Pain neurophysiology

2013 ◽  
Author(s):  
Hans-Georg Schaible ◽  
Rainer H. Straub
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Cell Activation ◽  
Warning Signal ◽  
Nociceptive Pain ◽  
Neural Function ◽  
Peripheral Sensitization ◽  
Nerve Fibres ◽  
Glial Cell Activation ◽  
Ectopic Discharges

Physiological pain is evoked by intense (noxious) stimuli acting on healthy tissue functioning as a warning signal to avoid damage of the tissue. In contrast, pathophysiological pain is present in the course of disease, and it is often elicited by low-intensity stimulation or occurs even as resting pain. Causes of pathophysiological pain are either inflammation or injury causing pathophysiological nociceptive pain or damage to nerve cells evoking neuropathic pain. The major peripheral neuronal mechanism of pathophysiological nociceptive pain is the sensitization of peripheral nociceptors for mechanical, thermal and chemical stimuli; the major peripheral mechanism of neuropathic pain is the generation of ectopic discharges in injured nerve fibres. These phenomena are created by changes of ion channels in the neurons, e.g. by the influence of inflammatory mediators or growth factors. Both peripheral sensitization and ectopic discharges can evoke the development of hyperexcitability of central nociceptive pathways, called central sensitization, which amplifies the nociceptive processing. Central sensitization is caused by changes of the synaptic processing, in which glial cell activation also plays an important role. Endogenous inhibitory neuronal systems may reduce pain but some types of pain are characterized by the loss of inhibitory neural function. In addition to their role in pain generation, nociceptive afferents and the spinal cord can further enhance the inflammatory process by the release of neuropeptides into the innervated tissue and by activation of sympathetic efferent fibres. However, in inflamed tissue the innervation is remodelled by repellent factors, in particular with a loss of sympathetic nerve fibres.

Pain neurophysiology

2013 ◽  
pp. 431-436
Author(s):  
Hans-Georg Schaible ◽  
Rainer H. Straub
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Cell Activation ◽  
Warning Signal ◽  
Nociceptive Pain ◽  
Neural Function ◽  
Nerve Fibres ◽  
Glial Cell Activation ◽  
Neuronal Systems ◽  
Ectopic Discharges

Physiological pain is evoked by intense (noxious) stimuli acting on healthy tissue functioning as a warning signal to avoid damage of the tissue. In contrast, pathophysiological pain is present in the course of disease, and it is often elicited by low-intensity stimulation or occurs even as resting pain. Causes of pathophysiological pain are either inflammation or injury causing pathophysiological nociceptive pain or damage to nerve cells evoking neuropathic pain. The major peripheral neuronal mechanism of pathophysiological nociceptive pain is the sensitization of peripheral nociceptors for mechanical, thermal and chemical stimuli; the major peripheral mechanism of neuropathic pain is the generation of ectopic discharges in injured nerve fibres. These phenomena are created by changes of ion channels in the neurons, e.g. by the influence of inflammatory mediators or growth factors. Both peripheral sensitization and ectopic discharges can evoke the development of hyperexcitability of central nociceptive pathways, called central sensitization, which amplifies the nociceptive processing. Central sensitization is caused by changes of the synaptic processing, in which glial cell activation also plays an important role. Endogenous inhibitory neuronal systems may reduce pain but some types of pain are characterized by the loss of inhibitory neural function. In addition to their role in pain generation, nociceptive afferents and the spinal cord can further enhance the inflammatory process by the release of neuropeptides into the innervated tissue and by activation of sympathetic efferent fibres. However, in inflamed tissue the innervation is remodelled by repellent factors, in particular with a loss of sympathetic nerve fibres.

The neural basis of chronic pain, its plasticity and modulation

1997 ◽  
Vol 20 (3) ◽  
pp. 435-437 ◽  
Author(s):  
Misha-Miroslav Backonja
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Central Sensitization ◽  
Primary Afferents ◽  
Peripheral Sensitization ◽  
Neural Basis ◽  
Painful Events

Dysfunction or injury of pain-transmitting primary afferents' central pathways can result in pain. The organism as a whole responds to such injury and consequently many symptoms of neuropathic pain develop. The nervous system responds to painful events and injury with neuroplasticity. Both peripheral sensitization and central sensitization take place and are mediated by a number of biochemical factors, including genes and receptors. Correction of altered receptors activity is the logical way to intervene therapeutically. [berkley; blumberg et al.; coderre & katz; dickenson; mcmahon; wiesenfeld-hallinet al.]

scholarly journals Pathophysiology of neuropathic pain

2021 ◽  
Vol 64 (7) ◽  
pp. 468-476
Author(s):  
Ohyun Kwon
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Research Progress ◽  
Diagnostic Tools ◽  
Afferent Neuron ◽  
Peripheral Sensitization ◽  
Best Management ◽  
Plausible Mechanism ◽  
Key Aspects ◽  
Inflammatory Milieu

Background: Neuropathic pain is notoriously difficult to manage properly, not only because of its varied nature and the absence of objective diagnostic tools but also because of extensive reciprocal neuronal interactive pathogenic mechanism from the molecular level to patient’s own psychophysical characteristics. This paper briefly reviews the pathophysiology of neuropathic pain to the level of clinicians’ interest and its potential in clinical practiceCurrent Concepts: Recent research progress now allows us to obtain a bird view of neuropathic pain pathophysiology: peripheral and central sensitization. For peripheral sensitization, a local inflammatory milieu of the injured nerve primarily drives sequential phenotypic changes, which are critical and shared by both neuropathic and inflammatory pain. Central sensitization is led either by the hyperexcitability of the second-order afferent neuron itself or loss of physiological inhibitory control of the transmission of pain signal to the higher nervous system. Peripheral and central sensitization work synergistically but can also introduce neuropathic pain alone.Discussion and Conclusion: The cause of neuropathic pain is diverse, and understanding of its pathophysiology is still insufficient to realize a mechanism-based approach to clinical phenotypes or therapeutic applications. In dealing with chronic neuropathic pain, it is highly desirable to assess key aspects of a patient’s pain based on a plausible mechanism and select the best management method accordingly.

scholarly journals The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain

2006 ◽  
Vol 2 (4) ◽  
pp. 279-291 ◽  
Author(s):  
Annemarie Ledeboer ◽  
Tongyao Liu ◽  
Jennifer A. Shumilla ◽  
John H. Mahoney ◽  
Sharmila Vijay ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Cell Activation ◽  
Therapeutic Agent ◽  
Chronic Constriction Injury ◽  
Phosphodiesterase Inhibitor ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Glial Cell Activation ◽  
Medical Need

AbstractControlling neuropathic pain is an unmet medical need and we set out to identify new therapeutic candidates. AV411 (ibudilast) is a relatively nonselective phosphodiesterase inhibitor that also suppresses glial-cell activation and can partition into the CNS. Recent data strongly implicate activated glial cells in the spinal cord in the development and maintenance of neuropathic pain. We hypothesized that AV411 might be effective in the treatment of neuropathic pain and, hence, tested whether it attenuates the mechanical allodynia induced in rats by chronic constriction injury (CCI) of the sciatic nerve, spinal nerve ligation (SNL) and the chemotherapeutic paclitaxel (Taxol¯). Twice-daily systemic administration of AV411 for multiple days resulted in a sustained attenuation of CCI-induced allodynia. Reversal of allodynia was of similar magnitude to that observed with gabapentin and enhanced efficacy was observed in combination. We further show that multi-day AV411 reduces SNL-induced allodynia, and reverses and prevents paclitaxel-induced allodynia. Also, AV411 cotreatment attenuates tolerance to morphine in nerve-injured rats. Safety pharmacology, pharmacokinetic and initial mechanistic analyses were also performed. Overall, the results indicate that AV411 is effective in diverse models of neuropathic pain and support further exploration of its potential as a therapeutic agent for the treatment of neuropathic pain.

Mechanisms of Neuropathic Pain

2018 ◽  
pp. 17-26
Author(s):  
Jianguo Cheng
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Receptive Fields ◽  
Somatosensory System ◽  
Direct Consequence ◽  
Inflammatory Cells ◽  
Peripheral Sensitization ◽  
Excitatory Pathways ◽  
Processing Pathways ◽  
The Central Nervous System

Neuropathic pain arises as a direct consequence of a lesion or a disease affecting the somatosensory system. The mechanisms of neuropathic pain are often complex and difficult to study given the diversity of causes, pathology, and clinical presentation of various neuropathic pain conditions. Common mechanisms include peripheral and central sensitizations. Peripheral sensitization refers to increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields. Central sensitization refers to the augmented response of central signaling neurons. The mechanisms of peripheral and central sensitization are understood at the cellular and molecular levels. The processes of neuroplasticity involve activation of inflammatory cells, such as macrophages (and microglia in the central nervous system) and other immune cells, and release of inflammatory mediators, such as cytokines, chemokines, and a host of other mediators. Interactions of these mediators with specific receptors in the nociceptors or the spinal cord neurons may lead to phosphorylation or changes in expression of ion channels, receptors, transporters, and other effectors through specific signaling pathways. These events ultimately lead to changes in excitability, conductivity, and transmissibility of neurons in the pain processing pathways. Other factors may include disinhibition of interneurons, changes in descending inhibitory and excitatory pathways, and reorganization of the cortical areas and their interconnections.

scholarly journals Progressive Increase of Inflammatory CXCR4 and TNF-Alpha in the Dorsal Root Ganglia and Spinal Cord Maintains Peripheral and Central Sensitization to Diabetic Neuropathic Pain in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Dan Zhu ◽  
Tingting Fan ◽  
Xinyue Huo ◽  
Jian Cui ◽  
Chi Wai Cheung ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglia ◽  
Central Sensitization ◽  
Dorsal Root ◽  
Diabetic Rats ◽  
Spinal Cord Dorsal Horn ◽  
Peripheral Sensitization ◽  
Diabetic Neuropathic Pain ◽  
Spinal Cord Dorsal

Diabetic neuropathic pain (DNP) is a common and serious complication of diabetic patients. The pathogenesis of DNP is largely unclear. The proinflammation proteins, CXCR4, and TNF-α play critical roles in the development of pain, while their relative roles in the development of DNP and especially its progression is unknown. We proposed that establishment of diabetic pain models in rodents and evaluating the stability of behavioral tests are necessary approaches to better understand the mechanism of DNP. In this study, Von Frey and Hargreaves Apparatus was used to analyze the behavioral changes of mechanical allodynia and heat hyperalgesia in streptozotocin-induced diabetic rats at different phases of diabetes. Moreover, CXCR4 and TNF-α of spinal cord dorsal and dorsal root ganglia (DRG) were detected by western blotting and immunostaining over time. The values of paw withdrawal threshold (PWT) and paw withdrawal latencies (PWL) were reduced as early as 1 week in diabetic rats and persistently maintained at lower levels during the progression of diabetes as compared to control rats that were concomitant with significant increases of both CXCR4 and TNF-α protein expressions in the DRG at 2 weeks and 5 weeks (the end of the experiments) of diabetes. By contrast, CXCR4 and TNF-α in the spinal cord dorsal horn did not significantly increase at 2 weeks of diabetes while both were significantly upregulated at 5 weeks of diabetes. The results indicate that central sensitization of spinal cord dorsal may result from persistent peripheral sensitization and suggest a potential reference for further treatment of DNP.

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