Pain pathophysiology and surgical management

2019 ◽  
pp. 895-908
Author(s):  
Richard Mannion ◽  
Rokas Tamasouskas
Keyword(s):  
Chronic Pain ◽  
Surgical Management ◽  
Surgical Procedures ◽  
Pain Mechanisms ◽  
Anatomy And Physiology ◽  
Peripheral Organs ◽  
Pain Pathways ◽  
Wide Range ◽  
Surgical Manipulation ◽  
The Brain

There can be no understanding of pain without an appreciation of its anatomical substrate from peripheral organs to the brain, but the notion of fixed pain pathways is long outdated. Plasticity, adaptive and maladaptive, has been described within each component and relay along the neuroaxis in a wide range of physiological and pathophysiological states. Clearly, this has implications for our understanding of the surgical manipulation of pain pathways and its utility (or otherwise) in patients. Here we provide an overview of the anatomy and physiology of nociception, discuss some of the pathophysiology of chronic pain states and relate this to surgical procedures that primarily aim to target pain mechanisms.

Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

2019 ◽  
pp. 816-832 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller
Keyword(s):  
Chronic Pain ◽  
Pain Response ◽  
Conscious Perception ◽  
Novel Therapies ◽  
The Past ◽  
Nociceptive Pathways ◽  
Pain Pathways ◽  
Technical Advances ◽  
The Brain

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.

FM1-2 A prospective study on surgical management of foot deformities in charcot marie tooth disease

2019 ◽  
Vol 90 (3) ◽  
pp. e21.2-e21
Author(s):  
M Laura ◽  
G Ramdharry ◽  
D Singh ◽  
D Kozyra ◽  
M Skorupinska ◽  
...  
Keyword(s):  
Surgical Management ◽  
Surgical Procedures ◽  
Ankle Instability ◽  
Evidence Base ◽  
Foot Deformities ◽  
Range Of Movement ◽  
Strength Assessment ◽  
Charcot Marie Tooth ◽  
Wide Range ◽  
Foot Alignment

ObjectivesCharcot-Marie-Tooth (CMT) Disease is the most common inherited peripheral neuropathy. Foot deformities are frequently observed in CMT patients and orthopaedic surgery is often required. Currently the evidence base on surgical management is limited. We prospectively studied surgical management of CMT patients attending our centre.SubjectsPatients were assessed at baseline and yearly after surgery.MethodsAssessment and data included: history of ankle instability, pain, skin condition, lower limb strength assessment, Charcot-Marie-Tooth Examination Score, Foot Posture Index, ankle dorsiflexion range of movement, questionnaires, details of surgical procedures.Results29 feet in 24 CMT patients (17 males, 7 females, mean age: 38.6±13) were evaluated prior to surgery. All patients but one had genetically confirmed CMT (18 CMT1A; 4 CMTX; 1 CMT4A). 17 feet in 12 pts were evaluated after 1 year; 10 feet in 9 pts were evaluated after 2 years; 8 feet in 7 pts were evaluated after 3 years. A wide range of surgical procedures were performed by one dedicated orthopaedic surgeon. There was significant improvement of foot alignment (p<0.001), callosities (p=0.002) and pain (p=0.022) after surgery. Surgery had no significant effect on strength, ankle range of movement, falls and fatigue.ConclusionsThe findings showed significant improvement of foot alignment, callosities and pain after surgery. Data acquired from this study will help developing orthopaedic intervention guidelines and identify areas for further research.

Surgical Management of Gout in the Foot and Ankle

2016 ◽  
Vol 106 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Daniel Poratt ◽  
Keith Rome
Keyword(s):  
Outcome Measures ◽  
Surgical Management ◽  
Surgical Procedures ◽  
Cochrane Library ◽  
Foot Pain ◽  
Foot And Ankle ◽  
Tophaceous Gout ◽  
Wide Range ◽  
Patient Reported

Background: The surgical management of tophaceous gout has been well documented in the literature, including its effect on foot pain and disability. To date, there have been no systematic reviews assessing the quality of the literature relating to the operative management of tophaceous gout and the outcomes in the foot and ankle. Methods: The following electronic databases were searched (1980–2014): Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Scopus, and the Cochrane Library. The articles identified were published in English and included adult participants (age ≥18 years) with diagnosed gout and surgical intervention to the foot and ankle. The Downs and Black Quality Index was modified to assess the quality of the articles being reviewed. Results: Six articles were reviewed and were of moderate quality (mean quality score of 71%). Surgical management was conducted on men (88%) with a mean age of 52 years. There was wide variation in the types of surgical procedures performed, with 28% of studies reporting surgery to the first metatarsophalangeal joint. Most studies were retrospective. A wide range of outcome measures were reported: foot pain, function, preoperative and postoperative activity levels, monitoring of uric acid levels, and patient satisfaction after surgery. Conclusions: The review demonstrated a limited number of good-quality studies. Several surgical procedures for the foot and ankle in people with chronic tophaceous gout were reported. Future studies should include prospective observational studies using validated and reliable patient-reported outcome measures.

Neurotransmitter systems of female mouse brain during growth of malignant melanoma modeled on the background of chronic pain

2018 ◽  
pp. 49-55
Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cerebral Cortex ◽  
Malignant Melanoma ◽  
Sciatic Nerve ◽  
Female Mouse ◽  
Combined Effects ◽  
Malignant Growth ◽  
Course Of Disease ◽  
The Brain ◽  
Melanoma Growth

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.

scholarly journals Adaptive mechanisms driving maladaptive pain: how chronic ongoing activity in primary nociceptors can enhance evolutionary fitness after severe injury

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190277 ◽  
Author(s):  
Edgar T. Walters
Keyword(s):  
Chronic Pain ◽  
Motor Impairment ◽  
Low Frequency ◽  
Severe Injury ◽  
Ongoing Activity ◽  
Pain Mechanisms ◽  
Bodily Injury ◽  
Adaptive Mechanisms ◽  
Survival And Reproduction ◽  
Ongoing Pain

Chronic pain is considered maladaptive by clinicians because it provides no apparent protective or recuperative benefits. Similarly, evolutionary speculations have assumed that chronic pain represents maladaptive or evolutionarily neutral dysregulation of acute pain mechanisms. By contrast, the present hypothesis proposes that chronic pain can be driven by mechanisms that evolved to reduce increased vulnerability to attack from predators and aggressive conspecifics, which often target prey showing physical impairment after severe injury. Ongoing pain and anxiety persisting long after severe injury continue to enhance vigilance and behavioural caution, decreasing the heightened vulnerability to attack that results from motor impairment and disfigurement, thereby increasing survival and reproduction (fitness). This hypothesis is supported by evidence of animals surviving and reproducing after traumatic amputations, and by complex specializations that enable primary nociceptors to detect local and systemic signs of injury and inflammation, and to maintain low-frequency discharge that can promote ongoing pain indefinitely. Ongoing activity in nociceptors involves intricate electrophysiological and anatomical specializations, including inducible alterations in the expression of ion channels and receptors that produce persistent hyperexcitability and hypersensitivity to chemical signals of injury. Clinically maladaptive chronic pain may sometimes result from the recruitment of this powerful evolutionary adaptation to severe bodily injury. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Weber-Adrian ◽  
Rikke Hahn Kofoed ◽  
Joseph Silburt ◽  
Zeinab Noroozian ◽  
Kairavi Shah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Intravenous Injection ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Fluorescent Protein ◽  
Gfp Expression ◽  
Peripheral Organs ◽  
Neuronal Expression ◽  
Green Fluorescent ◽  
The Brain

AbstractNon-surgical gene delivery to the brain can be achieved following intravenous injection of viral vectors coupled with transcranial MRI-guided focused ultrasound (MRIgFUS) to temporarily and locally permeabilize the blood–brain barrier. Vector and promoter selection can provide neuronal expression in the brain, while limiting biodistribution and expression in peripheral organs. To date, the biodistribution of adeno-associated viruses (AAVs) within peripheral organs had not been quantified following intravenous injection and MRIgFUS delivery to the brain. We evaluated the quantity of viral DNA from the serotypes AAV9, AAV6, and a mosaic AAV1&2, expressing green fluorescent protein (GFP) under the neuron-specific synapsin promoter (syn). AAVs were administered intravenously during MRIgFUS targeting to the striatum and hippocampus in mice. The syn promoter led to undetectable levels of GFP expression in peripheral organs. In the liver, the biodistribution of AAV9 and AAV1&2 was 12.9- and 4.4-fold higher, respectively, compared to AAV6. The percentage of GFP-positive neurons in the FUS-targeted areas of the brain was comparable for AAV6-syn-GFP and AAV1&2-syn-GFP. In summary, MRIgFUS-mediated gene delivery with AAV6-syn-GFP had lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.

scholarly journals Bio-Inspired Modality Fusion for Active Speaker Detection

2021 ◽  
Vol 11 (8) ◽  
pp. 3397
Author(s):  
Gustavo Assunção ◽  
Nuno Gonçalves ◽  
Paulo Menezes
Keyword(s):  
Superior Colliculus ◽  
Visual Information ◽  
Human Beings ◽  
Validation Process ◽  
Detection Approach ◽  
Wide Range ◽  
Speaker Detection ◽  
The One ◽  
The Brain ◽  
Fusion Ability

Human beings have developed fantastic abilities to integrate information from various sensory sources exploring their inherent complementarity. Perceptual capabilities are therefore heightened, enabling, for instance, the well-known "cocktail party" and McGurk effects, i.e., speech disambiguation from a panoply of sound signals. This fusion ability is also key in refining the perception of sound source location, as in distinguishing whose voice is being heard in a group conversation. Furthermore, neuroscience has successfully identified the superior colliculus region in the brain as the one responsible for this modality fusion, with a handful of biological models having been proposed to approach its underlying neurophysiological process. Deriving inspiration from one of these models, this paper presents a methodology for effectively fusing correlated auditory and visual information for active speaker detection. Such an ability can have a wide range of applications, from teleconferencing systems to social robotics. The detection approach initially routes auditory and visual information through two specialized neural network structures. The resulting embeddings are fused via a novel layer based on the superior colliculus, whose topological structure emulates spatial neuron cross-mapping of unimodal perceptual fields. The validation process employed two publicly available datasets, with achieved results confirming and greatly surpassing initial expectations.

scholarly journals Ostomy-Related Complications

2019 ◽  
Vol 32 (03) ◽  
pp. 176-182 ◽  
Author(s):  
Douglas Murken ◽  
Joshua Bleier
Keyword(s):  
Gastrointestinal Tract ◽  
Surgical Procedures ◽  
Parastomal Hernia ◽  
Significant Morbidity ◽  
Stoma Formation ◽  
Wide Range ◽  
Peristomal Skin ◽  
Stomal Stenosis

AbstractIleostomy or colostomy formation is an important component of many surgical procedures performed for a wide range of disorders of the gastrointestinal tract. Despite the frequency with which intestinal stomas are created, stoma-related complications remain common and are associated with significant morbidity as well as cost. Some of the most prevalent complications of stoma formation which will be detailed in this article include peristomal skin complications, retraction, stomal necrosis, stomal stenosis, prolapse, bleeding, dehydration from high ostomy output, and parastomal hernia. The authors will review these common complications, detail means to avoid or prevent them, and outline recommendations for management.

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