Development of Etoricoxib-Loaded Chitosan-and PEG-Based Microparticles to Restrain the Brain/Neuro Plasticity Associated Chronic Pain

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Shunmugaperumal Tamilvanan ◽  
Navjot Singh ◽  
Thenrajan Raja Sekharan
Keyword(s):  
Chronic Pain ◽  
The Brain

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.

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.

scholarly journals Optogenetics and photopharmacology in pain research and therapeutics

STEMedicine ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. e43 ◽  
Author(s):  
Federico Iseppon ◽  
Manuel Arcangeletti
Keyword(s):  
Chronic Pain ◽  
Pain Treatment ◽  
Molecular Switches ◽  
Genetic Profiling ◽  
Pain Research ◽  
Recent Advances ◽  
Cellular Components ◽  
The Brain

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.

Using magnetic resonance imaging to visualize the brain in chronic pain

Pain ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 1192-1193 ◽  
Author(s):  
Rachael L. Bosma ◽  
Kasey S. Hemington ◽  
Karen D. Davis
Keyword(s):  
Magnetic Resonance Imaging ◽  
Chronic Pain ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
The Brain

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.

Cortical Mechanisms for Emotional Fear and Chronic Pain

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Zhuo
Keyword(s):  
Chronic Pain ◽  
Emotional Disorders ◽  
Cortical Neurons ◽  
Neural Mechanism ◽  
Anterior Cingulate ◽  
Cellular Mechanisms ◽  
New Genes ◽  
Trace Fear ◽  
The Brain ◽  
Synaptic Model

Investigation of molecular and cellular mechanisms of synaptic plasticity is the major focus of many neuroscientists. There are two major reasons for searching new genes and molecules contributing to central plasticity: first, it provides basic neural mechanism for learning and memory, a key function of the brain; second, it provides new targets for treating brain-related disease. Here, I propose that LTP in the anterior cingulate cortex (ACC) as a synaptic model for emotional fear and chronic pain in the brain. Integrative approaches including genetic, neurobiological and physiological methods are used to investigate the roles of cortical neurons and microglia in synaptic LTP, fear and chronic pain. We have identified several key calcium-stimulated signaling molecules including AC1, CaMKIV and FMRP for AMPA receptor mediated cingulate LTP, trace fear memory, and chronic pain. By contrast, microglia only contributes to changes in spinal dorsal horn, but not in the cortex. Our findings strongly suggest that ACC LTP may serve as a cellular model for studying central sensitization that related to fear and chronic pain, as well as pain-related cognitive emotional disorders.

Increased Noradrenergic Neurotransmission to a Pain Facilitatory Area of the Brain Is Implicated in Facilitation of Chronic Pain

2015 ◽  
Vol 123 (3) ◽  
pp. 642-653 ◽  
Author(s):  
Isabel Martins ◽  
Paulina Carvalho ◽  
Martin G. de Vries ◽  
Armando Teixeira-Pinto ◽  
Steven P. Wilson ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Locus Coeruleus ◽  
Camp Response Element Binding ◽  
In Vivo Microdialysis ◽  
Reticular Nucleus ◽  
Analgesic Effects ◽  
Inhibitory Function ◽  
Noradrenaline Reuptake ◽  
The Brain

Abstract Background: Noradrenaline reuptake inhibitors are known to produce analgesia through a spinal action but they also act in the brain. However, the action of noradrenaline on supraspinal pain control regions is understudied. The authors addressed the noradrenergic modulation of the dorsal reticular nucleus (DRt), a medullary pronociceptive area, in the spared nerve injury (SNI) model of neuropathic pain. Methods: The expression of the phosphorylated cAMP response element-binding protein (pCREB), a marker of neuronal activation, was evaluated in the locus coeruleus and A5 noradrenergic neurons (n = 6 rats/group). pCREB was studied in noradrenergic DRt-projecting neurons retrogradely labeled in SNI animals (n = 3). In vivo microdialysis was used to measure noradrenaline release in the DRt on nociceptive stimulation or after DRt infusion of clonidine (n = 5 to 6 per group). Pharmacology, immunohistochemistry, and western blot were used to study α-adrenoreceptors in the DRt (n = 4 to 6 per group). Results: pCREB expression significantly increased in the locus coeruleus and A5 of SNI animals, and most noradrenergic DRt-projecting neurons expressed pCREB. In SNI animals, noradrenaline levels significantly increased on pinprick (mean ± SD, 126 ± 14%; P = 0.025 vs. baseline) and acetone stimulation (mean ± SD, 151 ± 12%; P < 0.001 vs. baseline), and clonidine infusion showed decreased α2-mediated inhibitory function. α1-adrenoreceptor blockade decreased nociceptive behavioral responses in SNI animals. α2-adrenoreceptor expression was not altered. Conclusions: Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord.

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