Faculty Opinions recommendation of Treatment of central sensitization in patients with 'unexplained' chronic pain: an update.

2016 ◽  
Author(s):  
Massimo Allegri
Keyword(s):  
Chronic Pain ◽  
Central Sensitization

scholarly journals A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 278-279
Author(s):  
M Defaye ◽  
N Abdullah ◽  
M Iftinca ◽  
C Altier
Keyword(s):  
Chronic Pain ◽  
Central Sensitization ◽  
Microglial Activation ◽  
Visceral Pain ◽  
Purinergic Signaling ◽  
Designer Drugs ◽  
Visceral Afferents ◽  
Peripheral Sensitization ◽  
Specific Expression

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship

Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: an fMRI study

2021 ◽  
Vol 126 (3) ◽  
pp. 946-956
Author(s):  
Roland Staud ◽  
Jeff Boissoneault ◽  
Song Lai ◽  
Marlin S. Mejia ◽  
Riddhi Ramanlal ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neural Activity ◽  
Central Sensitization ◽  
Temporal Summation ◽  
Time Course ◽  
Pain Modulation ◽  
Healthy Controls ◽  
Fmri Study ◽  
Second Pain

“Windup” and its behavioral correlate “temporal-summation-of-second pain” (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.

Pain Pathways and Nervous System Plasticity: Learning and Memory in Pain

Pain Medicine ◽  
2019 ◽  
Vol 20 (12) ◽  
pp. 2421-2437 ◽  
Author(s):  
Bill McCarberg ◽  
John Peppin
Keyword(s):  
Chronic Pain ◽  
Neural Plasticity ◽  
Central Sensitization ◽  
Long Term Potentiation ◽  
Functional Changes ◽  
Pain Pathways ◽  
Term Potentiation ◽  
Pain Chronification ◽  
Longitudinal Imaging

Abstract Objective This article reviews the structural and functional changes in pain chronification and explores the association between memory and the development of chronic pain. Methods PubMed was searched using the terms “chronic pain,” “central sensitization,” “learning,” “memory,” “long-term potentiation,” “long-term depression,” and “pain memory.” Relevant findings were synthesized into a narrative of the processes affecting pain chronification. Results Pain pathways represent a complex sensory system with cognitive, emotional, and behavioral influences. Anatomically, the hippocampus, amygdala, and anterior cortex—central to the encoding and consolidation of memory—are also implicated in experiential aspects of pain. Common neurotransmitters and similar mechanisms of neural plasticity (eg, central sensitization, long-term potentiation) suggest a mechanistic overlap between chronic pain and memory. These anatomic and mechanistic correlates indicate that chronic pain and memory intimately interact on several levels. Longitudinal imaging studies suggest that spatiotemporal reorganization of brain activity accompanies the transition to chronic pain, during which the representation of pain gradually shifts from sensory to emotional and limbic structures. Conclusions The chronification of pain can be conceptualized as activity-induced plasticity of the limbic–cortical circuitry resulting in reorganization of the neocortex. The state of the limbic–cortical network determines whether nociceptive signals are transient or chronic by extinguishing pathways or amplifying signals that intensify the emotional component of nociceptive inputs. Thus, chronic pain can be seen as the persistence of the memory of pain and/or the inability to extinguish painful memories. Ideally, pharmacologic, physical, and/or psychological approaches should reverse the reorganization accompanying chronic pain.

scholarly journals Establishing Central Sensitization–Related Symptom Severity Subgroups: A Multicountry Study Using the Central Sensitization Inventory

Pain Medicine ◽  
2020 ◽  
Vol 21 (10) ◽  
pp. 2430-2440
Author(s):  
Antonio I Cuesta-Vargas ◽  
Randy Neblett ◽  
Jo Nijs ◽  
Alessandro Chiarotto ◽  
Jeroen Kregel ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Symptom Severity ◽  
Central Sensitization ◽  
Latent Profile Analysis ◽  
Optimal Number ◽  
Cluster Solution ◽  
Total N ◽  
Related Symptom ◽  
Patient Reported ◽  
Central Sensitization Inventory

Abstract Objectives The goal of this study was to identify central sensitization–related symptom severity subgroups in a large multicountry sample composed of patients with chronic pain and pain-free individuals using the Central Sensitization Inventory (CSI). Methods A large, pooled international (N = 8 countries) sample of chronic pain patients plus healthy subjects (total N = 2,620) was randomly divided into two subsamples for cross-validation purposes. First, a hierarchical cluster analysis (HCA) was performed using CSI item-level data as clustering variables (test sample; N = 1,312). Second, a latent profile analysis (LPA) was conducted to confirm the optimal number of CSI clusters (validation sample; N = 1,308). Finally, to promote implementation in real-world clinical practice, we built a free online Central Sensitization Inventory Symptom Severity Calculator. Results In both HCA (N = 1,219 valid cases) and LPA (N = 1,245 valid cases) analyses, a three-cluster and three-profile solution, respectively, emerged as the most statistically optimal and clinically meaningful. Clusters were labeled as follows: (i) Low Level of CS-Related Symptom Severity, (ii) Medium Level of CS-Related Symptom Severity, and (iii) High Level of CS-Related Symptom Severity. Conclusions Our results indicated that a three-cluster solution clearly captured the heterogeneity of the CSI data. The calculator might provide an efficient way of classifying subjects into the cluster groups. Future studies should analyze the extent to which the CSI cluster classification correlates with other patient-reported and objective signs and symptoms of CS in patients with chronic pain, their associations with clinical outcomes, health-related costs, biomarkers, (etc.), and responsiveness to treatment.

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