Whereas the sensitivity can be explained by sensitization of the nervous system, the underlying causes of altered fecal output and reduced exploratory behavior remain to be determined and point to a global phenomenon affecting the organism as a whole rather than just a single system.
These phenomena suggest that sensitization of the trigeminal system may persist interictally.
The activation and sensitization of the trigeminovascular system by vasoactive neuropeptides might be crucial factors of the migraine pathogenesis [8].
The pain phase is due to peripheral and central sensitization of the trigeminal system, as well as to the release of CGRP, both peripherally and centrally.
Sensitization of the trigeminovascular system has been demonstrated using multiple dural infusions of inflammatory soup [20, 22] so a similar enhancement would be expected with repeated AITC injections.
Although further experiments are necessary to clarify this issue, there are several potential mechanisms, whereby endogenous P2X7 could participate in the sensitization of the trigeminovascular system.
NTG may induce indeed a direct hyperalgesic effect via the formation of nitric oxide (NO) and via CGRP release in the NTC [42, 48], or indirectly via the activation of NOS synthesis at the meningeal level as a consequence of a sensitization of the trigeminovascular system [49 51].
Sensitization of the nociceptive system is one suggested explanation for this problem.
This potential underlying mechanism supports our results, assuming that pain hypersensitivity is a marker of sensitization of the nervous system.
Thus, one could imagine that a unilateral headache syndrome results in sensitization of the trigeminal system, which then facilitates the development of tinnitus.
