Neuroinflammation and Central Sensitization in Chronic and Widespread Pain

Anesthesiology, Год журнала: 2018, Номер 129(2), С. 343 - 366

Опубликована: Фев. 16, 2018

Abstract Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness pathways after painful insults. Accumulating evidence suggests that sensitization also driven neuroinflammation the peripheral nervous system. A characteristic feature activation glial cells, such as microglia astrocytes, spinal cord brain, leading to release proinflammatory cytokines chemokines. Recent studies suggest chemokines are powerful neuromodulators play sufficient role inducing hyperalgesia allodynia system administration. Sustained increase promotes chronic widespread affects multiple body sites. Thus, drives via sensitization. We discuss sex-dependent glial/immune signaling new therapeutic approaches control for resolution pain.

Язык: Английский

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Neuropathic Pain: From Mechanisms to Treatment

Physiological Reviews, Год журнала: 2020, Номер 101(1), С. 259 - 301

Опубликована: Июнь 25, 2020

Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is common chronic condition with major impact on quality life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic and central poststroke pain. Most patients complain an ongoing intermittent spontaneous of, for example, burning, pricking, squeezing quality, which may be accompanied evoked pain, particular to light touch cold. Ectopic activity in, nerve-end neuroma, compressed nerves nerve roots, dorsal root ganglia, thalamus in different conditions underlie Evoked spread neighboring areas, underlying pathophysiology involves peripheral sensitization. Maladaptive structural changes number cell-cell interactions molecular signaling sensitization nociceptive pathways. These alteration ion channels, activation immune cells, glial-derived mediators, epigenetic regulation. The classes therapeutics drugs acting α 2 δ subunits calcium sodium descending modulatory inhibitory

Язык: Английский

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Qualitative sex differences in pain processing: emerging evidence of a biased literature

Nature reviews. Neuroscience, Год журнала: 2020, Номер 21(7), С. 353 - 365

Опубликована: Май 21, 2020

Язык: Английский

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Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

Neuron, Год журнала: 2020, Номер 108(1), С. 128 - 144.e9

Опубликована: Авг. 17, 2020

Язык: Английский

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Inflammation in the pathophysiology of neuropathic pain

Pain, Год журнала: 2017, Номер 159(3), С. 595 - 602

Опубликована: Ноя. 25, 2017

Abstract Peripheral nerve injuries and diseases often lead to pain persisting beyond the resolution of damage, indicating an active disease-promoting process, which may result in chronic pain. This is regarded as a maladaptive mechanism resulting from neuroinflammation that originally serves promote regeneration healing. Knowledge on these physiological pathophysiological processes has accumulated over last few decades started yield potential therapeutic targets. Key players are macrophages, T-lymphocytes, cytokines, chemokines. In spinal cord brain, microglia astrocytes involved. Recently, data have been emerging regulation players. MicroRNAs other noncoding RNAs discussed master switches link injury, pain, inflammation. Clinical disorders most intensely studied context complex regional syndrome, polyneuropathies, postherpetic neuralgia, fibromyalgia recently neuropathic component described. Research several groups shown important role both proinflammatory anti-inflammatory cytokines states humans. There ample evidence analgesic action animal models. The interplay nociceptive system provides possibilities challenges concerning treatment strategies based this concept.

Язык: Английский

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Astrocytes in chronic pain and itch

Nature reviews. Neuroscience, Год журнала: 2019, Номер 20(11), С. 667 - 685

Опубликована: Сен. 19, 2019

Язык: Английский

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Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Янв. 14, 2020

Abstract Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation macrophages around injured sensory neurons in root ganglia (DRG). Here we demonstrate critical contribution DRG macrophages, but not those at site, to both initiation maintenance mechanical hypersensitivity that characterizes neuropathic pain phenotype. In contrast reported sexual dimorphism microglial pain, depletion reduces injury-induced male female mice. However, fewer are induced mice deletion colony-stimulating factor 1 from neurons, which prevents proliferation, only macrophage Finally, molecular cross-talk between axotomized revealing potential targets for management.

Язык: Английский

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The endometrial immune environment of women with endometriosis

Human Reproduction Update, Год журнала: 2019, Номер 25(5), С. 565 - 592

Опубликована: Апрель 20, 2019

Abstract BACKGROUND Endometriosis, a common oestrogen-dependent inflammatory disorder in women of reproductive age, is characterized by endometrial-like tissue outside its normal location the uterus, which causes pelvic scarring, pain and infertility. While pathogenesis poorly understood, immune system (systemically locally endometrium, endometriotic lesions peritoneal fluid) believed to play central role aetiology, pathophysiology associated morbidities pain, infertility poor pregnancy outcomes. However, cell populations within endometrium with disease have had incomplete phenotyping, thereby limiting insight into their roles this disorder. OBJECTIVE AND RATIONALE The objective herein was determine reproducible consistent findings regarding specific abundance, steroid hormone responsiveness, functionality, activation states, markers, systemically without endometriosis. SEARCH METHODS A comprehensive English language PubMed, Medline Google Scholar search conducted key terms that included endometriosis, inflammation, human eutopic/ectopic cells, population, system, macrophages, dendritic cells (DC), natural killer mast eosinophils, neutrophils, B T cells. OUTCOMES In endometriosis compared those some endometrial display similar cycle-phase variation, whereas macrophages (Mø), immature DC regulatory behave differently. pro-inflammatory Mø1 phenotype versus anti-inflammatory Mø2 predominates abnormal activity disease. Conflicting data largely derive from small studies, variably defined hormonal milieu different experimental approaches technologies. WIDER IMPLICATIONS Phenotyping subtypes essential niche homeostasis normally history can facilitate development innovative diagnostics therapeutics for symptoms compromised

Язык: Английский

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Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities

Nature Reviews Neurology, Год журнала: 2020, Номер 16(7), С. 381 - 400

Опубликована: Июнь 15, 2020

Pain medication plays an important role in the treatment of acute and chronic pain conditions, but some drugs, opioids particular, have been overprescribed or prescribed without adequate safeguards, leading to alarming rise medication-related overdose deaths. The NIH Helping End Addiction Long-term (HEAL) Initiative is a trans-agency effort provide scientific solutions stem opioid crisis. One component initiative support biomarker discovery rigorous validation collaboration with industry leaders accelerate high-quality clinical research into neurotherapeutics pain. use objective biomarkers trial end points throughout drug development process crucial help define pathophysiological subsets pain, evaluate target engagement new drugs predict analgesic efficacy drugs. In 2018, NIH-led Discovery Validation Biomarkers Develop Non-Addictive Therapeutics for workshop convened from academia, industry, government patient advocacy groups discuss progress, challenges, gaps ideas facilitate outcomes this are outlined Consensus Statement. strategies

Язык: Английский

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Etiology and Pharmacology of Neuropathic Pain

Pharmacological Reviews, Год журнала: 2018, Номер 70(2), С. 315 - 347

Опубликована: Март 2, 2018

Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, time-dependent processes, including neuroimmune interactions at peripheral, supraspinal, spinal levels, contribute etiology this "disease pain." Recent work emphasizes roles colony-stimulating factor 1, ATP, brain-derived neurotrophic factor. Excitatory processes are enhanced, inhibitory attenuated in dorsal horn throughout somatosensory system. This leads central sensitization aberrant processing such that tactile innocuous thermal information is perceived as pain (allodynia). Processes involved onset differ from those its long-term maintenance. Opioids display limited effectiveness, less than 35% patients derive meaningful benefit other therapeutic approaches. We thus review promising targets have emerged over last 20 years, Na⁺, K⁺, Ca²⁺, hyperpolarization-activated cyclic nucleotide–gated channels, transient receptor potential channel type V1 adenosine A3 receptors. Despite progress, gabapentinoids retain their status first-line treatments, yet mechanism action poorly understood. outline recent progress understanding show how has provided insights into cellular actions pregabalin gabapentin. Interactions with α2δ-1 subunit voltage-gated Ca²⁺ channels produce multiple neuron type-specific cord higher centers. suggest drugs affect rather a single specific target, greatest promise for future development.

Язык: Английский

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