The method simulating spontaneous pain in patients with nociplastic pain using rats with fibromyalgia-like condition.
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ABSTRACT:
SUBMITTER: Tanei S
PROVIDER: S-EPMC7078388 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveNociplastic concept incorporates a broad continuum of pain phenotypes shared with clinical peculiarity. This study aimed to develop and validate a diagnostic tool, the preliminary Nociplastic-based Fibromyalgia Features (NFF), to detect fibromyalgia (FM) in patients with chronic pain.MethodsItems requiring yes or no responses and relating to the most relevant clinical nociplastic pain (NP) features of FM were compiled by a group of expert rheumatologists. The provisional list was tested in a prospective study on 185 consecutive patients with chronic pain (126 patients with FM and 59 patients with non-FM non-inflammatory chronic pain) diagnosed based on expert decision. Identification of the most discriminant combinations of items for FM and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. All participants were investigated through the final NFF, the 2011 American College of Rheumatology (ACR) criteria, and the 2016 ACR criteria. NFF performance was assessed with receiver operating characteristic curve analysis.ResultsBased on multivariate analyses, we retained only seven items in the final version of the NFF. A cut-off score of 4 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (85%), with a sensitivity of 82% and a specificity of 91%. The NFF showed the highest concordance rate with expert diagnosis (85%) and the lowest value (77%) with the ACR 2016 criteria.ConclusionThe preliminary NFF with respect to the various aspects of NP showed good performance for detection of the FM in the clinical setting. This tool may provide a more pragmatic approach to the timely diagnosis of FM.
| S-EPMC8916565 | biostudies-literature
Project description:Fibromyalgia (FM) is a chronic pain condition and consists of widespread pain with similarities to neuropathic pain in clinical findings, pathophysiology, and neuropharmacology. Its mechanisms are poorly understood and a lack of effective biomarkers for diagnosis and onset prediction. This study aimed to identify the metabolites to characterize pain and sngception (Sng) in FM.
2022-08-12 | PXD022886 | Pride
Project description:Nociplastic pain is the third classification of pain as described by the International Association for the Study of Pain (IASP), in addition to the neuropathic and nociceptive pain classes. The main pathophysiological mechanism for developing nociplastic pain is central sensitization (CS) in which pain amplification and hypersensitivity occur. Fibromyalgia is the prototypical nociplastic pain disorder, characterized by allodynia and hyperalgesia. Much scientific data suggest that classical activation of microglia in the spinal cord mediates neuroinflammation which plays an essential role in developing CS. In this review article, we discuss the impact of microglia activation and M1/M2 polarization on developing neuroinflammation and nociplastic pain, besides the molecular mechanisms engaged in this process. In addition, we mention the impact of microglial modulators on M1/M2 microglial polarization that offers a novel therapeutic alternative for the management of nociplastic pain disorders. Illustrating the mechanisms underlying microglia activation in central sensitization and nociplastic 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 purinergic P2X 4/7 receptor, SP Substance P, NK-1R Neurokinin 1 receptor, CCL2 CC motif ligand 2, CCR2 CC motif ligand 2 receptor, CSF-1 colony-stimulating factor 1, CSF-1R colony-stimulating factor 1 receptor, CX3CL1 CX3C motif ligand 1, CX3XR1 CX3C motif ligand 1 receptor, TLR toll-like receptor, MAPK mitogen-activated protein kinases, JNK jun N-terminal kinase, ERK extracellular signal-regulated kinase, iNOS Inducible nitric oxide synthase, IL-1β interleukin-1β, IL-6 interleukin-6, BDNF brain-derived neurotrophic factor, GABA γ-Aminobutyric acid, GABAR γ-Aminobutyric acid receptor, NMDAR N-methyl-D-aspartate receptor, AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropi-onic acid receptor, IL-4 interleukin-4, IL-13 interleukin-13, IL-10 interleukin-10, Arg-1 Arginase 1, FGF fibroblast growth factor, GDNF glial cell-derived neurotrophic factor, IGF-1 insulin-like growth factor-1, NGF nerve growth factor, CD Cluster of differentiation.
| S-EPMC10229465 | biostudies-literature
Project description:Fibromyalgia is a chronic pain syndrome characterized by widespread pain. The pathophysiology of fibromyalgia is not clearly understood and there are no specific biomarkers available for accurate diagnosis. Here we define genomic signatures using high throughput RNA sequencing on 96 fibromyalgia and 93 matched controls. Our findings revealed two major fibromyalgia-associated expression signatures. The first group included 44 patients with a signature enriched for gene expression associated with extracellular matrix and downregulation of RhoGDI signaling pathway. The second group included 31 patients and showed a profound reduction in the expression of inflammatory mediators with an increased expression of genes involved in the CLEAR signaling pathway. These results suggest defective tissue homeostasis associated with the extra-cellular matrix and cellular program that regulates lysosomal biogenesis and participates in macromolecule clearance in fibromyalgia. Further elucidation of these pathways will lead to development of accurate diagnostic markers, and effective therapeutic options for fibromyalgia.
2024-02-21 | GSE221921 | GEO
Project description:Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5-6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.
| S-EPMC9189106 | biostudies-literature
Project description:Exploring the relationship between nociplastic pain and the severity and impact of pelvic pain symptoms could lend insight into the heterogeneous symptom presentation and treatment response that complicates management of chronic pelvic pain. In this prospective cross-sectional study, we sought to evaluate relationships between degree of nociplastic pain, measured by the Fibromyalgia (FM) Survey Score, and multiple aspects of the chronic pelvic pain (CPP) experience, including severity, frequency, tenderness during pelvic myofascial exam, interference with daily life, and high-impact pain. The study included 303 women who presented to a tertiary referral clinic for chronic pelvic pain and endometriosis. Multiple measures of pelvic pain, including pain severity, frequency, interference, pelvic myofascial pain, and high-impact pain were examined in General Linear Models with FM Survey Score as the primary predictor of interest in models controlling for endometriosis, surgical history, use of opioids, body mass index, and patient age. Higher level of nociplastic pain was associated with greater pelvic pain severity, frequency, interference, and pelvic myofascial pain (all P < .05). For all models, degree of nociplastic pain was more strongly associated with pain outcomes than the presence of endometriosis, and use of opioids was the only stronger predictor of worse pain outcomes. The likelihood of high impact pain increased 7% for each additional point on the FM Survey Score. Degree of nociplastic pain was robustly associated with severity, frequency, and impact of pelvic pain, and was independent of the presence of endometriosis, history of surgical procedures for pelvic pain, age, and BMI. Trial registration: not applicable PERSPECTIVE: This article evaluates the impact of nociplastic pain on symptoms and functional status in chronic pelvic pain. These findings raise the possibility that a simple screening tool for nociplastic pain might provide clinically actionable information without the need for deep neurobiological phenotyping and may inform development of personalized management strategies.
| S-EPMC10511662 | biostudies-literature
Project description:AbstractAcute injury-induced pain can transition to chronic nociplastic pain, which predominantly affects women. To facilitate studies on the underlying mechanisms of nociplastic pain, we developed a mouse model in which postinjury thermal stimulation (intermittent 40°C water immersion for 10 minutes at 2 hours postcapsaicin) prolongs capsaicin (ie, experimental injury)-induced transient mechanical hypersensitivity outside of the injury area. Although capsaicin injection alone induced mechanical and thermal hypersensitivity that resolved in ∼7 days (slower recovery in females), the postinjury stimulation prolonged capsaicin-induced mechanical, but not thermal, hypersensitivity up to 3 weeks in both sexes. When postinjury stimulation was given at a lower intensity (30°C) or at later time points (40°C at 1-3 days postcapsaicin), chronification of mechanical hypersensitivity occurred only in females. Similar chronification could be induced by a different postinjury stimulation modality (vibration of paw) or with a different injury model (plantar incision). Notably, the 40°C postinjury stimulation did not prolong capsaicin-induced inflammation in the hind paw, indicating that the prolonged mechanical hypersensitivity in these mice arises without clear evidence of ongoing injury, reflecting nociplastic pain. Although morphine and gabapentin effectively alleviated this persistent mechanical hypersensitivity in both sexes, sexually dimorphic mechanisms mediated the hypersensitivity. Specifically, ongoing afferent activity at the previously capsaicin-injected area was critical in females, whereas activated spinal microglia were crucial in males. These results demonstrate that postinjury stimulation of the injured area can trigger the transition from transient pain to nociplastic pain more readily in females, and sex-dependent mechanisms maintain the nociplastic pain state.
| S-EPMC8669020 | biostudies-literature
Project description:Spontaneous hemodynamic signals fluctuate coherently within many resting-brain functional networks not only in awake humans and lightly anesthetized primates but also in animals under deep anesthesia characterized by burst-suppression electroencephalogram (EEG) activity and unconsciousness. To understand the neural origin of spontaneous hemodynamic fluctuations under such a deep anesthesia state, epidural EEG and cerebral blood flow (CBF) were simultaneously recorded from the bilateral somatosensory cortical regions of rats with isoflurane-induced burst-suppression EEG activity. Strong neurovascular coupling was observed between spontaneous EEG "bursts" and CBF "bumps," both of which were also highly synchronized across the 2 hemispheres. Functional magnetic resonance imaging (fMRI) was used to image spontaneous blood oxygen level-dependent (BOLD) signals under the same anesthesia conditions and showed similar BOLD "bumps" and dependence on anesthesia depth as the CBF signals. The spatiotemporal BOLD correlations indicate a strong but less-specific coherent network covering a wide range of cortical regions. The overall findings reveal that the spontaneous CBF/BOLD fluctuations under unconscious burst-suppression anesthesia conditions originate mainly from underlying neural activity. They provide insights into the neurophysiological basis for the use of BOLD- and CBF-based fMRI signals for noninvasively imaging spontaneous and synchronous brain activity under various brain states.
| S-EPMC3020581 | biostudies-literature
Project description:The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings.
| S-EPMC9982683 | biostudies-literature
Project description:Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1-S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.
| S-EPMC9562711 | biostudies-literature