of SII/Ins was observed in macaques treated with either isoflurane or a combination of medetomidine, midazolam, and butorphanol. No movement or other reflexes were observed in response to noxious pressure during stimulation under anesthesia or sedation. The current findings show that despite the lack of visible behavioral symptoms of pain during anesthesia or sedation, brain activation suggests the presence of pain depending on the anesthetic agent used. These data suggest that fMRI could be used to noninvasively assess pain and to confirm the analgesic efficacy of currently used anesthetics. By assessing analgesic efficacy, researchers may refine their experiments, and design protocols that improve analgesia under anesthesia.

Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation

2015 ◽  
Vol 60 (1) ◽  
pp. 117-127 ◽  
Author(s):  
J. C. Choi ◽  
J. Kim ◽  
E. Kang ◽  
J.-H. Choi ◽  
W. Y. Park ◽  
...  
Keyword(s):  
Pain Perception ◽  
Brain Activation ◽  
Noxious Stimulation ◽  
Differential Effects ◽  
Step Down

scholarly journals Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Myeounghoon Cha ◽  
Songyeon Choi ◽  
Kyeongmin Kim ◽  
Bae Hwan Lee
Keyword(s):  
Chronic Pain ◽  
Nerve Injury ◽  
Pain Perception ◽  
Imaging Techniques ◽  
Insular Cortex ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Related Area ◽  
Mtor Inhibition ◽  
The Brain

AbstractNeuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

scholarly journals Pharmacological modulation of brain activation to non-noxious stimulation in a cynomolgus macaque model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110086
Author(s):  
Aldric Hama ◽  
Mizuho Yano ◽  
Wakana Sotogawa ◽  
Rintaro Fujii ◽  
Yuji Awaga ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Cynomolgus Macaque ◽  
Analgesic Efficacy ◽  
Brain Activation ◽  
Anterior Cingulate ◽  
Noxious Stimulation ◽  
Macaque Model ◽  
Injury Treatment ◽  
Stimulation Of

In vivo neuroimaging could be utilized as a noninvasive tool for elaborating the CNS mechanism of chronic pain and for elaborating mechanisms of potential analgesic therapeutics. A model of unilateral peripheral neuropathy was developed in the cynomolgus macaque, a species that is phylogenetically close to humans. Nerve entrapment was induced by placing a 4 mm length of polyvinyl cuff around the left common sciatic nerve. Prior to nerve injury, stimulation of the foot with a range of non-noxious von Frey filaments (1, 4, 8, 15, and 26 g) did not evoke brain activation as observed with functional magnetic resonance imaging (fMRI). Two weeks after injury, stimulation of the ipsilateral foot with non-noxious filaments activated the contralateral insula/secondary somatosensory cortex (Ins/SII) and anterior cingulate cortex (ACC). By contrast, no activation was observed with stimulation of the contralateral foot. Robust bilateral activation of thalamus was observed three to five weeks after nerve injury. Treatment with the clinical analgesic pregabalin reduced evoked activation of Ins/SII, thalamus and ACC whereas treatment with the NK1 receptor antagonist aprepitant reduced activation of the ipsilateral (left) thalamus. Twelve to 13 weeks after nerve injury, treatment with pregabalin reduced evoked activation of all regions of interest (ROI). By contrast, brain activation persisted in most ROI, except the ACC, following aprepitant treatment. Activation of the contralateral Ins/SII and bilateral thalamus was observed six months after nerve injury and pregabalin treatment suppressed activation of these nuclei. The current findings demonstrated persistent changes in CNS neurons following nerve injury as suggested by activation with non-painful mechanical stimulation. Furthermore, it was possible to functionally distinguish between a clinically efficacious analgesic drug, pregabalin, from a drug that has not demonstrated significant clinical analgesic efficacy, aprepitant. In vivo neuroimaging in the current nonhuman model could enhance translatability.

scholarly journals Utility of SPECT Functional Neuroimaging of Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammed Bermo ◽  
Mohammed Saqr ◽  
Hunter Hoffman ◽  
David Patterson ◽  
Sam Sharar ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Functional Neuroimaging ◽  
Brain Activity ◽  
Photon Emission ◽  
Brain Activation ◽  
Brain Perfusion ◽  
Functional Brain Imaging ◽  
Functional Brain ◽  
Clinical Scenarios ◽  
The Brain

Functional neuroimaging modalities vary in spatial and temporal resolution. One major limitation of most functional neuroimaging modalities is that only neural activation taking place inside the scanner can be imaged. This limitation makes functional neuroimaging in many clinical scenarios extremely difficult or impossible. The most commonly used radiopharmaceutical in Single Photon Emission Tomography (SPECT) functional brain imaging is Technetium 99 m-labeled Ethyl Cysteinate Dimer (ECD). ECD is a lipophilic compound with unique pharmacodynamics. It crosses the blood brain barrier and has high first pass extraction by the neurons proportional to regional brain perfusion at the time of injection. It reaches peak activity in the brain 1 min after injection and is then slowly cleared from the brain following a biexponential mode. This allows for a practical imaging window of 1 or 2 h after injection. In other words, it freezes a snapshot of brain perfusion at the time of injection that is kept and can be imaged later. This unique feature allows for designing functional brain imaging studies that do not require the patient to be inside the scanner at the time of brain activation. Functional brain imaging during severe burn wound care is an example that has been extensively studied using this technique. Not only does SPECT allow for imaging of brain activity under extreme pain conditions in clinical settings, but it also allows for imaging of brain activity modulation in response to analgesic maneuvers whether pharmacologic or non-traditional such as using virtual reality analgesia. Together with its utility in extreme situations, SPECTS is also helpful in investigating brain activation under typical pain conditions such as experimental controlled pain and chronic pain syndromes.

Seeing the Joe Miller

At Fault ◽  
2018 ◽  
pp. 178-202
Author(s):  
Sebastian D.G. Knowles
Keyword(s):  
Cognitive Function ◽  
Risk Taking ◽  
Pain Perception ◽  
Insular Cortex ◽  
The Brain

This chapter contains a study of the processes of neurology involved in humor detection and what those processes tell us about incongruity and risk-taking in the works of Joyce. A “Joe Miller” is a joke, and this study of Joyce’s jokes takes us into the heart of Joyce’s treasure hoard, which is language. Getting a joke is a cognitive function, performed in the same section of the brain where language tasks take place; appreciating a joke is an affective function, performed in the insular cortex, which is also implicated in pain perception, the perception of disgust, and vomiting. Both depend on parallax, or comparison with existing paradigms; the ability to think of two things at the same time is a useful way into the lexical world of Joyce.

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

scholarly journals Perceiving actions before they happen: psychological dimensions scaffold neural action prediction

2020 ◽  
Author(s):  
Mark A Thornton ◽  
Diana I Tamir
Keyword(s):  
Magnetic Resonance Imaging ◽  
Functional Neuroimaging ◽  
Social World ◽  
Action Space ◽  
Action Prediction ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
The Social ◽  
Psychological Dimensions ◽  
The Brain

Abstract The social world buzzes with action. People constantly walk, talk, eat, work, play, snooze and so on. To interact with others successfully, we need to both understand their current actions and predict their future actions. Here we used functional neuroimaging to test the hypothesis that people do both at the same time: when the brain perceives an action, it simultaneously encodes likely future actions. Specifically, we hypothesized that the brain represents perceived actions using a map that encodes which actions will occur next: the six-dimensional Abstraction, Creation, Tradition, Food(-relevance), Animacy and Spiritualism Taxonomy (ACT-FAST) action space. Within this space, the closer two actions are, the more likely they are to precede or follow each other. To test this hypothesis, participants watched a video featuring naturalistic sequences of actions while undergoing functional magnetic resonance imaging (fMRI) scanning. We first use a decoding model to demonstrate that the brain uses ACT-FAST to represent current actions. We then successfully predicted as-yet unseen actions, up to three actions into the future, based on their proximity to the current action’s coordinates in ACT-FAST space. This finding suggests that the brain represents actions using a six-dimensional action space that gives people an automatic glimpse of future actions.

Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fernanda R Marins ◽  
Aline C Oliveira ◽  
Fatimunnisa Qadri ◽  
Natalia Alenina ◽  
Michael Bader ◽  
...  
Keyword(s):  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Equimolar Dose ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

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