RESUMO
Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Dura-Máter , Neurônios , Ratos Sprague-Dawley , Hemorragia Subaracnóidea , Gânglio Trigeminal , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dura-Máter/metabolismo , Masculino , Ratos , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Neurônios/metabolismo , Gânglio Trigeminal/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Nervo Trigêmeo/metabolismoRESUMO
Recently, the transient receptor potential ankyrin 1 (TRPA1) has gained more attention in migraine-related research. The involvement of the TRPA1 receptor in migraine headaches is proposed by the fact that TRPA1 may be a target of some migraine-triggering factors. Although it is doubtful that activation of TRPA1 alone is sufficient to induce pain, behavioral studies have demonstrated that TRPA1 is involved in injury- and inflammation-induced hypersensitivity. Here, we review the functional relevance of TRPA1 in headaches and its therapeutic potential, mainly focusing on its role in the development of hypersensitivity, referring to its altered expression in pathological conditions, and its functional interaction with other TRP channels.
