Chapter 18 Plasticity of the nervous system at the systemic, cellular and molecular levels: a mechanism of chronic pain and hyperalgesia

Author(s):  
M. Zimmermann ◽  
T. Herdegen
Keyword(s):  
2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.


2019 ◽  
Vol 20 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Marzia Malcangio

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.


2021 ◽  
Author(s):  
Esther Benedetti ◽  
James Burnett ◽  
Meredith Degnan ◽  
Danielle Horne ◽  
Andres Missair ◽  
...  

The neuronal, chemical, and electrical transmission of pain is a complex and intricate subject that continues to be studied and expounded. This review discusses the relevant physiology and influential factors contributing to the experience and subjective variation in a variety of acute and chronic pain presentations. This review contains 4 figures, 4 tables, and 30 references Keywords: acute pain, chronic pain, somatic pain, neuropathic pain, visceral pain, nociception, pain perception, gender-related pain, cancer pain, spine pain


Author(s):  
Maksim Vladimirovich Shpagin ◽  
Mikhail Valerievich Kolesnikov ◽  
Olga Yurievna Khutorskaya ◽  
Dmitriy Evgenievich Timoshkin ◽  
Artem Andreevich Belikin ◽  
...  

From the informational and structural point of view, the chronicity of pain is associated with the migration of nociogenic zones. The phenomenon of migration is based on the mechanisms of neuroplasticity, compensatory-restorative processes in the nervous system. On the basis of the phenomenon of migration of the nociogenic zone, a system of regional integrative therapy of chronic pain syndrome has been developed. Recommendations on the advisability of invasive shutdown of the nociogenic zone using invasive pharmacotherapy or surgical denervation have been proposed. In the course of studying the characteristics of chronic pain, depending on the duration of the disease, a direct proportional correlation was revealed between the increase in the components of pain and the duration of the pain syndrome, which can be explained by the increase in the number of nociogenic structures that form the complexity and stability of the pain syndrome. Thus, the necessity of neurodestructive interventions increases for attaining positive results. An important area of therapy is the inclusion of psychotherapy, pharmacotherapy and neuromodulation into the system of regional-integrative influence.


2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Raj Kumar

Botulinum toxin is one of the most potent molecule known to mankind. A neurotoxin, with high affinity for cholinergic synapse, is effectively capable of inhibiting the release of acetylcholine. On the other hand, botulinum toxin is therapeutically used for several musculoskeletal disorders. Although most of the therapeutic effect of botulinum toxin is due to temporary skeletal muscle relaxation (mainly due to inhibition of the acetylcholine release), other effects on the nervous system are also investigated. One of the therapeutically investigated areas of the botulinum neurotoxin (BoNT) is the treatment of pain. At present, it is used for several chronic pain diseases, such as myofascial syndrome, headaches, arthritis, and neuropathic pain. Although the effect of botulinum toxin in pain is mainly due to its effect on cholinergic transmission in the somatic and autonomic nervous systems, research suggests that botulinum toxin can also provide benefits related to effects on cholinergic control of cholinergic nociceptive and antinociceptive systems. Furthermore, evidence suggests that botulinum toxin can also affect central nervous system (CNS). In summary, botulinum toxin holds great potential for pain treatments. It may be also useful for the pain treatments where other methods are ineffective with no side effect(s). Further studies will establish the exact analgesic mechanisms, efficacy, and complication of botulinum toxin in chronic pain disorders, and to some extent acute pain disorders.


1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.


Author(s):  
Sumit Raosaheb Patil

ABSTRACT Ayurveda says Nidra yuktam Sukham Dukkham, In fact, it says that sleep is one of the three pillars of health. Insomnia or Nidranasha, is not just about being not getting proper sleep but it means that the nervous system has been weakened and reduces our ability to cope up with daily sleep. Insomnia is named as Nidranasha, happens due to vitiation of Kapha, Pitta and Vata dosha. Proper and deep sleep helps the person keep Energetic, Enthusiastic, does Brumhana, increases the Bala, increases vigour and vitality and most it keeps the Mind in stable state for gaining knowledge. Insomnia means inability to get sleep at night or inability to have a restful and sound sleep. Insomnia is typically followed by daytime sleepiness, low energy, irritability, and a depressed mood. Insomnia can be short term, lasting for days or weeks, or long term, lasting more than a month. Insomnia can occur independently or as a result of another problem. Conditions that can result in insomnia include psychological stress, chronic pain, heart failure, hyperthyroidism, heartburn, Alzheimer’s disease and Parkinson’s disease, Arthritis, menopause, and certain medications, and drugs such as caffeine, nicotine, and alcohol. Treatment of Insomnia:- Panchakarma â€“ Taila dhara a type of Shirodhara is very much useful in combacting the Insomnia caused due to various above said disorders. So its a demand of time to know about the real sleep and the disturbed sleep according to Ayurveda and Mordern medicines also and effect of Taila Dhara Brahmi,Jatamamsi siddha) in treating Insomnia.


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