scholarly journals Pain Perception and Response: Central Nervous System Mechanisms

Author(s):  
Arthur J. Hudson

ABSTRACT:Although several decades of studies have detailed peripheral and ascending nociceptive pathways to the thalamus and cerebral cortex, pain is a symptom that has remained difficult to characterize anatomically and physiologically. Positron emission tomography (PET) and functional magnetic imaging (fMRI) have recently demonstrated a number of cerebral and brain stem loci responding to cutaneous noxious stimuli. However, intersubject variability, both in the frequency and increased or decreased intensity of the responses, has caused uncertainty as to their significance. Nevertheless, the large number of available imaging studies have shown that many areas with recognized functions are frequently affected by painful stimuli. With this evidence and recent developments in tracing central nervous system connections between areas responding to noxious stimuli, it is possible to identify nociceptive pathways that are within, or contribute to, afferent spinothalamo-cortical sensory and efferent skeletomotor and autonomic motor systems. In this study it is proposed that cortical and nuclear mechanisms for pain perception and response are hierarchically arranged with the prefrontal cortex at its highest level. Nevertheless, all components make particular contributions without which certain nociceptive failures can occur, as in pathological pain arising in some cases of nervous system injury.

2018 ◽  
Vol 25 (26) ◽  
pp. 3096-3104 ◽  
Author(s):  
Daniele Mauro ◽  
Gaetano Barbagallo ◽  
Salvatore D`Angelo ◽  
Pasqualina Sannino ◽  
Saverio Naty ◽  
...  

In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography [PET]. The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography [CT] or magnetic resonance imaging[MRI] in order to improve spatial resolution. Early preclinical studies suggested that 18F–FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction. Neurological involvement is a distinct feature of various systemic autoimmune diseases, i.e. Systemic Lupus Erythematosus [SLE] or Behcet’s disease [BD]. Although MRI is largely considered the gold-standard imaging technique for the detection of Central Nervous System [CNS] involvement in these disorders. Several patients complain of neuropsychiatric symptoms [headache, epilepsy, anxiety or depression] in the absence of any significant MRI finding; in such patients the diagnosis relies mainly on clinical examination and often the role of the disease process versus iatrogenic or reactive forms is doubtful. The aim of this review is to explore the state-of-the-art for the role of PET imaging in CNS involvement in systemic rheumatic diseases. In addition, we explore the potential role of emerging radiopharmaceutical and their possible application in aiding the diagnosis of CNS involvement in systemic autoimmune diseases.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1778
Author(s):  
Pakhuri Mehta ◽  
Przemysław Miszta ◽  
Sławomir Filipek

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.


2019 ◽  
Vol 116 (23) ◽  
pp. 11402-11407 ◽  
Author(s):  
Tom Haywood ◽  
Corinne Beinat ◽  
Gayatri Gowrishankar ◽  
Chirag B. Patel ◽  
Israt S. Alam ◽  
...  

There is a growing need for monitoring or imaging gene therapy in the central nervous system (CNS). This can be achieved with a positron emission tomography (PET) reporter gene strategy. Here we report the development of a PET reporter gene system using the PKM2 gene with its associated radiotracer [18F]DASA-23. The PKM2 reporter gene was delivered to the brains of mice by adeno-associated virus (AAV9) via stereotactic injection. Serial PET imaging was carried out over 8 wk to assess PKM2 expression. After 8 wk, the brains were excised for further mRNA and protein analysis. PET imaging at 8 wk post-AAV delivery showed an increase in [18F]DASA-23 brain uptake in the transduced site of mice injected with the AAV mice over all controls. We believe PKM2 shows great promise as a PET reporter gene and to date is the only example that can be used in all areas of the CNS without breaking the blood–brain barrier, to monitor gene and cell therapy.


e-Neuroforum ◽  
2017 ◽  
Vol 23 (3) ◽  
Author(s):  
Alexander Groh ◽  
Rebecca Mease ◽  
Patrik Krieger

AbstractThe transduction of painful stimuli into the experience of pain involves several peripheral and central signaling pathways of the nervous system. The organization of these pathways parallels the main functions of pain: the assessment of noxious stimuli (where, what, how strong), and the negative emotion of unpleasantness. Multiple lines of evidence suggest that the thalamocortical (TC) system, which interprets ascending pain signals, has two main pathways which support these functions. We discuss the structural and functional findings that support the view that the lateral TC pathway is involved in discriminative assessment of pain, while the medial TC pathway gives rise to aversive emotions associated with pain. Our review focuses on acute pain, but we also discuss putative TC maladaptations in humans and animal models of pain that are thought to underlie pathological pain sensations.


2021 ◽  
pp. 014556132110489
Author(s):  
Xiangming Meng ◽  
Yuandan Pan

Objectives The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant characteristics of COVID-19 with a high prevalence. However, many aspects of COVID-19-induced anosmia are still far from being fully understood. The purpose of this review is to summarize recent developments in COVID-19-induced anosmia to increase awareness of the condition. Methods A literature search was carried out using the PubMed, Embase, Web of Science, and Scopus. We reviewed the latest literature on COVID-19-induced anosmia, including mechanisms of pathogenesis, olfactory testing, anosmia as predictive tool, pathological examinations, imaging findings, affected factors, co-existing diseases, treatments, prognosis, hypothesis theories, and future directions. Results The possible pathogenesis of COVID-19-induced anosmia may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The D614G spike variant may also play a role in the increased number of anosmia patients. Anosmia may also be an essential indicator of COVID-19 spread and an early indicator of the effectiveness of political decisions. The occurrence and development of COVID-19-induced anosmia may be influenced by smoking behaviors and underlying diseases such as type 2 diabetes, gastroesophageal disorders, and rhinitis. Most patients with COVID-19-induced anosmia can fully or partially recover their olfactory function for varying durations. COVID-19-induced anosmia can be treated with various approaches such as glucocorticoids and olfactory training. Conclusion Anosmia is one of the main features of COVID-19 and the underlying disease of the patient may also influence its occurrence and development. The possible pathogenesis of COVID-19-induced anosmia is very complicated, which may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system.


2011 ◽  
Vol 69 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Bruno Stankoff ◽  
Leorah Freeman ◽  
Marie-Stéphane Aigrot ◽  
Audrey Chardain ◽  
Frédéric Dollé ◽  
...  

Author(s):  
Orla Moriarty ◽  
Suellen M. Walker

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.


Author(s):  
Suellen M. Walker

Nociceptive pathways are functional following birth and acute responses to noxious stimuli have been documented from early development in both clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example the development of central sensitization, is well established (Woolf, 2011). However, the developing nervous system has additional susceptibilities to alterations in neural activity, and increases due to pain and injury in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. The impact of early pain and injury cannot be simply viewed as increasing or decreasing sensitivity as results vary depending on the type and severity of injury and the outcomes used for assessment. Laboratory studies allow evaluation of different forms of injury, potential confounding factors, underlying mechanisms, and potential for modulation by analgesia.


2020 ◽  
Vol 11 (1) ◽  
pp. 28-33
Author(s):  
Xixi Sheng ◽  
Mingwei Xu ◽  
Xia Li

AbstractPrimary central nervous system lymphoma (PCNSL) is rare. And the symptoms of PCNSL are atypical, it is extremely easy to be misdiagnosed as other diseases. However, early treatment is crucial which is requesting early diagnosis. We report a case of a 47-year-old man who was initially diagnosed as neuromyelitis optica (NMO) on the basis of clinical findings, slightly high Aquaporin4 (AQP4) (1:10) and high signals of magnetic resonance imaging. Though his symptoms progressively improved after steroid pulse treatment, but worse when steroid was decreased to 40 mg per day. We considered the patient should be diagnosed as PCNSL. After the examination of magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), the results indicated PCNSL was most possible. Therefore we gave him stereotactic biopsy of deep of supratentorial, which showed non-Hodgkin malignant B-cell lymphoma.


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