[24] In the present study, we show the innervation pattern of these extracranially projecting afferents in more detail. We found labeled nerve fibers not only within the deep structures of the masticatory muscles and upper neck muscles but also within the connective tissue of the temporomandibular joint. Since we have never seen stained structures other than nerves in the dura

mater, as well as in sutures and emissary canals, we are FDA-approved Drug Library high throughput sure that the tracer did not freely diffuse to these extracranial tissues. In the nuchal region, the trigeminal innervation territory seems to overlap with the territory of the occipital nerves. The innervation of pericranial muscles by collaterals of meningeal afferent fibers seems to be fairly substantial. The labeled extracranial nerve fibers in this region are certainly not of spinal origin because staining was completely lacking in the occipital nerves. Although we observed, both in humans and rats, nerves fibers in the posterior Ibrutinib ic50 part of the cranial cavity that penetrate the petrosquamous fissure, we could confirm labeled

nerve fibers in the upper neck muscles only in rats, due to the limited diffusion distance of the postmortem tracing technique. The electron microscopic sections of the spinosus nerve both in rat and human specimens showed numerous myelinated nerve fibers, which according to their diameter must partly be classified as Aβ-fibers, confirming previous observations.[9, 12, 20] Aβ-fibers subserve normally mechanoreceptive functions, but it seems difficult to attribute meningeal afferents a non-nociceptive function since there is no sensation but pain see more that could be evoked by stimulation of the dura

mater during head surgeries.[5, 6] It has been speculated that these nerve fibers could be activated by mechanical stimuli, such as sudden head movements.[12, 36] This idea is particularly interesting in respect of their possible contribution to migraine and chronic tension-type headaches, if these nerve fibers belong to those that innervate pericranial muscles. To clarify the nociceptive nature of these afferents, combined labeling with nociceptive markers like neuropeptides may be useful, but first trials using antibodies against calcitonin gene-related peptide to label retrogradely traced nerve fibers have failed, probably due to the long duration of tissue fixation. Apart from the above hypothesis, there is an additional functional explanation for the extracranial innervation: Possibly part of the myelinated nerve fibers innervating pericranial muscles are not collaterals of meningeal afferents but proprioceptive fibers that travel through the trigeminal ganglion toward their somata located in the mesencephalic nucleus of the trigeminal nerve.