Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management

Brain, Journal Year: 2021, Volume and Issue: 144(6), P. 1632 - 1645

Published: March 9, 2021

Peripheral neuropathy is one of the most common complications both type 1 and 2 diabetes. Up to half patients with diabetes develop during course their disease, which accompanied by neuropathic pain in 30-40% cases. nerve injury can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, mononeuropathies. The diabetic we will refer DN, its characteristic glove stocking like presentation sensory or motor function loss. DN painful counterpart, are associated increased mortality morbidity; thus, early recognition preventive measures essential. Nevertheless, it not easy diagnose particularly mild there currently no single established diagnostic gold standard. approach research a hierarchical system, combines symptoms, signs, series confirmatory tests. general lack long-term prospective studies has limited evaluation sensitivity specificity new morphometric neurophysiological techniques. Thus, best paradigm for screening clinical practice remains uncertain. Herein, review challenges from perspectives implications managing DN. There treatment, apart improved glycaemic control, more effective than diabetes, only symptomatic management available Currently, less one-third derive sufficient relief existing pharmacotherapies. A precise distinct profile may help identify responsive treatment versus another. Detailed profiles lead tailored patient subgroups matching novel pathomechanisms also trials stratification. Large randomized needed interventions, i.e. pharmacological, physical, cognitive, educational, etc., therapeutic outcomes.

Language: Английский

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Neocortical circuits in pain and pain relief

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(8), P. 458 - 471

Published: June 14, 2021

Language: Английский

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How does hip osteoarthritis differ from knee osteoarthritis?

Osteoarthritis and Cartilage, Journal Year: 2021, Volume and Issue: 30(1), P. 32 - 41

Published: Sept. 29, 2021

Language: Английский

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Pain-resolving immune mechanisms in neuropathic pain

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: unknown

Published: March 1, 2023

Language: Английский

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Neuropathic pain caused by miswiring and abnormal end organ targeting

Nature, Journal Year: 2022, Volume and Issue: 606(7912), P. 137 - 145

Published: May 25, 2022

Abstract Nerve injury leads to chronic pain and exaggerated sensitivity gentle touch (allodynia) as well a loss of sensation in the areas which injured non-injured nerves come together 1–3 . The mechanisms that disambiguate these mixed paradoxical symptoms are unknown. Here we longitudinally non-invasively imaged genetically labelled populations fibres sense noxious stimuli (nociceptors) (low-threshold afferents) peripherally skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour same mice. Fully denervated initially lost sensation, gradually recovered normal developed marked allodynia aversion several injury. This reinnervation-induced neuropathic involved nociceptors sprouted into territories precisely reproducing initial pattern innervation, were guided by blood vessels showed irregular terminal connectivity lowered activation thresholds mimicking low-threshold afferents. By contrast, afferents—which normally mediate intact 4–7 —did not reinnervate, leading an aberrant innervation tactile end organs such Meissner corpuscles with alone. Genetic ablation fully abrogated reinnervation allodynia. Our results thus reveal emergence form is driven structural plasticity, abnormal malfunction during reinnervation, provide mechanistic framework sensory manifestations observed clinically can impose heavy burden on patients.

Language: Английский

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Antidepressants for pain management in adults with chronic pain: a network meta-analysis

Cochrane library, Journal Year: 2023, Volume and Issue: 2023(5)

Published: May 10, 2023

Language: Английский

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Microglia polarization in nociplastic pain: mechanisms and perspectives

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(3), P. 1053 - 1067

Published: April 17, 2023

Abstract Nociplastic pain is the third classification of as described by International Association for Study Pain (IASP), in addition to neuropathic and nociceptive classes. The main pathophysiological mechanism developing nociplastic central sensitization (CS) which amplification hypersensitivity occur. Fibromyalgia prototypical disorder, characterized allodynia hyperalgesia. Much scientific data suggest that classical activation microglia spinal cord mediates neuroinflammation plays an essential role CS. In this review article, we discuss impact M1/M2 polarization on pain, besides molecular mechanisms engaged process. addition, mention microglial modulators offers a novel therapeutic alternative management disorders. Graphical abstract Illustrating underlying pain. LPS lipopolysaccharide, TNF-α tumor necrosis factor-α, INF-γ Interferon gamma, ATP adenosine triphosphate, 49 P2Y12/13R purinergic P2Y 12/13 receptor, P2X4/7R P2X 4/7 SP Substance P, NK-1R Neurokinin 1 CCL2 CC motif ligand 2, CCR2 2 CSF-1 colony-stimulating factor 1, CSF-1R CX3CL1 CX3C CX3XR1 TLR toll-like MAPK mitogen-activated protein kinases, JNK jun N-terminal kinase, ERK extracellular signal-regulated iNOS Inducible nitric oxide synthase, IL-1β interleukin-1β, IL-6 interleukin-6, BDNF brain-derived neurotrophic factor, GABA γ-Aminobutyric acid, GABAR acid NMDAR N-methyl-D-aspartate AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropi-onic IL-4 interleukin-4, IL-13 interleukin-13, IL-10 interleukin-10, Arg-1 Arginase FGF fibroblast growth GDNF glial cell-derived IGF-1 insulin-like factor-1, NGF nerve CD Cluster differentiation.

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Advances and challenges in neuropathic pain: a narrative review and future directions

British Journal of Anaesthesia, Journal Year: 2023, Volume and Issue: 131(1), P. 79 - 92

Published: May 18, 2023

Language: Английский

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Antidepressants for pain management in adults with chronic pain: a network meta-analysis

Health Technology Assessment, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 155

Published: Oct. 1, 2024

Background Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across chronic conditions, so effectiveness safety for most conditions remain unknown. Objective To assess the efficacy of (except headache) in adults. Our primary outcomes were as follows: substantial relief (50%), intensity, mood adverse events. secondary moderate (30%), physical function, sleep, quality life, Patient Global Impression Change, serious events withdrawal. Design This was systematic review with meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED PsycINFO databases randomised controlled trials up until 4 January 2022. The registered PROSPERO (CRD42020171855), protocol published Cochrane Library (https://doi.org/10.1002/14651858.CD014682). Setting analysed from settings. Participants included which participants had pain, defined longer than 3 months, any condition excluding headache. Interventions antidepressants. Main outcome measures relief, reduction ˃ 50%. also measured Secondary (above 30% reduction), events, withdrawal trial. Results identified 176 studies total 28,664 participants. Most placebo-controlled ( n = 83) parallel armed 141). examined fibromyalgia (59 studies), neuropathic (49 studies) musculoskeletal (40 studies). average length 10 weeks. short-term only excluded people low other mental health conditions. Across outcomes, duloxetine consistently highest-ranked antidepressant moderate- high-certainty evidence. Standard dose equally efficacious high majority outcomes. Milnacipran often ranked next antidepressant, although certainty evidence lower that duloxetine. There insufficient draw robust conclusions Limitations poor. For duloxetine, it clear whether effect applies groups both mood, since these trials. on long-term effects. Conclusions reliable treatment Duloxetine moderately at standard dose. promising milnacipran, further high-quality research needed be confident conclusions. Data certainty. findings should read an encouragement prescribe where non-pharmacological intervention could effective, especially absence good side effects safety. Future work need large, methodologically sound testing These examine (> 6 months) include mood. better reporting tolerance drugs, compliance. Study registration study CRD42020171855. Funding award funded by National Institute Health Care Research (NIHR) Technology Assessment programme (NIHR ref: NIHR128782) full ; Vol. 28, No. 62. See NIHR Awards website information.

Language: Английский

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