scholarly journals Brain Imaging Biomarkers for Chronic Pain

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhengwu Zhang ◽  
Jennifer S. Gewandter ◽  
Paul Geha

The prevalence of chronic pain has reached epidemic levels. In addition to personal suffering chronic pain is associated with psychiatric and medical co-morbidities, notably substance misuse, and a huge a societal cost amounting to hundreds of billions of dollars annually in medical cost, lost wages, and productivity. Chronic pain does not have a cure or quantitative diagnostic or prognostic tools. In this manuscript we provide evidence that this situation is about to change. We first start by summarizing our current understanding of the role of the brain in the pathogenesis of chronic pain. We particularly focus on the concept of learning in the emergence of chronic pain, and the implication of the limbic brain circuitry and dopaminergic signaling, which underly emotional learning and decision making, in this process. Next, we summarize data from our labs and from other groups on the latest brain imaging findings in different chronic pain conditions focusing on results with significant potential for translation into clinical applications. The gaps in the study of chronic pain and brain imaging are highlighted in throughout the overview. Finally, we conclude by discussing the costs and benefits of using brain biomarkers of chronic pain and compare to other potential markers.

Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jonathan Singer ◽  
Alyssa Conigliaro ◽  
Elizabeth Spina ◽  
Susan Law ◽  
Steven Levine

Background: Central Post Stroke Pain (CPSP) is reportedly due to strokes in the thalamic region (Dishinbition Theory); however, the Central Imbalance Theory states that CPSP is due to damage to the spinothalamic pathway (STP). Aims: 1) Clarify the role of thalamic strokes and STP damage in CPSP patients. 2) Gain a current understanding of anatomic substrates, brain imaging, and treatment of CPSP. Methods: Two independent reviewers systematically reviewed PUBMED, CINAHL and Web of Science for studies including original, clinical studies and randomized controlled trials (RCTs) using PRISMA guidelines. Studies had to assess CPSP, using a single question or pain scale. Results: Search from January – July 2016, identifying 731 publications. We extracted data from 23 studies and categorized the articles’ aims into 4 sections: somatosensory deficits (5 studies), STP (3 studies), brain imaging (7 studies), and RCTs (8 studies). Somatosensory studies showed high rates of CPSP; however, the underlying causes of these deficits were unclear. Most studies did not refer to stroke location as playing a role in CPSP, but that pathways may. STP studies displayed consistent evidence that the STP plays a major role in CPSP, delineating that CPSP can occur even when the stroke is not in the thalamic region but in other regions (e.g. cerebellum, basal ganglia, medulla). Four of the brain imaging studies found CPSP not related and 3 found it was related to thalamic strokes. All 7 studies had major limitations including sample size, no control groups, and selection bias. RCTs were mostly negative, but brain stem and motor cortex stimulation studies showed the most promise. Conclusions: While CPSP has been linked to the thalamic region since the early 1900’s, the peer-reviewed literature showed equivocal results when examining location of stroke. Our systematic review suggests damage to the STP is associated with CPSP and this could provide insights into mechanisms and treatment. Moreover, historical connection of strokes in the thalamic region and CPSP should be reevaluated as many studies noted that strokes in other regions of the brain also produce CPSP.


STEMedicine ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. e43 ◽  
Author(s):  
Federico Iseppon ◽  
Manuel Arcangeletti

Pain afflicts billions of people worldwide, who suffer especially from long-term chronic pain. This gruelling condition affects the nervous system at all levels: from the brain to the spinal cord, the Dorsal Root Ganglia (DRG) and the peripheral fibres innervating the skin. The nature of the different molecular and cellular components of the somatosensory modalities, as well as the complexity of the peripheral and central circuitry are yet poorly understood. Light-based techniques such as optogenetics, in concert with the recent advances in single-cell genetic profiling, can help to elucidate the role of diverse neuronal sub-populations in the encoding of different sensory and painful stimuli by switching these neurons on and off via optically active proteins, namely opsins.  Recently, photopharmacology has emerged from the efforts made to advance optogenetics. The introduction of azo-benzene-based light-sensitive molecular switches has been applied to a wide variety of molecular targets, from ion channels and receptors to transporters, enzymes and many more, some of which are paramount for pain research and therapy. In this Review, we summarise the recent advances in the fields of optogenetics and photopharmacology and we discuss the use of light-based techniques for the study of acute and chronic pain physiology, as well as their potential for future therapeutic use to improve pain treatment.


Reumatismo ◽  
2012 ◽  
Vol 64 (3) ◽  
Author(s):  
M. Capraro ◽  
M. Della Valle ◽  
M. Podswiadek ◽  
P. De Sandre ◽  
E. Sgnaolin ◽  
...  

Cephalalgia ◽  
2013 ◽  
Vol 33 (15) ◽  
pp. 1264-1268 ◽  
Author(s):  
Nouchine Hadjikhani ◽  
Noreen Ward ◽  
Jasmine Boshyan ◽  
Vitaly Napadow ◽  
Yumi Maeda ◽  
...  

Background Migraine is a neurovascular disorder in which altered functional connectivity between pain-modulating circuits and the limbic system may play a role. Cortical spreading depression (CSD), which underlies migraine aura (MWA), induces C-fos expression in the amygdala. The role of CSD and amygdala connectivity in migraine without aura (MwoA) is less clear and may differentiate migraine from other chronic pain disorders. Methods Using resting-state functional MRI, we compared functional connectivity between the amygdala and the cortex in MWA and MWoA patients as well as in healthy subjects and in two other chronic pain conditions not associated with CSD: trigeminal neuralgia (TGN) and carpal tunnel syndrome (CTS). Results Amygdala connectivity in both MWA and MWoA was increased to the visceroceptive insula relative to all other groups examined. Conclusion The observed increased connectivity within the limbic/viscerosensory network, present only in migraineurs, adds to the evidence of a neurolimbic pain network dysfunction and may reflect repetitive episodes of CSD leading to the development of migraine pain.


2017 ◽  
Vol 18 (7) ◽  
pp. 757-777 ◽  
Author(s):  
Shannon M. Smith ◽  
Robert H. Dworkin ◽  
Dennis C. Turk ◽  
Ralf Baron ◽  
Michael Polydefkis ◽  
...  

2010 ◽  
Vol 5 (3) ◽  
pp. 377-392 ◽  
Author(s):  
John D Salamone ◽  
Merce Correa ◽  
Andrew M Farrar ◽  
Eric J Nunes ◽  
Lyndsey E Collins

Dysphagia ◽  
2021 ◽  
Author(s):  
Ayodele Sasegbon ◽  
Shaheen Hamdy

AbstractSwallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The cerebellum is a critical part of the brain responsible for the modulation of movements. It receives input from motor cortical and sensory areas and fine tunes these inputs to produce coordinated motor outputs. With respect to swallowing, numerous functional imaging studies have demonstrated increased activity in the cerebellum during the task of swallowing and damage to the cerebellum following differing pathological processes is associated with dysphagia. Single pulses of transcranial magnetic stimulation (TMS) have been applied to the cerebellum and have been shown to evoke motor responses in the pharynx. Moreover, repetitive TMS (rTMS) over the cerebellum can modulate cerebral motor (pharyngeal) cortical activity. Neurostimulation has allowed a better understanding of the connections that exist between the cerebellum and cerebral swallowing motor areas in health and provides a potential treatment for neurogenic dysphagia in illness. In this review we will examine what is currently known about the role of the cerebellum in the control of swallowing, explore new findings from neurostimulatory and imaging studies and provide an overview of the future clinical applications of cerebellar stimulation for treating dysphagia.


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