Clinical experience suggests that both PTH and photophobia often occur together, which may suggest a common pathophysiological explanation. Photophobia may be linked to photosensitive retinal ganglion cells and their pathways through the optic nerve, trigeminal nerve, and thalamus. Trauma may cause cortical damage, ocular vasodilation, or other dysfunction in any of these pathways. Significantly, cortical excitability has been reported in other conditions like migraine and epilepsy. Researchers suggest a relationship between cortical damage and PTH symptoms.2
Pathophysiologies Linked to PTH
After an injury to the central nervous system, microglia may assume a pro- or anti-inflammatory role. These cells can release toxic or degradative compounds that harm healthy cells. In addition, damage to the blood-brain barrier can also affect its function or permeability. Pathogens, proteins, or leukocytes may leak through, contributing to further inflammation.2
Calcitonin gene-related peptide (CGRP), a pain-signaling molecule, has been singled out for its role in contributing to inflammation. One mTBI mouse model study demonstrated that increased levels of CGRP were associated with photophobia, and treatment with CGRP antagonists decreased both allodynia and photophobia.2
Some researchers have suggested a peripheral component to PTH. “A model for mTBI on mice study showed that in the acute phase post-mTBI, there was a selective enhancement of nociceptive responses to cranial structures … but not to extracranial structures.”2 The same model revealed evidence of inflammatory changes in deep cranial structures. Thus, PTH may originate from peripheral rather than central pain pathways.
Even mild TBI can result in structural brain matter damage, and damage along pain pathways may lead to central pain. PTH symptoms may, therefore, have a central origin.
Investigators of imaging studies on mTBI patients with PTH migraines appear to support this hypothesis. Advanced MRIs were able to differentiate between these patients and controls. In some cases, MRI results could even identify which patients had migraines based on signs of white matter injury. However, the role of white matter changes in PTH remains unclear.1
Cortical Spreading Depolarization
Cortical Spreading Depolarization (CSD) can interrupt local cortical function for a period lasting from several minutes to several hours. This phenomenon “has been described in several pathological states, such as strokes, epilepsy, intracranial hemorrhages, migraines, and TBI”2 and is linked to a depression in cortical activity along with vasoconstriction.
The researchers noted that TBI “promotes an environment susceptible to CSD”2 and that CSD patients appear to have worse outcomes. Although CSD is a well-documented phenomenon, it is not evident how it applies to the mTBI population. However, it may play a role in severe TBI.