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Pathophysiology of pain, neuroimmunology and drug of abuse Unit  

Lab. Panerai

 

Head
Prof. Alberto.E.Panerai    alberto.panerai@unimi.it

Team
Prof.ssa Paola Sacerdote, Associate professor paola.sacerdote@unimi.it
Silvia Franchi, Post Doc scientist  silvia.franchi@unimi.it
Sarah Moretti, PhD student    sarah.moretti@unimi.it
Mara Castelli, PhD student mara.castelli @unimi.it

 

Research activity

1) Pathophysiology of pain: basic and clinical aspects

2) Stem cells and microvescicles as therapeutic approach to pain

3) Drug of abuse and immunomodulation: basic mechanism and clinical impact. 

1) The laboratory is involved in the study of the mechanisms at the basis of onset, maintenance and resolution of chronic inflammatory and neuropathic pain. We and others recently demonstrated that a pathological interaction between neurons, glia, microglia and immune cells in the peripheral and central nervous system underlies the chronicization of pain. Our research aims at identifying the molecular and cellular mechanisms and the main determinants at the basis of neuroinflammatory processes in the  nervous system sites involved in pain transmission, focussing on the pro-anti-inflammatory cytokine balance. A deep understanding of these interactions may indicate novel therapeutic targets for treating neuropathic pain, that is refractory to most known analgesics.

2) Stem cells of different origin for their intrinsic ability to home in the lesioned tissue can be an important tool to modulate the activity of resident cells , also along the pathways involved in pain transmission. These cells can cross-talk with the resident environment by releasing trophic factors, hormones and immune factors as well as by direct cell to cell contact. Microvescicles, that can be produced and shedded by stem cells, have been demonstrated to be the carriers of most mRNA and factors. The administration of stem cell derived microvescicles can be an innovative therapeutic approach , since they can be used instead of stem cells, avoiding the risks related to a cellular therapy.
The study of stem cells and microvescicles application to pain, can be of relevance also for fields not directly linked to regenerative medicine.

3) Marijuana and opioids are wide spread substances of abuse, that induce a large range of diverse effects. These substances target different receptors, alter functionality of different organs and systems and have different mechanisms of actions. However a common aspect is their ability to modify the immune system responses. Our laboratory evaluates the effects that opioids and cannabis derivatives have on immune responses, both in vitro and in vivo in the human and in animal models, in order to identify their effect on health. Moreover opioids, and more recently cannabinoids, besides being drugs of abuse are used for treating pain and other conditions in the human. Therefore it is of great importance to evaluate the potential immunomodulatory activity of therapeutic doses of these drugs in order to improve their clinical use. 

 

Methods

Behavioural laboratory for the evaluation of  nociception, allodynia and hyperalgesia

Animal models of inflammatory and neuropathic pain

Cellular immunology (lymphoproliferation, chemotaxis, cytokine production,antibody production)

Western blotting

Elisa

Quantitative Rt-PCR

Cytofluorimetry

 

Selected publications

1. SACERDOTE P, FRANCHI S, MORETTI S, CASTELLI M, PROCACCI P, MAGNAGHI V, PANERAI AE. Cytokine Modulation is Necessary for Efficacious Treatment of Experimental Neuropathic Pain. J NEUROIMMUNE PHARMACOL. 2013 ;8:202-11.

2. SACERDOTE P, NIADA S, FRANCHI S, ARRIGONI E, ROSSI A, YENAGI V, DE GIROLAMO L, PANERAI AE, BRINI AT. Systemic administration of human Adipose-derived Stem Cells (hASCs) reverts nociceptive hypersensitivity in an experimental model of neuropathy.STEM CELLS DEV. 2012 NOV 29.

3. FRANCHI S, VALSECCHI AE, BORSANI E, PROCACCI P, FERRARI D, ZAFFA C, SARTORI P, RODELLA LF, VESCOVI A, MAIONE S, ROSSI F, COLLEONI M, SACERDOTE P, PANERAI AE. Intravenous Neural Stem Cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy. PAIN 153:850-861 2012

4. FRANCHI S, MORETTI S, CASTELLI M, LATTUADA D, SCAVULLO C, PANERAI AE. SACERDOTE P. Mu opioid receptor activation modulates Toll like receptor 4 in murine macrophage BRAIN BEHAVIOR IMMUNITY, 26:480-488, 2012

5. LATTANZI R, SACERDOTE P, FRANCHI S, CANESTRELLI M, MIELE R, BARRA D, VISENTIN S, DENUCCIO C, PORRECA F, DE FELICE M, GUIDA F, LUONGO L, DE NOVELLIS V, MAIONE S AND NEGRI L. Pharmacological activity of a BV8 analog modified in position 24 BR J PHARMACOL. 2011

6. VALSECCHI AE, 6. FRANCHI S, PANERAI AE, ROSSI A, SACERDOTE P, COLLEONI M. The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model EUR. J. PHARMACOL, - 650: 694-702. 2011

7. SACERDOTE P, COLLEONI M. Murine model of human neuropathic pain: molecular basis of disease BIOCHEMICAL BIOPHYSICAL ACTA 1802 :924-933 2010 

8. FRANCHI S, SACERDOTE P, MORETTI S, GERRA G, LECCESE V, TALLONE MV, PANERAI A, SOMAINI L. The effects of alcholism pharmacotherapy on immune responses in alchol dependent patients. INTERNATIONAL JOURNAL OF          IMMUNOPATHOLOGY AND PHARMACOLOGY 23:847-855, 2010

9. GIANNINI E, LATTANZI R, NICOTRA A, CAMPESE AF, GRAZIOLI P, SCREPANTI I, BALBONI G,SALVADORI S, SACERDOTE P, NEGRI L. The chemokine Bv8/prokineticin 2 is up- regulated in inflammatory granulocytes and modulates inflammatory pain. Proc Natl Acad Sci U S A. 2009 106:14646-51

10. VALSECCHI AE, FRANCHI S, PANERAI AE, SACERDOTE P, TROVATO AE, COLLEONI M. Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: anti-inflammatory and antioxidant activity. JOURNAL NEUROCHEMISTRY. 107:  230-240  2008

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