Central Sensitization in the Bladder Pain Syndrome

Introduction: Nociceptive hyper-excitability and Central Sensitization (CS), have been identified as responsible for maintaining pain in several chronic neuropathic pain conditions, among which Bladder pain syndrome (BPS). Aim of the present study was to evaluate in patients with BPS the correlation between CS and the following items pain duration, the number of other CS related diseases, the number of tried treatments for pain and of diagnostic investigations before the proper diagnosis and to identify the cut-off value of the pain delays for predicting the worsening of sensitization. Method: Fifty-eight consecutively BPS outpatients were recruited from 2014 to 2016. They were submitted to Central Sensitization Inventory (CSI), Overactive Bladder Questionnaire (OAB-8v) and visual analogic scale (VAS) for pain. We used a descriptive analysis (mean, standard deviation, range) and Spearman and Kendall test coefficient as correlation index. One-way ANOVA test was used for the comparison between groups. P-value less than 0.05 were required for statistical significance. We used receiver operating characteristic (ROC) curve analysis to retrospectively analyze the association between the years of the disease and pathological values o of CSI. Results: The patients were observed after 13.1 + 11.0 years by the onset of The CSI score was 69.7+15.8. Resulting significantly lower in patients with BPS onset in the last year the correlation between CSI and the disease duration was significant. The number of previous investigations was 3.7 + 2.8while the number of previous treatments for chronic pain was 5.9 + 3.1, resulting significantly related to CSI score. The OAB-8v was 21 + 7.5 (range 2-34). The worsening of the symptoms related to the overactive bladder at OAB-8v was related to a greater CS. After 1,5 years of the onset of the pain the CS show a progressive worsening. The mean number of other diseases (fibromyalgia, irritable bowel syndrome, anxiety or depression, migraine, neck injury, Panic Disorder Attack, chronic fatigue syndrome, temporomandibular joint syndrome, restless leg syndrome, multiple chemical sensitivities) associated to CS was 2.8+1.9. The correlation between the number of diseases associated to CS and the years of disease resulted significant. Conclusion: Patients with long lasting pelvic pain show high levels of CS, and other central sensitivity syndromes (CSS) together to worsening of overactive bladder symptoms, and increasing number of used drugs. The delay of diagnosis is related to a greater sensitization process

Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain

Background: The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists. Objectives: Designing the first set of classification criteria for the classification of central sensitization pain. Methods: A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain. Results: It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory). Limitations: Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies. Conclusion: Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain

Patients with chronic spinal pain benefit from pain neuroscience education regardless the self-reported signs of central sensitization : secondary analysis of a randomized controlled multicenter trial

Background: Pain neuroscience education is effective in chronic pain management. Central sensitization (ie, generalized hypersensitivity) is often explained as the underlying mechanism for chronic pain, because of its clinical relevance and influence on pain severity, prognosis, and treatment outcome. Objectives: To examine whether patients with more or fewer symptoms of central sensitization respond differently to pain neuroscience education. Design: A secondary analysis of a multicenter, triple-blind randomized controlled trial. Setting: University Hospital Ghent and University Hospital Brussels, Belgium. Patients: 120 persons with chronic spinal pain with high or low self-reported symptoms of central sensitization. Interventions: Pain neuroscience education or neck/back school. Both interventions were delivered in 3 sessions: 1 group session, 1 online session, and 1 individual session. Main Outcome Measures: disability (primary), pain catastrophizing, kinesiophobia, illness perceptions, and hypervigilance. Results: Pain disability did not change in any group (P = .242). Regarding secondary outcomes: significant interaction effects were found for pain catastrophizing (P-values: P = .02 to P = .05), kinesiophobia (P = .02), and several aspects of illness perceptions (chronicity: P = .002; negative consequences: P = .02; personal control: P = .02; and cyclicity: P = .02). Bonferroni post hoc analysis showed that only the pain neuroscience education group (high and low self-reported symptoms of central sensitization) showed a significant improvement regarding kinesiophobia (P < .001, medium effect sizes), perceived negative consequence (P = .004 and P < .001, small to medium effect sizes), and perceived cyclicity of the illness (P = .01 and P = .01, small effect sizes). Pain catastrophizing only significantly reduced in people with high self-reported central sensitization symptoms (P < .05). Conclusion: Pain neuroscience education is useful in all patients with chronic spinal pain as it improves kinesiophobia and the perceived negative consequences and cyclicity of the illness regardless the self-reported signs of central sensitization. Regarding pain catastrophizing, pain neuroscience education is more effective in patients with high self-reported symptoms of central sensitization

The effect of gabapentin and pregabalin on symptoms other than pain and seizures. A review of the evidence

Gabapentin and pregabalin are drugs that act through reduction of the central sensitization. They are useful in conditions such as partial seizures and neuropathic pain. However, in the last decade these drugs appear to have been effective against a variety of other symptoms, such as pruritus, hot flushes in post-menopausal women and intractable hiccups. The drugs are probably also effective for many other symptoms related to central sensitization but the paucity of data does not allow for support of these claims. Both gabapentin and pregabalin have a good safety record.Gabapentin and pregabalin are drugs that act through reduction of the central sensitization. They are useful in conditions such as partial seizures and neuropathic pain. However, in the last decade these drugs appear to have been effective against a variety of other symptoms, such as pruritus, hot flushes in post-menopausal women and intractable hiccups. The drugs are probably also effective for many other symptoms related to central sensitization but the paucity of data does not allow for support of these claims. Both gabapentin and pregabalin have a good safety record

The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin

Protein kinases and phosphatases catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial signaling proteins in central nervous system. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. To explore the role of protein phosphatase in central sensitization of spinal nociceptive neurons following peripheral noxious stimulation, using electrophysiological recording techniques, we investigated the role of two inhibitors of protein phosphatase type 2A (PP2A), fostriecin and okadaic acid (OA), on the responses of dorsal horn neurons to mechanical stimuli in anesthetized rats following intradermal injection of capsaicin. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. A microdialysis fiber was implanted in the spinal cord dorsal horn for perfusion of ACSF and inhibitors of PP2A, fostriecin and okadaic acid. We found that in ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased over a period of 15 min after injection and had mostly recovered by 60 min later. However, pre- or post-treatment with the phosphatase inhibitors, fostriecin or OA, significantly enhanced the effects of capsaicin injection by prolonging the responses to more than 3 hours. These results confirm that blockade of protein phosphatase activity may potentiate central sensitization of nociceptive transmission in the spinal cord following capsaicin injection and indicate that protein phosphatase type 2A may be involved in determining the duration of capsaicin-induced central sensitization

Ketamine as an adjuvant in sympathetic blocks for management of central sensitization following peripheral nerve injury

Proliferation of NMDA receptors and role of glutamate in producing central sensitization and 'wind up' phenomena in CRPS [complex regional pain syndrome] forms a strong basis for the use of Ketamine to block the cellular mechanisms that initiate and maintain these changes. In this case series, we describe 3 patients of CRPS Type II with debilitating central sensitization, heat/mechano allodynia and cognitive symptoms that we termed 'vicarious pain'. Each of these patients had dramatic relief with addition of Ketamine as an adjuvant to the sympathetic blocks after conventional therapy failed

A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia

Repeated exposure to pain can result in sensitization of the central nervous system, enhancing subsequent pain and potentially leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit, but the degree that this can be accomplished volitionally remains unknown. Here we investigated whether a brief (~5 min) cognitive-behavioural intervention could modify pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). In each of 8 sessions, 2 groups of healthy human subjects received a series of painful thermal stimuli that resulted in secondary hyperalgesia. One group (regulate) was given brief pain-focused cognitive training at each session, while the other group (control) received a non-pain-focused intervention. The intervention selectively reduced pain unpleasantness but not pain intensity in the regulate group. Furthermore, secondary hyperalgesia was significantly reduced in the regulate group compared with the control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts

The Relationship Between Pain Sensitivity And Motor Adaptations

The perception of pain in patient populations can arise from tissue damage but when pain persists past the point of tissue healing it is thought to relate to abnormal pain processing in the CNS such as persistent central sensitization. Studies have shown that persistent central sensitization occurs in about 1/3 of people with chronic pain from knee OA and this abnormal pain processing can affect motor output and motor adaptation. It is unclear whether individuals with OA and persistent sensitization are predisposed to heightened pain perception or whether they develop heightened pain as a result of the chronic pain from OA. The purpose of this study is to determine the influence of heightened pain sensitivity on motor output and motor adaptation. We designed this study to determine the relationships between central sensitization (temporal summation and conditioned pain modulation) and motor output and adaptations that are measured by the “broken escalator phenomenon”. This poster outlines the preliminary work associated with the design of this study.https://dune.une.edu/pt_studrrposter/1001/thumbnail.jp