It is now known that glial cells directly participate to the genesis and maintenance of chronic pain, both in the central and in the peripheral nervous system, through their functional cross-talk with pain-transducing neurons . The whole molecular network at the basis of this neuron-to-glia communication is still largely unknown, and the purinergic system is likely to play a key role in close conjunction with other pain-transducing systems [2, 3]. Therefore, we decided to study the contribution of the G protein-coupled P2Y purinergic receptors in pain transmission in the spinal-trigeminal system both in vitro and in vivo. In primary mixed trigeminal cultures, we showed that the pro-algogenic molecule bradykinin potentiates P2Y receptors expressed by satellite glial cells (SGCs)  through the neuronal release of calcitonin gene related peptide (CGRP), which in turn activates the ERK1/2 pathways in SGCs . Interestingly, in cultures from a genetic mouse model of familial hemiplegic migraine we observed an increased CGRP release and an up-regulation in the number of SGCs showing functional P2Y receptors, suggesting that the role of the purinergic system in neuron-glia crosstalk is even more important under pathological conditions . To study the pro- or anti-algogenic role of specific P2Y receptor subtypes in vivo, we next set up a sub-chronic inflammatory model in vivo by injecting complete Freund adjuvant (CFA) into the temporomandibular joint (TMJ). CFA-injected animals showed mechanical allodynia and TMJ edema, accompanied by a strong increase in the number of reactive SGCs and resident macrophages in the TG, and by microglial activation in the ipsilateral medulla oblongata . We are now evaluating the pro- or anti-algogenic role of specific P2Y-receptor subtypes in pain transduction. Overall, our results suggest that P2Y receptors on glial cells might represent innovative targets for the development of effective analgesic drugs. References  M. Takeda, M. Takahashi, S. Matsumoto. Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neuroscience Biobehavioural Reviews, 33, 784-792, 2009.  D. Donnelly-Roberts, S. McGaraughty, C.C. Shieh, P. Honore, M.F. Jarvis. Painful purinergic receptors. Journal of Pharmacology and Experimental Therapeutics, 324, 409-415, 2009.  G. Villa, M. Fumagalli, C. Verderio, M.P. Abbracchio, S. Ceruti. Expression and contribution of satellite glial cells purinoceptors to pain transmission in sensory ganglia: an update. Neuron Glia Biol, 6, 31-42, 2010.  S. Ceruti, M. Fumagalli, G. Villa, C. Verderio, M.P. Abbracchio. Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium, 43, 576-90, 2008.  S. Ceruti, G. Villa, M. Fumagalli, L. Colombo, G. Magni, M. Zanardelli, E. Fabbretti, C. Verderio, A.M. van den Maagdenberg, A. Nistri, M.P. Abbracchio. Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Cav2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain. J Neurosci, 31, 3638-3649, 2011.  G. Villa, S. Ceruti, M. Zanardelli, G. Magni, L. Jasmin, P.T. Ohara, M.P. Abbracchio. Temporomandibular join inflammation activates glial and immune cells in both the trigeminal ganglia and the spinal trigeminal nucleus. Mol Pain, 6, 89, 2010.
Purinergic neuron/glia communication in the spinal-trigeminal system in vitro and in vivo: implications for basic mechanisms of pain transmission / G. Magni, G. Villa, M. Fumagalli, L. Colombo, M. Zanardelli, E. Fabbretti, C. Verderio, A.M.v.d. Maagdenberg, P.T. Ohara, L. Jasmin, A. Nistri, M.P. Abbracchio, S. Ceruti. ((Intervento presentato al convegno Next Step: la giovane ricerca avanza tenutosi a Milano nel 2011.
|Titolo:||Purinergic neuron/glia communication in the spinal-trigeminal system in vitro and in vivo: implications for basic mechanisms of pain transmission|
|Data di pubblicazione:||2011|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||Purinergic neuron/glia communication in the spinal-trigeminal system in vitro and in vivo: implications for basic mechanisms of pain transmission / G. Magni, G. Villa, M. Fumagalli, L. Colombo, M. Zanardelli, E. Fabbretti, C. Verderio, A.M.v.d. Maagdenberg, P.T. Ohara, L. Jasmin, A. Nistri, M.P. Abbracchio, S. Ceruti. ((Intervento presentato al convegno Next Step: la giovane ricerca avanza tenutosi a Milano nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|