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Effects of LPA injection into the cisterna magna, trigeminal ganglion and inferior alveolar nerve on the Von Frey test and c-Fos expression

2007; Elsevier BV; Volume: 58; Linguagem: Inglês

10.1016/j.neures.2007.06.774

1872-8111

Yusuke Sakai, Shinichi Sugiyo, Takashi Shimoda, Aya Masawaki, Masayuki Moritani, Atsushi Yoshida, Motohide Takemura,

Pain Mechanisms and Treatments

In intracranial structures unmyelinated C- and Aδ-fibers of the trigeminal nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis (Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called trigeminovascular system) and contain vasoactive neuropeptides (calcitonin gene-related peptide, substance P and neurokinin A). Activation of the trigeminovascular system promotes a meningeal sterile inflammatory response through the release of neuropeptides by peripheral endings. Orthodromic conduction along trigeminovascular fibers transmits information centrally with induction of immediate early c-fos gene within post-synaptic Sp5C neurons, as a marker of neuronal activity within central nociceptive pathways. In laboratory animals the system is activated by either electrical stimulation of the TG, chemical stimulation of the meninges, electrical or mechanical stimulation of the superior sagittal sinus or by induction of cortical spreading depression. All these techniques induce c-fos within Sp5C and are used as a rodent/feline model of vascular headache in humans. Up-to-date there is evidence that at least ten receptors (5-HT1B, 5-HT1D, 5-HTlF, 5-HT2B, NK-1, GABAA, NMDA, AMPA, class III metabotropic glutamate receptors, and opioids μ receptors) modulate c-fos expression within Sp5C. These receptors represent potential targets for anti-migraine drugs as shown by triptans (5-HT1B/1D/1F) and ergot alkaloids (5-HT1A1B/1D/1F). This review discusses the importance of c-fos expression within Sp5C as a marker of cephalic nociception, the different cephalic pain models that induce c-fos within Sp5C, the receptors involved and their potential role as targets for anti-migraine drugs.