Mild TBI induces long-lasting sensitization to pain in mice

Anne-Sophie Wattiez, PhD

AHSAM 2020 - Oral session
Published on August 27, 2020

2 minute listen

6 minute read

Key messages

  • Post-traumatic headache (PTH) following mild traumatic brain injury (mTBI) is debilitating and difficult to diagnose, often presenting the same symptoms as migraine.
  • Symptoms can be studied in mice, but further research is required in animal models to develop new effective PTH treatments.
  • Animal models suggest multifactorial injury induces a persistant generalized phenotype while a closed-head impact injury induces a transient localized phenotype.
  • The results of the study support a causative role of calcitonin gene-related peptide (CGRP) in PTH and potential use of CGRP-targeting drugs for the treatment of PTH in clinical practice.
  • Background

    What do we already know about this topic?
  • Findings

    What does this study add?
  • Perspectives

    How does this study impact clinical practice?
  • Expert commentary

    by Andrew Russo, PhD

Key messages

  • Post-traumatic headache (PTH) following mild traumatic brain injury (mTBI) is debilitating and difficult to diagnose, often presenting the same symptoms as migraine.
  • Symptoms can be studied in mice, but further research is required in animal models to develop new effective PTH treatments.
  • Animal models suggest multifactorial injury induces a persistant generalized phenotype while a closed-head impact injury induces a transient localized phenotype.
  • The results of the study support a causative role of calcitonin gene-related peptide (CGRP) in PTH and potential use of CGRP-targeting drugs for the treatment of PTH in clinical practice.

Background

What do we already know about this topic?

  • PTH is highly prevalent in active and retired military personnel, as well as in sport athletes.
  • 70–90% of TBIs are mild.
  • There is a 2–5 times greater risk of a new TBI after the first one.
  • Patients experience a resolution of acute symptoms within 12 weeks.
  • TBI are heterogeneous with a variable clinical presentation, but more than half of patients suffer from PTH associated with severe tactile allodynia.
  • Mice can be primed by a closed head impact-induced mTBI event, sensitizing them to subsequent migraine triggers.

How was this study conducted?

  • Direct comparison of hypersensitivity induced by two different mice models of mild TBI over 4-9 weeks.
  • A multifactorial injury model (MF) using an over-pressure (30 psi) air blast and a closed head impact model (CHI) dropping a 30g weight onto the intact skull were used.
  • Von Frey filaments were used to stimulate the periorbital facial and plantar paw areas.
  • Single and multiple (three times in one day and three times over three days) injuries were tested.
  • The hypersensitivity response to migraine triggers CGRP and sodium nitroprusside (SNP) were evaluated over 13 weeks.

Findings

What does this study add?

  • Both cephalic and extra-cephalic allodynia started one week after MF-induced TBI, persisting for at least nine weeks.
  • For CHI, a transient cephalic hypersensitivity developed between day one and day five after injury and a long-lasting sensitization to non-noxious migraine triggers in both cephalic and extra-cephalic.
  • Multiple injuries over three days were more deleterious than single of multiple injuries in one day.

Perspectives

How does this study impact clinical practice?

  • Both models reflect the observations in clinical practice that TBI patients experience differences in the quality and persistence of pain.
  • The study results support a causative role of CGRP in PTH and potential use of CGRP-targeting drugs for the treatment of PTH in clinical practice.

Perspectives

How does this study impact clinical practice?

  • Both models reflect the observations in clinical practice that TBI patients experience differences in the quality and persistence of pain.
  • The study results support a causative role of CGRP in PTH and potential use of CGRP-targeting drugs for the treatment of PTH in clinical practice.

This is a highlights summary of an oral session given at the AHSAM 2020 Virtual Annual Scientific Meeting and presented by:

Anne-Sophie Wattiez, PhD
Research Scientist
University of Iowa
Iowa City, Iowa

The content is produced by Infomedica, the official reporting partner of ASHAM 2020 Virtual Annual Scientific Meeting. The summary text was drafted by Goldcrest Medical Writing, reviewed by Marco Vercellino, MD, an independent external expert, and approved by Jessica Ailani, MD, FAHS and Mark J. Burish, MD, PhD, the scientific editors of the program.

The presenting authors of the original session had no part in the creation of this conference highlights summary.

In addition, an expert commentary on the topic has been provided by:

Andrew Russo, PhD
University of Iowa, Iowa City, IA, USA

Andrew Russo, PhD
University of Iowa, Iowa City, IA, USA

Andrew Russo is Professor of Molecular Physiology and Biophysics, and Neurology, at the University of Iowa. Dr. Russo received his PhD in Biochemistry from the University of California, Berkeley, followed by postdoctoral training in molecular neurobiology at UCSD. Dr. Russo’s research is focused on how the neuropeptide CGRP contributes to the altered sensory perception and pain of migraine. The lab uses approaches ranging from epigenetics to mouse behavior. The overall goal of his studies is to develop effective diagnostic and therapeutic strategies for migraine and post-traumatic headache.



Headache
Post-traumatic Headache


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