Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system

Tuka, Bernadett; Helyes, Zsuzsanna; Mark, Laszlo; Bagoly, Teréz; Németh, József; Márk, László; Brubel, Réka; Reglődi, Dóra; Párdutz, Árpád; Szolcsányi, Janós; Vécsei, László; Tajti, János

doi:10.1016/j.peptides.2011.12.019

Cited by 67 publications

(75 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, despite the presence of mRNA for each receptor in the trigeminal ganglion, it seems unlikely that PACAP-38-induced neuronal changes are mediated via actions at the primary afferent neuron. These data are supported by previous studies that demonstrate that NTG or stimulation of the trigeminal ganglion only produces PACAP-38 release in the TNC, and not the trigeminal ganglion (30). Although these receptor antagonists are likely to act on peripheral sites, it was not known whether they cross the blood-brain barrier.…”

Section: Discussionsupporting

confidence: 77%

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

2015

View full text Add to dashboard Cite

The pathogenesis of migraine is not well understood. To dissect the relative contributions of endogenous peripheral and central mechanisms in triggering migraine, we examined the effects of two pharmacologically similar, but clinically different, vasodilator neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38), on dural meningeal vessels and the response properties of central trigeminovascular neurons. Both VIP and PACAP-38 caused short-lived meningeal vasodilation mediated by VPAC2 receptors, which did not coincide with activation of central trigeminovascular neurons. Only PACAP-38 caused delayed activation and sensitization of central trigeminovascular neurons, similar to its delayed effects in inducing migraine headache. After a 90-min delay, PACAP-38 induced a robust increase in ongoing spontaneous firing and hypersensitivity to intra- and extracranial somatosensory stimulation, which did not coincide with meningeal vasodilation. Only intravenous delivery of a PAC1 receptor antagonist inhibited the peripheral meningeal vasodilatory effects of dural trigeminovascular nociception, whereas only central (intracerebroventricular) administration of the PAC1 receptor antagonist inhibited dural nociceptive-evoked action potentials in central trigeminovascular neurons. Our data suggest that the endogenous mechanisms of migraine pathogenesis are located within the central nervous system, likely in the trigeminocervical complex, and that the dural meninges and their primary afferent innervation are less likely to contribute to migraine initiation. Furthermore, the PAC1 receptor may be an appropriate molecular target for migraine therapeutics.

show abstract

Section: Discussionsupporting

confidence: 77%

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

2015

View full text Add to dashboard Cite

show abstract

“…PACAP exerts various peripheral effects (Helyes et al, 2007;Nemeth et al, 2006) and it has a pro-nociceptive role in the CNS (Amin et al, 2014;Markovics et al, 2012;Schytz et al, 2009;Tuka et al, 2012). It has functions in neuroinflammation (Helyes et al, 2007) and sensitization (Sandor et al, 2009).…”

Section: Pacapmentioning

confidence: 99%

Migraine and neuropeptides

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Others also showed that PACAP might play a key role in spinal sensitization, and therefore, in the development of neuropathic pain [8,25] through PAC1 receptor activation in the dorsal root ganglia [6,20]. Furthermore, PACAP is likely to have a pivotal pro-nociceptive function in animal models of migraine and also in human migraneurs [29,46,54]. Others suggested that the peripheral nociceptive responses elicited by intradermally administered PACAP are mainly mediated through the VPAC receptors [45].…”

Section: Discussionmentioning

confidence: 99%

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

Self Cite

View full text Add to dashboard Cite

a b s t r a c tPituitary Adenylate-Cyclase Activating Polypeptide (PACAP) and Tac1 gene-encoded tachykinins (substance P: SP, neurokinin A: NKA) are expressed in capsaicin-sensitive nerves, but their role in nociception, inflammation and vasoregulation is unclear. Therefore, we investigated the function of these neuropeptides and the NK 1 tachykinin receptor (from Tacr1 gene) in the partial sciatic nerve ligationinduced traumatic mononeuropathy model using gene deficient (PACAP −/− , Tac1 −/− , and Tacr1 −/− ) mice. Mechanonociceptive threshold of the paw was measured with dynamic plantar aesthesiometry, motor coordination with Rota-Rod and cutaneous microcirculation with laser Doppler imaging. Neurogenic vasodilation was evoked by mustard oil stimulating sensory nerves. In wildtype mice 30-40% mechanical hyperalgesia developed one week after nerve ligation, which was not altered in Tac1−/− and Tacr1mice, but was absent in PACAP −/− animals. Motor coordination of the PACAP −/− and Tac1 −/− groups was significantly worse both before and after nerve ligation compared to their wildtypes, but it did not change in Tacr1−/− mice. Basal postoperative microcirculation on the plantar skin of PACAP −/− mice did not differ from the wildtypes, but was significantly lower in Tac1 −/− and Tacr1 −/− ones. In contrast, mustard oil-induced neurogenic vasodilation was significantly smaller in PACAP −/− mice, but not in Tacr1 −/− and Tac1 −/− animals. Both PACAP and SP/NKA, but not NK 1 receptors participate in normal motor coordination. Tachykinins maintain basal cutaneous microcirculation. PACAP is a crucial mediator of neuropathic mechanical hyperalgesia and neurogenic vasodilation. Therefore identifying its target and developing selective, potent antagonists, might open promising new perspectives for the treatment of neuropathic pain and vascular complications.

show abstract

Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system

Cited by 67 publications

References 101 publications

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

Migraine and neuropeptides

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Contact Info

Product

Resources

About

Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system

Cited by 67 publications

References 101 publications

Neuronal PAC 1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

Neuronal PAC 1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

Migraine and neuropeptides

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Contact Info

Product

Resources

About

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

Neuronal PAC ₁ receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine