Journal article
Pretreatment with an anti-CGRP monoclonal antibody attenuates mild TBI-induced tactile hypersensitivity in mice
Journal of headache and pain, Vol.26(1), 175
08/04/2025
DOI: 10.1186/s10194-025-02108-x
PMCID: PMC12323213
PMID: 40760469
Abstract
Background
Post-traumatic headache (PTH) can develop following a mild traumatic brain injury (mTBI), such as a concussion. It is especially common among active-duty military personnel, Veterans, and athletes. The high prevalence and chronic nature of PTH highlight the importance of studying these conditions in animal models to develop new, effective treatments. Since the symptoms associated with PTH resemble those of migraine, we focused on the neuropeptide calcitonin gene-related peptide (CGRP) as a potential therapeutic target.
Methods
We used a mouse model of mTBI involving three repeated closed head impacts to assess the therapeutic efficacy of a monoclonal antibody (mAb) that blocks CGRP. To validate the model, we first assessed and optimized the development of periorbital and plantar tactile hypersensitivity in outbred CD1 mice. We then tested these responses after intraperitoneal injection of two migraine triggers: CGRP and sodium nitroprusside (SNP), a nitric oxide donor. Then, we assessed the efficacy of the anti-CGRP mAb using different administration paradigms.
Results
Early administration of an anti-CGRP mAb before induction of TBI did not fully prevent the initial transient periorbital tactile hypersensitivity observed following multiple closed head injuries. However, the mAb did partially reduce persistent periorbital tactile hypersensitivity to a sub-threshold trigger. Administration of the mAb immediately after the injuries was also able to partially reduce persistent hypersensitivity. Importantly, injection of the anti-CGRP mAb 24 h prior to injection of a sub-threshold dose of CGRP or SNP fully prevented periorbital hypersensitivity to these triggers during the persistent sensitivity phase.
Conclusions
These results indicate that an anti-CGRP mAb can partially, but not fully, attenuate cephalic tactile hypersensitivity when administered immediately before or after the mTBI event. In contrast, a stronger rescue was seen when the anti-CGRP mAb was administered just prior to CGRP and nitric oxide triggers. Thus, depending on the timing of administration, the anti-CGRP mAb can block persistent sensitization to headache triggers after mTBI.
Details
- Title: Subtitle
- Pretreatment with an anti-CGRP monoclonal antibody attenuates mild TBI-induced tactile hypersensitivity in mice
- Creators
- Anne-Sophie Wattiez - Center for Scientific ReviewAdisa Kuburas - University of IowaWilliam C Castonguay - University of IowaKim Fejgin - LundbeckIb V Klewe - LundbeckAndrew F Russo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of headache and pain, Vol.26(1), 175
- DOI
- 10.1186/s10194-025-02108-x
- PMID
- 40760469
- PMCID
- PMC12323213
- NLM abbreviation
- J Headache Pain
- ISSN
- 1129-2377
- eISSN
- 1129-2377
- Publisher
- BMC
- Grant note
- R01 NS075599 / NINDS NIH HHS I01 RX003523 / RRD VA R01 NS075599 / NIH HHS I01 RX003523-01 / Iowa City Veterans Affairs Medical Center
- Language
- English
- Date published
- 08/04/2025
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984944724202771
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