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 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.

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 Altered speech patterns in subjects with post-traumatic headache due to mild traumatic brain injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Catherine D. Chong ◽  
Jianwei Zhang ◽  
Jing Li ◽  
Teresa Wu ◽  
Gina Dumkrieger ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Speech Production ◽  
Mild Traumatic Brain Injury ◽  
Mobile Application ◽  
Speaking Rate ◽  
Mixed Effect ◽  
Effect Model ◽  
Vowel Space ◽  
Post Traumatic

Abstract Background/objective Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design. Results Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free. Conclusions Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.

scholarly journals Structural brain connectivity predicts acute pain after mild traumatic brain injury

2021 ◽  
Author(s):  
Paulo Branco ◽  
Noam Bosak ◽  
Jannis Bielefeld ◽  
Olivia Cong ◽  
Yelena Granovsky ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Acute Pain ◽  
Pain Perception ◽  
Strong Predictor ◽  
Pain Modulation ◽  
Acute Injury ◽  
Post Injury

Mild traumatic brain injury, mTBI, is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute post-injury pain is important since it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 172 patients with mTBI, following a motorized vehicle collision and used a machine learning approach to extract white matter structural and resting state fMRI functional connectivity measures to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamic-cortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in two independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6-months after the collision still predicted mTBI pain at that timepoint (n = 36). These white-matter connections were associated with two nociceptive psychophysical outcomes tested at a remote body site – namely conditioned pain modulation and magnitude of suprathreshold pain–, and with pain sensitivity questionnaire scores. Our validated findings demonstrate a stable white-matter network, the properties of which determine a significant amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.

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