scholarly journals An Exploratory Study of Endogenous Pain Modulatory Function in Patients Following Mild Traumatic Brain Injury

Pain Medicine ◽  
2019 ◽  
Vol 20 (11) ◽  
pp. 2198-2207 ◽  
Author(s):  
Christopher Carey ◽  
Jonathan Saxe ◽  
Fletcher A White ◽  
Kelly M Naugle
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Exploratory Study ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Thresholds ◽  
Pressure Pain Thresholds ◽  
Post Traumatic ◽  
Headache Pain ◽  
Pain Inhibition

AbstractBackground. Recent animal research suggests that mild traumatic brain injury (mTBI) facilitates abnormal endogenous modulation of pain, potentially underlying the increased risk for persistent headaches following injury. However, no human studies have directly assessed the functioning of endogenous facilitory and inhibitory systems in the early stages after an mTBI. Objective. The purpose of this exploratory study was to examine trigeminal sensitization and endogenous pain inhibitory capacity in mTBI patients in the acute stage of injury compared with matched controls. We also examined whether post-traumatic headache pain intensity within the mTBI sample was related to sensitization and pain inhibitory capacity. Methods. Twenty-four mTBI patients recruited from emergency departments and 21 age-, race-, and sex-matched controls completed one experimental session. During this session, participants completed quantitative sensory tests measuring trigeminal sensitization (pressure pain thresholds and temporal summation of pain in the head) and endogenous pain inhibition (conditioned pain modulation). Participants also completed validated questionnaires measuring headache pain, depression, anxiety, and pain catastrophizing. Results. The results revealed that the mTBI group exhibited significantly decreased pressure pain thresholds of the head and decreased pain inhibition on the conditioned pain modulation test compared with the control group. Furthermore, correlational analysis showed that the measures of trigeminal sensitization and depression were significantly associated with headache pain intensity within the mTBI group. Conclusions. In conclusion, mTBI patients may be at risk for maladaptive changes to the functioning of endogenous pain modulatory systems following head injury that could increase risk for post-traumatic headaches.

scholarly journals The role of deficient pain modulatory systems in the development of persistent post-traumatic headaches following mild traumatic brain injury: an exploratory longitudinal study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kelly M. Naugle ◽  
Christopher Carey ◽  
Eric Evans ◽  
Jonathan Saxe ◽  
Ryan Overman ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Pain Catastrophizing ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Mild Tbi ◽  
Inhibitory Capacity ◽  
Pressure Pain Thresholds ◽  
Post Traumatic

Abstract Background Post-traumatic headache (PTH) is one of the most common and long-lasting symptoms following mild traumatic brain injury (TBI). However, the pathological mechanisms underlying the development of persistent PTH remain poorly understood. The primary purpose of this prospective pilot study was to evaluate whether early pain modulatory profiles (sensitization and endogenous pain inhibitory capacity) and psychological factors after mild TBI predict the development of persistent PTH in mild TBI patients. Methods Adult mild TBI patients recruited from Level I Emergency Department Trauma Centers completed study sessions at 1–2 weeks, 1-month, and 4-months post mild TBI. Participants completed the following outcome measures during each session: conditioned pain modulation to measure endogenous pain inhibitory capacity, temporal summation of pain and pressure pain thresholds of the head to measure sensitization of the head, Pain Catastrophizing Scale, Center for Epidemiological Studies – Depression Scale, and a standardized headache survey. Participants were classified into persistent PTH (PPTH) and no-PPTH groups based on the 4-month data. Results The results revealed that mild TBI patients developing persistent PTH exhibited significantly diminished pain inhibitory capacity, and greater depression and pain catastrophizing following injury compared to those who do not develop persistent PTH. Furthermore, logistic regression indicated that headache pain intensity at 1–2 weeks and pain inhibitory capacity on the conditioned pain modulation test at 1–2 weeks predicted persistent PTH classification at 4 months post injury. Conclusions Overall, the results suggested that persistent PTH is characterized by dysfunctional alterations in endogenous pain modulatory function and psychological processes in the early stages following mild TBI, which likely exacerbate risk for the maintenance of PTH.

scholarly journals Central inhibition of pain is augmented in women with self-injurious behavior

2021 ◽  
Author(s):  
Maria Lalouni ◽  
Jens Fust ◽  
Johan Bjureberg ◽  
Granit Kastrati ◽  
Robin Fondberg ◽  
...  
Keyword(s):  
Temporal Summation ◽  
Pain Modulation ◽  
Pain Tolerance ◽  
Conditioned Pain Modulation ◽  
Heat Pain ◽  
Healthy Controls ◽  
Down Regulation ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Pressure Pain Thresholds

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated higher pain thresholds and tolerance compared with individuals without NSSI. The objective of the study was to assess which aspects of the pain regulatory system that account for this augmented pain perception. In a cross-sectional design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Thermal pain stimuli were assessed during fMRI scanning and NSSI behaviors and clinical symptoms were self-assessed. NSSI participants demonstrated higher pain thresholds during heat and pressure pain compared to controls. During conditioned pain modulation, NSSI participants showed a more effective central down-regulation of pain for NSSI participants. Temporal summation did not differ between the groups. There were no correlations between pain outcomes and NSSI behaviors or clinical characteristics. The fMRI analyses revealed increased activity in the primary and secondary somatosensory cortex in NSSI participants, compared to healthy controls, which are brain regions implicated in sensory aspects of pain processing. The findings suggest segregated inhibitory mechanisms for pain and emotion in NSSI, as pain insensitivity was linked to enhanced inhibitory control of pain in spite of significant impairments in emotion regulation. This may represent an endophenotype associated with a greater risk for developing self-injurious behavior.

scholarly journals A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia

2018 ◽  
Vol 12 (4) ◽  
pp. 250-256 ◽  
Author(s):  
Theresa Wodehouse ◽  
Kavita Poply ◽  
Shankar Ramaswamy ◽  
Saowarat Snidvongs ◽  
Julius Bourke ◽  
...  
Keyword(s):  
Pilot Study ◽  
Quantitative Sensory Testing ◽  
Fibromyalgia Impact Questionnaire ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Sensory Testing ◽  
Central Sensitisation ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Pressure Pain Thresholds

Background: Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. Methods: A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. Results: Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. Conclusion: This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly ‘dynamic responses’, has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.

CGRP monoclonal antibody prevents the loss of diffuse noxious inhibitory controls (DNIC) in a mouse model of post-traumatic headache

Cephalalgia ◽  
2021 ◽  
pp. 033310242098168
Author(s):  
Caroline M Kopruszinski ◽  
Joelle M Turnes ◽  
Juliana Swiokla ◽  
Troy J Weinstein ◽  
Todd J Schwedt ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inhibitory Control ◽  
Mild Traumatic Brain Injury ◽  
Pain Modulation ◽  
Diffuse Noxious Inhibitory Controls ◽  
Diffuse Noxious Inhibitory Control ◽  
Cutaneous Allodynia ◽  
Calcitonin Gene ◽  
Post Traumatic

Aim Determine the role of calcitonin-gene related peptide in promoting post-traumatic headache and dysregulation of central pain modulation induced by mild traumatic brain injury in mice. Methods Mild traumatic brain injury was induced in lightly anesthetized male C57BL/6J mice by a weight drop onto a closed and unfixed skull, which allowed free head rotation after the impact. We first determined possible alterations in the diffuse noxious inhibitory controls, a measure of net descending pain inhibition called conditioned pain modulation in humans at day 2 following mild traumatic brain injury. Diffuse noxious inhibitory control was assessed as the latency to a thermally induced tail-flick that served as the test stimulus in the presence of right forepaw capsaicin injection that provided the conditioning stimulus. Post-traumatic headache-like behaviors were assessed by the development of cutaneous allodynia in the periorbital and hindpaw regions after mild traumatic brain injury. We then determined if intraperitoneal fremanezumab, an anti-calcitonin-gene related peptide monoclonal antibody or vehicle administered 2 h after sham or mild traumatic brain injury induction could alter cutaneous allodynia or diffuse noxious inhibitory control responses on day 2 post mild traumatic brain injury. Results In naïve and sham mice, capsaicin injection into the forepaw elevated the latency to tail-flick, reflecting the antinociceptive diffuse noxious inhibitory control response. Periorbital and hindpaw cutaneous allodynia, as well as a loss of diffuse noxious inhibitory control, was observed in mice 2 days after mild traumatic brain injury. Systemic treatment with fremanezumab blocked mild traumatic brain injury-induced cutaneous allodynia and prevented the loss of diffuse noxious inhibitory controls in mice subjected to a mild traumatic brain injury. Interpretation Sequestration of calcitonin-gene related peptide in the initial stages following mild traumatic brain injury blocked the acute allodynia that may reflect mild traumatic brain injury-related post-traumatic headache and, additionally, prevented the loss of net descending inhibition within central pain modulation pathways. As loss of conditioned pain modulation has been linked to multiple persistent pain conditions, dysregulation of descending modulatory pathways may contribute to the persistence of post-traumatic headache. Additionally, evaluation of the conditioned pain modulation/diffuse noxious inhibitory controls response may serve as a biomarker of vulnerability for chronic/persistent pain. These findings suggest that early anti-calcitonin-gene related peptide intervention has the potential to be effective both for the treatment of mild traumatic brain injury-induced post-traumatic headache, as well as inhibiting mechanisms that may promote post-traumatic headache persistence.

scholarly journals Exploring the pain in patellofemoral pain: A systematic review and meta-analysis examining signs of central sensitization

2020 ◽  
Author(s):  
Kemery J. Sigmund ◽  
Marie K. Hoeger Bement ◽  
Jennifer E. Earl-Boehm
Keyword(s):  
Systematic Review ◽  
Central Sensitization ◽  
Temporal Summation ◽  
Meta Analysis ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Pressure Pain Thresholds ◽  
Pain Mapping

Objective: Patellofemoral pain has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyper responsive. Research in this area in PFP has been increasingly productive in the past decade. The aim of this review is to determine whether evidence supports manifestations of central sensitization in individuals with PFP. Data sources: MeSH terms for quantitative sensory testing (QST) pressure pain thresholds, conditioned pain modulation, temporal summation, sensitization, hyperalgesia, and anterior knee pain or PFP were searched in PubMed, SportDiscus, CINAHL, Academic Search Complete, and Ebscohost. Study Selection: Peer reviewed studies written in English, published between 2005–2020 which investigated QST and/or pain mapping in a sample with PFP were included in this review. Data Extraction: The initial search yielded 140 articles. After duplicates were removed, 78 article abstracts were reviewed. Full-text review of 21 studies occurred, with 11 studies included in the meta-analysis and eight studies included in the systematic review. Data Synthesis: A random-effects meta-analysis was conducted for four QST variables (local pressure pain thresholds, remote pressure pain thresholds, conditioned pain modulation, temporal summation). Strong evidence supports lower local and remote pressure pain thresholds, impaired conditioned pain modulation, and facilitated temporal summation in individuals with PFP compared to pain-free individuals. Conflicting evidence is presented for heat and cold pain thresholds. Pain mapping demonstrated expanding pain patterns associated with long PFP symptom duration. Conclusions: Signs of central sensitization are present in individuals with PFP, indicating altered pain modulation. PFP etiological and treatment models should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically and treatments with central effects should be considered as part of a multi-modal plan of care. Registration Number: This review is registered with Prospero (CRD42019127548) Registration URL: https://www.crd.york.ac.uk/PROSPERO Key Points:

scholarly journals Pathophysiological links between traumatic brain injury and post-traumatic headaches

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2116 ◽  
Author(s):  
Robert L. Ruff ◽  
Kayla Blake
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Pain Modulation ◽  
Neural Systems ◽  
Depression And Anxiety ◽  
Post Traumatic Stress ◽  
Psychological Conditions ◽  
Headache Severity ◽  
Perceived Pain ◽  
Post Traumatic

This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD.

Time Interval Between Traumatic Brain Injury And Post Traumatic Epilepsy

2013 ◽  
Vol 21 (2) ◽  
pp. 222-228
Author(s):  
Daniel Garbin Di Luca ◽  
Glenda Corrêa Borges de Lacerda
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
First Year ◽  
Time Interval ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Post Traumatic ◽  
Faster Development ◽  
Post Traumatic Epilepsy ◽  
Traumatic Epilepsy

Introduction. The estimated time interval in which an individual can develop Post Traumatic Epilepsy (PTE) after a traumatic brain injury (TBI) is not clear. Objective. To assess the possible influence of the clinical features in the time interval between TBI and PTE develop­ment. Method. We analyzed retrospectively 400 medical records from a tertiary Brazilian hospital. We selected and reevaluated 50 patients and data was confronted with the time between TBI and PTE devel­opment by a Kaplan-Meier survival analysis. A Cox-hazard regression was also conducted to define the characteristics that could be involved in the latent period of the PTE development. Results. Patients devel­oped PTE especially in the first year (56%). We found a tendency of a faster development of PTE in patients older than 24 years (P<0.0001) and in men (P=0.03). Complex partial seizures evolving to generalized seizures were predominant in patients after moderate (37.7%) and severe (48.8%) TBIs, and simple partial seizures evolving to general­ized seizures in mild TBIs (45.5%). Conclusions. Our data suggest that the first year after a TBI is the most critical period for PTE de­velopment and those males older than 24 years could have a faster development of PTE.

Association of Ventilation during Initial Trauma Resuscitation for Traumatic Brain Injury and Post-Traumatic Outcomes: A Systematic Review

2021 ◽  
pp. 1-6
Author(s):  
Mary Beth Howard ◽  
Nichole McCollum ◽  
Emily C. Alberto ◽  
Hannah Kotler ◽  
Mary E. Mottla ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Trauma Resuscitation ◽  
Cerebral Herniation ◽  
Full Text Review ◽  
Post Traumatic ◽  
Ventilation Strategies ◽  
End Tidal

Abstract Objectives: In the absence of evidence of acute cerebral herniation, normal ventilation is recommended for patients with traumatic brain injury (TBI). Despite this recommendation, ventilation strategies vary during the initial management of patients with TBI and may impact outcome. The goal of this systematic review was to define the best evidence-based practice of ventilation management during the initial resuscitation period. Methods: A literature search of PubMed, CINAHL, and SCOPUS identified studies from 2009 through 2019 addressing the effects of ventilation during the initial post-trauma resuscitation on patient outcomes. Results: The initial search yielded 899 articles, from which 13 were relevant and selected for full-text review. Six of the 13 articles met the inclusion criteria, all of which reported on patients with TBI. Either end-tidal carbon dioxide (ETCO2) or partial pressure carbon dioxide (PCO2) were the independent variables associated with mortality. Decreased rates of mortality were reported in patients with normal PCO2 or ETCO2. Conclusions: Normoventilation, as measured by ETCO2 or PCO2, is associated with decreased mortality in patients with TBI. Preventing hyperventilation or hypoventilation in patients with TBI during the early resuscitation phase could improve outcome after TBI.

scholarly journals Depression following traumatic brain injury: a comprehensive overview

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Marc Fakhoury ◽  
Zaynab Shakkour ◽  
Firas Kobeissy ◽  
Nada Lawand
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Health Concern ◽  
First Year ◽  
Comprehensive Overview ◽  
Symptoms Of Depression ◽  
Current State ◽  
Post Traumatic ◽  
Brain Changes

Abstract Traumatic brain injury (TBI) represents a major health concern affecting the neuropsychological health; TBI is accompanied by drastic long-term adverse complications that can influence many aspects of the life of affected individuals. A substantial number of studies have shown that mood disorders, particularly depression, are the most frequent complications encountered in individuals with TBI. Post-traumatic depression (P-TD) is present in approximately 30% of individuals with TBI, with the majority of individuals experiencing symptoms of depression during the first year following head injury. To date, the mechanisms of P-TD are far from being fully understood, and effective treatments that completely halt this condition are still lacking. The aim of this review is to outline the current state of knowledge on the prevalence and risk factors of P-TD, to discuss the accompanying brain changes at the anatomical, molecular and functional levels, and to discuss current approaches used for the treatment of P-TD.

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