Visceral Pain: Mechanisms of Peripheral and Central Sensitization

1995 ◽  
Vol 27 (2) ◽  
pp. 235-239 ◽  
Author(s):  
Fernando Cervero
Keyword(s):  
Central Sensitization ◽  
Visceral Pain ◽  
Pain Mechanisms

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

Central sensitization in chronic lumbar spine pain – possibilities of therapeutic interventions

Ból ◽  
2020 ◽  
Vol 21 (2) ◽  
pp. 45-53
Author(s):  
Barbara Kosińska ◽  
Paweł Turczyn ◽  
Krzysztof Wesołowski ◽  
Beata Tarnacka ◽  
Małgorzata Malec-Milewska
Keyword(s):  
Low Back Pain ◽  
Central Sensitization ◽  
Diagnostic Tests ◽  
Multimodal Therapy ◽  
Underlying Mechanism ◽  
Therapeutic Interventions ◽  
Low Back ◽  
Pain Mechanisms ◽  
Factors Affecting ◽  
Spine Pain

Patients with chronic low back pain are a heterogeneous group. Therapeutic management of these patients should address the underlying mechanism of pain, which can be revealed after performing diagnostic tests. The management of patients with the predominant central sensitization component of includes multimodal therapy consisting of pharmacological and non-pharmacological treatment. An important element is also the identification and exclusion of the most important pathophysiological factors affecting the maintenance of central sensitization mechanisms in each patient. The paper describes pharmacological and non-pharmacological therapeutic options in patients with central sensitization component, considering that these methods may differ significantly in the patients. It should be stated that despite the individualized, multimodal therapy based on pain mechanisms, in some patients substantial pain relief may not be achieved.

(123) Visceral Pain Mechanisms: Features of Constant Pain and Genetic Linkage in Chronic Pancreatitis Patients

2019 ◽  
Vol 20 (4) ◽  
pp. S7
Author(s):  
D. Whitcomb ◽  
J. Saloman ◽  
A. Phillips ◽  
P. Greer ◽  
C. Shelton ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Genetic Linkage ◽  
Visceral Pain ◽  
Pain Mechanisms ◽  
Constant Pain

The sensory and affective components of pain

1997 ◽  
Vol 20 (3) ◽  
pp. 439-440 ◽  
Author(s):  
Fabrizio Benedetti
Keyword(s):  
Sex Differences ◽  
Visceral Pain ◽  
Therapeutic Strategies ◽  
Pain Mechanisms ◽  
Pain Experience ◽  
Affective Component ◽  
Psychological Mechanisms ◽  
Affective Pain ◽  
Affective Components ◽  
Global Pain

Both the sensory and the motivational-affective component of pain must be taken into account in studies on sex differences as well as on neuropathic, postoperative, sympathetic, and visceral pain. In all these cases, therapeutic strategies should be aimed at controlling the peripheral, central, and psychological mechanisms underlying the global pain experience. Similarly, it should be recalled that some neuropeptides act on both sensory and affective pain mechanisms. [berkley; mcmahon; dickenson; coderre & katz; wiesenfeld-hallin et al.; blumberg et al.]

scholarly journals Toward an effective peripheral visceral analgesic: responding to the national opioid crisis

2018 ◽  
Vol 314 (6) ◽  
pp. G637-G646 ◽  
Author(s):  
Michael Camilleri
Keyword(s):  
Abdominal Pain ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Visceral Pain ◽  
Receptor Potential ◽  
Opioid Peptide ◽  
Current Evidence ◽  
Orphanin Fq ◽  
Pain Mechanisms ◽  
Opioid Crisis

This mini-review summarizes recent new developments in visceral analgesics. This promising field is important, as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors via biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor, or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds target nonopioid mechanisms, including cannabinoid (CB2), N-methyl-d-aspartate, calcitonin gene-related peptide, estrogen, and adenosine A2B receptors and transient receptor potential (TRP) channels (TRPV1, TRPV4, and TRPM8). Although current evidence is based predominantly on animal models of visceral pain, early human studies also support the evidence from the basic and animal research. This augurs well for the development of nonaddictive, visceral analgesics for treatment of chronic abdominal pain, an unmet clinical need.

scholarly journals Central neural mechanisms mediating human visceral hypersensitivity

2001 ◽  
Vol 281 (5) ◽  
pp. G1196-G1202 ◽  
Author(s):  
Sanchoy Sarkar ◽  
Anthony R. Hobson ◽  
Paul L. Furlong ◽  
Clifford J. Woolf ◽  
David G. Thompson ◽  
...  
Keyword(s):  
Central Sensitization ◽  
Pain Threshold ◽  
Visceral Pain ◽  
Functional Gastrointestinal Disorders ◽  
Neural Mechanisms ◽  
Visceral Hypersensitivity ◽  
Afferent Pathway ◽  
Healthy Human ◽  
Pain Pathway ◽  
Stimulation Of

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 ± 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 ± 2.3 and 15.8 ± 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.

Neuroimaging of the human visceral pain system–A methodological review

2011 ◽  
Vol 2 (3) ◽  
pp. 95-104 ◽  
Author(s):  
Jens Brøndum Frøkjær ◽  
Søren Schou Olesen ◽  
Carina Graversen ◽  
Trine Andresen ◽  
Dina Lelic ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Temporal Resolution ◽  
High Spatial Resolution ◽  
Visceral Pain ◽  
Imaging Techniques ◽  
Brain Activity ◽  
Pharmacological Intervention ◽  
Pain Processing ◽  
Pain Mechanisms ◽  
The Brain

AbstractDuring the last decades there has been a tremendous development of non-invasive methods for assessment of brain activity following visceral pain. Improved methods for neurophysiological and brain imaging techniques have vastly increased our understanding of the central processing of gastrointestinal sensation and pain in both healthy volunteers as well as in patients suffering from gastrointestinal disorders. The techniques used are functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG)/evoked brain potentials (EPs), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), and the multimodal combinations of these techniques. The use of these techniques has brought new insight into the complex brain processes underlying pain perception, including a number of subcortical and cortical regions, and paved new ways in our understanding of acute and chronic pain. The pathways are dynamic with a delicate balance between facilitatory and inhibitory pain mechanisms, and with modulation of the response to internal or external stressors with a high degree of plasticity. Hence, the ultimate goal in imaging of pain is to follow the stimulus response throughout the neuraxis.Brain activity measured by fMRI is based on subtracting regional changes in blood oxygenation during a resting condition from the signal during a stimulus condition, and has high spatial resolution but low temporal resolution. SPECT and PET are nuclear imaging techniques where radiolabeled molecules are injected with visualization of the distribution, density and activity of receptors in the brain allowing not only assessment of brain activity but also study of receptor sites. EEG is based on assessment of electrical activity in the brain, and recordings of the resting EEG and evoked potentials following an external stimulus are used to study normal visceral pain processing, alterations of pain processing in different patient groups and the effect of pharmacological intervention. EEG has high temporal resolution, but relative poor spatial resolution, which however to some extent can be overcome by applying inverse modelling algorithms and signal decomposition procedures. MEG is based on recording the magnetic fields produced by electrical currents in the brain, has high spatial resolution and is especially suitable for the study cortical activation.The treatment of chronic abdominal pain is often ineffective and dissapointing, which leads to search for optimized treatment achieved on the basis of a better understanding of underlying pain mechanisms. Application of the recent improvements in neuroimaging on the visceral pain system may likely in near future contribute substantially to our understanding of the functional and structural pathophysiology underlying chronic visceral pain disorders, and pave the road for optimized individual and mechanism based treatments.The purpose of this review is to give a state-of-the-art overview of these methods, with focus on EEG, and especially the advantages and limitations of the single methods in clinical gastrointestinal pain esearch including examples from relevant studies.

scholarly journals Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Onosi S. Ifesemen ◽  
Daniel F. McWilliams ◽  
Eamonn Ferguson ◽  
Richard Wakefield ◽  
Kehinde Akin-Akinyosoye ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Outcome Measures ◽  
Central Sensitization ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Text Messages ◽  
Self Report ◽  
Pain Mechanisms ◽  
Link Type ◽  
Patient Reported

Abstract Background Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA. Methods/design This is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated. Discussion This study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation. Trial registration Clinicaltrials.gov NCT04515589. Date of registration 17 August 2020.

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