PDE9A, PDE10A, and PDE11A expression in rat trigeminovascular pain signalling system

Activation of the trigeminovascular pain signalling system, including cerebral arteries, meninges, trigeminal ganglion, and brain stem, is involved in migraine. Furthermore, stimulation of cyclic nucleotide (cAMP and cGMP) production as well as inhibition of phosphodiesterases (PDEs) induces headache and migraine. In order to investigate the possible role of PDE in the pain pathway of migraine, expression of the most recently discovered PDE subtypes (9A, 10A and 11A) in cerebral arteries, dura mater, and trigeminal ganglion and nucleus was examined. The presence of mRNA and protein in the middle cerebral artery, basilar artery, meninges, trigeminal ganglion, and spinal trigeminal nucleus of male Sprague-Dawley rats were investigated using real-time PCR, Western blot, and immunohistochemistry. The results were compared to two peripheral arteries: aorta and mesenteric artery, as well as neocortex and cerebellar cortex. Real-time PCR and Western blotting showed that PDE9A, PDE10A and PDE11A are expressed in components of the rat trigeminovascular pain signalling system including middle cerebral artery, basilar artery, meninges, trigeminal ganglion and spinal trigeminal nucleus. Aorta and mesenteric artery as well as cerebral neocortex and cerebellar cortex also showed expression of PDE9A, PDE10A and PDE11A. Immunohistochemistry revealed that PDE9A, PDE10A and PDE11A are localised in the cytosol of nerve cell bodies of the trigeminal ganglion. We here present, for the first time, the expression of PDE9A, PDE10A, and PDE11A in the trigeminovascular system. The functional implications are yet unknown, but their localisation indicates that they may have a role in the pain pathway of migraine as well as trigeminal neuralgia and trigeminal autonomic cephalalgias.