Trigeminal satellite cells modulate neuronal responses to triptans: relevance for migraine therapy.
In the present paper, we have further developed an in vitro model to study neuronal-glial interaction at trigeminal level by characterizing the effects of conditioned medium (CM) collected from activated primary cultures of satellite glial cells (SGCs) on calcitonin gene-related peptide (CGRP) release from rat trigeminal neurons. Moreover, we investigated whether such release is inhibited by a clinically relevant anti-migraine drug, sumatriptan. CM effects were tested on trigeminal neuronal cultures in different conditions of activation and at different time points. Long-term exposures of trigeminal neurons to CM increased directly neuronal CGRP release, which was further enhanced by the exposure to capsaicin. In this framework, the anti-migraine drug sumatriptan was able to inhibit the evoked CGRP release from naïve trigeminal neuron cultures, as well as from trigeminal cultures pre-exposed for 30 min to CM. On the contrary, sumatriptan failed to inhibit evoked CGRP release from trigeminal neurons after prolonged (4 and 8 h) pre-exposures to CM. These findings were confirmed in co-culture experiments (neurons and SGCs), where activation of SGCs or a bradykinin priming were used. Our data demonstrate that SGCs activation could influence neuronal excitability, and that this event affects the neuronal responses to triptans.
Institute of Pharmacology, Catholic University of Sacred Heart, 00168 Rome, Italy.
Alice
A
de Corato
Alessandro
A
Capuano
Diego
D
Currò
Giuseppe
G
Tringali
Pierluigi
P
Navarra
Cinzia
C
Dello Russo
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D027161:Satellite Cells, Perineuronal / Q000187:drug effects / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology*; D014363:Tryptamines / Q000494:pharmacology* / Q000627:therapeutic use
D017077:Culture Media, Conditioned; D014363:Tryptamines; D015740:Calcitonin Gene-Related Peptide