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Functional neuroanatomy of spinal nociceptive pathways

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TAG: spinal dorsal horn, dorsal root ganglia, neurotrophic factors, neuropeptides, nociception

Our research group investigates the organization and function of spinal nociceptive pathways by combining morphological and functional approaches with particular attention to the mechanisms involved in the transmission of nociceptive input between first and second order sensory neurons in the superficial dorsal horn of the murine spinal cord.
The spinal dorsal horn is a key integration site for nociceptive information transmitted from the periphery to the brain. Both primary sensory neurons in the dorsal root ganglia (DRG) and second order neurons in the dorsal horn are highly heterogeneous. Different populations of sensory neurons can be identified based on the pattern of co-localization/co-expression of neurotransmitters and neuromodulators. Each of these cell populations likely play a specific role in the transmission and modulation of nociceptive input. The scenario is further complicated by bidirectional interactions between neuron and non-neuronal cells.
Our main goal is to understand how these different cell populations and the molecules released intervene in shaping the processing of nociceptive information under normal conditions. In addition, we investigate how the alterations of these mechanisms concur to determine pathological conditions characterized by chronic pain, such as diabetic neuropathy or inflammatory pain. In our investigations, we combine morphological analysis by confocal and electron microscopy and functional investigations by patch clamp recording and calcium imaging. Understanding structural and functional relationship in nociceptive circuits is the necessary premise to correctly interpret alterations in pathological pain conditions. 
 
Specific research lines include:
  • role of neurotrophic factors in nociceptive pathways,
  • mechanisms of spinal inhibitory transmission and disinhibition,
  • neuron-glia interaction in DRGs and in the spinal dorsal horn

  • Mesenchymal stem/stromal cell (MSC) regulation of neuroinflammation and nociception. NC3Rs - (CRACK IT solutions) 2017.
  • Contributo per studio dei meccanismi biologici coinvolti nella neuropatia diabetica. Fondazione CRT 2015.

  • Merighi A. - The histology, physiology, neurochemistry and circuitry of the substantia gelatinosa Rolandi (lamina II) in mammalian spinal cord. - Prog Neurobiol. 2018, 169:91-134.
  • Ferrini F., Lorenzo L.-E., Godin A.G., Quang M.L., De Koninck Y. - Enhancing KCC2 function counteracts morphine-induced hyperalgesia. - Sci Rep. 2017, 7(1):3870.
  • Salio C., Merighi A., Bardoni R. - GABA(B) receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn. - Mol Pain. 2017, 13:1744806917710041.
  • Salio C., Ferrini F. - BDNF and GDNF expression in discrete populations of nociceptors. - Ann Anat. 2016, 207:55-61.
  • Juif P.E., Salio C., Zell V., Melchior M., Lacaud A., Petit-Demouliere N., Ferrini F., Darbon P., Hanesch U., Anton F., Merighi A., Lelièvre V., Poisbeau P. - Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to neonatal maternal deprivation. - Eur J Neurosci. 2016, 44(3):1952-62.
  • Salio C., Ferrini F., Muthuraju S., Merighi A. - Presynaptic modulation of spinal nociceptive transmission by glial cell line-derived neurotrophic factor (GDNF). - J Neurosci. 2014,34(41):13819-33.
  • Ferrini F., Trang T., Mattioli T.A., Laffray S., Del'Guidice T., Lorenzo L.-E., Castonguay A., Doyon N., Zhang W., Godin A.G., Mohr D., Beggs S., Vandal K., Beaulieu J.M., Cahill C.M., Salter M.W., De Koninck Y. - Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl⁻ homeostasis. - Nat Neurosci. 2013, 16(2):183-92.

  • Prof. Yves de Koninck, CERVO (Brain research center), Université Laval, Quebèc (Canada)
  • Prof. Pierrick Poisbeau, Institut des Neurosciences Cellulaires et Intégratives, Université de Strasbourg, Strasbourg
  • Dr. Aziz Moqrich, Institut de Biologie du Développement de Marseille Luminy, CNRS-Université de la Méditerranée, Marseille Cedex (France)
  • Prof. Eustace Johnson, Department of Biological Sciences, Faculty of Medicine, Dentistry and Life Sciences, University of Chester, Chester (UK)
  • Prof. Rita Bardoni, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena (Italy)

Last update: 13/12/2021 16:02
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