A nonphysiological repair of the lesioned nerve leading to the formation of neurinomas, altered nerve conduction, and spontaneous firing is considered the main cause of the events underlying neuropathic pain. It was investigated whether neural stem cell (NSCs) administration could lead to a physiological nerve repair, thus to a reduction of neuropathic pain symptoms such as hyperalgesia and allodynia in a well-established model of this pain (sciatic nerve chronic constriction injury [CCI]). Moreover, since we and others showed that the peripheral nerve lesion starts a cascade of neuroinflammation-related events that may maintain and worsen the original lesion, the effect of NSCs on sciatic nerve pro- and antiinflammatory cytokines in CCI mice was investigated. NSCs injected intravenously, when the pathology was already established, induced a significant reduction in allodynia and hyperalgesia already 3 days after administration, demonstrating a therapeutic effect that lasted for at least 28 days. Responses changed with the number of administered NSCs, and the effect on hyperalgesia could be boosted by a new NSC administration. Treatment significantly decreased proinflammatory, activated antiinflammatory cytokines in the sciatic nerve, and reduced spinal cord Fos expression in laminae I-VI. Moreover, in NSC-treated animals, a reparative process and an improvement of nerve morphology is present at a later time. Since NSC effect on pain symptoms preceded nerve repair and was maintained after cells had disappeared from the lesion site, we suggest that regenerative, behavioral, and immune NSC effects are largely due to microenvironmental changes they might induce at the lesion site.

Intravenous Neural Stem Cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy / S. Franchi, A. Valsecchi, E. Borsani, P. Procacci, D. Ferrari, C. Zaffa, P. Sartori, L.F. Rodella, A. Vescovi, S. Maione, F. Rossi, M. Colleoni, P. Sacerdote, A. Panerai. - In: PAIN. - ISSN 0304-3959. - 153:4(2012), pp. 850-861. [10.1016/j.pain.2012.01.008]

Intravenous Neural Stem Cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy

S. Franchi
Primo
;
P. Procacci;P. Sartori;M. Colleoni;P. Sacerdote;A. Panerai
2012

Abstract

A nonphysiological repair of the lesioned nerve leading to the formation of neurinomas, altered nerve conduction, and spontaneous firing is considered the main cause of the events underlying neuropathic pain. It was investigated whether neural stem cell (NSCs) administration could lead to a physiological nerve repair, thus to a reduction of neuropathic pain symptoms such as hyperalgesia and allodynia in a well-established model of this pain (sciatic nerve chronic constriction injury [CCI]). Moreover, since we and others showed that the peripheral nerve lesion starts a cascade of neuroinflammation-related events that may maintain and worsen the original lesion, the effect of NSCs on sciatic nerve pro- and antiinflammatory cytokines in CCI mice was investigated. NSCs injected intravenously, when the pathology was already established, induced a significant reduction in allodynia and hyperalgesia already 3 days after administration, demonstrating a therapeutic effect that lasted for at least 28 days. Responses changed with the number of administered NSCs, and the effect on hyperalgesia could be boosted by a new NSC administration. Treatment significantly decreased proinflammatory, activated antiinflammatory cytokines in the sciatic nerve, and reduced spinal cord Fos expression in laminae I-VI. Moreover, in NSC-treated animals, a reparative process and an improvement of nerve morphology is present at a later time. Since NSC effect on pain symptoms preceded nerve repair and was maintained after cells had disappeared from the lesion site, we suggest that regenerative, behavioral, and immune NSC effects are largely due to microenvironmental changes they might induce at the lesion site.
Settore BIO/14 - Farmacologia
Settore BIO/17 - Istologia
2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
panerai pain.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 2.18 MB
Formato Adobe PDF
2.18 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/169763
Citazioni
  • ???jsp.display-item.citation.pmc??? 26
  • Scopus 71
  • ???jsp.display-item.citation.isi??? 64
social impact