Molecular Pain Research //
Science

Research Strategies

Elucidating the very early steps of pain signal transduction (to identify and treat pain at the source). For this aim, we are studying the main pain transducers such as TRPV1, TRPA1, P2X and ASIC receptors as well as sodium, potassium and HCN channels in trigeminal neurons at rest and during neuronal sensitization.

  • Understanding the cross-talks between meningeal vessels, glial, neuronal and immune cells in the sensitization of the trigemino-vascular system.
  • We apply a battery of modern experimental approaches to address pain mechanisms at molecular, cellular and in vivo levels. These methods include:
    • live imaging (in vivo and in vitro)
    •  electrophysiological recordings from isolated neurons and brain slices
    •  molecular biology tools and biochemical assays
    •  flow cytometry
    •  molecular and kinetic modeling
    • our toolbox of electrophysiological methods includes a unique approach to record nociceptive signals from the periphery of the trigeminal nerve in meninges (the place from where migraine pain originates).
  • In addition to using animal models of migraine, we also collaborate with clinicians to study migraine in patients and perform translational studies.
  • Based on our findings we plan to identify the best targets for pain relief and, in collaboration with local chemists, to develop new pain-relieving medicines (producing intellectual property).
  • Our aim also to develop further our already very active collaboration at National and International levels with research groups from Italy, UK, Germany, Russia, Czech Republic and France.

Selected Projects

Studies on P2X7 pore opening

Overlap histograms of the direct pore opening on native P2X7 receptors from SGC culture (FACS) and Electrophysiology trace (Patch-Clamp) of the pore opening on recombinant Rat P2X7 in HEK cells (Ishchenko Y.)

In Vitro Migraine studies

Electrophysiological recording from meningeal afferents (Rat hemiscul)

Zakharov et al., Front Cell Neurosci. 2015 

Molecular modelling

Molecular Models of the P2X3 structure of the receptors and “left flipper”

Petrenko et al.,  Biochemistry. 2011

Selected publications

  1. Viatchenko-Karpinskij V.*, Novosolova N.*, Ishchenko Ye.*, Ameruddin A., WrightM., Tsintsadze V., Kamal A., Burnashev N., Miller A.D, Voitenko N., Giniatullin R.and Lozovaya N.,  Stable, synthetic analogues of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain., J. Molecular Pain, Accepted: December 2015, MS:1083732176112671 (*authors with same contribution)
  2. Zakharov A, Vitale C, Kilinc E, Koroleva K, Fayuk D, Shelukhina I, Naumenko N, Skorinkin A, Khazipov R, Giniatullin R. Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers. Front Cell Neurosci. 2015 Jul 28;9:287. doi: 10.3389/fncel.2015.00287. eCollection 2015.
  3.  Shatillo A, Salo RA, Giniatullin R, Gröhn OH. Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI. Neuropharmacology. 2015 Jun;93:164-70. doi: 10.1016/j.neuropharm.2015.01.028. Epub 215 Feb 14.
  4.  Pryazhnikov E, Kislin M, Tibeykina M, Toptunov D, Ptukha A, Shatillo A, Grohn O, Giniatullin R, Khiroug L. Opposite Reactivity of Meningeal versus Cortical Microvessels to the Nitric Oxide Donor Glyceryl Trinitrate Evaluated In Vivo with Two-Photon Imaging. PLoS One. 2014 Feb 28;9(2):e89699. doi: 10.1371/journal.pone.0089699.
  5.  Abushik PA, Niittykoski M, Giniatullina R, Shakirzyanova A, Bart G, Fayuk D, Sibarov DA, Antonov SM, Giniatullin R. The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and corticalneurons and glial cells. J Neurochem. 2013 Nov 24. doi: 10.1111/jnc.12615.
  6.  Shatillo A, Koroleva K, Giniatullina R, Naumenko N, Slastnikova AA, Aliev RR,  Bart G, Atalay M, Gu C, Khazipov R, Davletov B, Grohn O, Giniatullin R. Cortical  spreading depression induces oxidative stress in the trigeminal nociceptive system. Neuroscience. 2013 Dec 3;253:341-9. doi: 10.1016/j.neuroscience.2013.09.002.
  7. Zaproudina N, Teplov V, Nippolainen E, Lipponen JA, Kamshilin AA, Narhi M, Karjalainen PA, Giniatullin R. Asynchronicity of facial blood perfusion in migraine. PLoS One. 2013 Dec 4;8(12):e80189. doi: 10.1371/journal.pone.0080189.
  8. Giniatullin R, Nistri A. Desensitization properties of P2X3 receptors shaping  pain signaling. Front Cell Neurosci. 2013 Dec 6;7:245. doi: 10.3389/fncel.2013.00245.
  9. Petrenko N, Khafizov K, Tvrdonova V, Skorinkin A, Giniatullin R. Role of the Ectodomain Serine 275 in Shaping the Binding Pocket of the ATP-Gated P2X3 Receptor. Biochemistry 2011, 50(39): 8427-8436.
  10. Mazzuca M, Minlebaev M, Shakirzyanova A, Tyzio R, Taccola G, Janackova S, Gataullina S, Ben-Ari Y, Giniatullin R, Khazipov R. Newborn Analgesia Mediated by Oxytocin during Delivery. Front Cell Neurosci 2011, 5: 3.