TY - JOUR
T1 - Intravenous neural stem cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy
AU - Franchi, Silvia
AU - Valsecchi, Anna E.
AU - Borsani, Elisa
AU - Procacci, Patrizia
AU - Ferrari, Daniela
AU - Zaffa, Cristina
AU - Sartori, Patrizia
AU - Rodella, Luigi F.
AU - Vescovi, Angelo
AU - Maione, Sabatino
AU - Rossi, Francesco
AU - Sacerdote, Paola
AU - Colleoni, Mariapia
AU - Panerai, Alberto E.
N1 - Funding Information:
This work was supported by Grants from the Italian Ministry of Education University and Scientific Research to A.E.P. and L.F.R. (PRIN 2007, 20077R93XF).
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Cytokines
KW - Nerve repair
KW - Neuropathic pain
KW - Stem cells
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U2 - 10.1016/j.pain.2012.01.008
DO - 10.1016/j.pain.2012.01.008
M3 - Article
C2 - 22321918
AN - SCOPUS:84858709161
SN - 0304-3959
VL - 153
SP - 850
EP - 861
JO - Pain
JF - Pain
IS - 4
ER -