The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors’ quality of life. While recent studies have shown that neuroinflammation is involved in PTX-induced peripheral neurotoxicity (PIPN), the pathophysiology of this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated the effects of human intravenous immunoglobulin (IVIg) on a PIPN rat model. PTX-treated rats showed mechanical allodynia and neurophysiological alterations consistent with a severe sensory axonal polyneuropathy. In addition, morphological evaluation showed a reduction of intra-epidermal nerve fiber (IENF) density and evidenced axonopathy with macrophage infiltration, which was more prominent in the distal segment of caudal nerves. Three weeks after the last PTX injection, mechanical allodynia was still present in PTX-treated rats, while the full recovery in the group of animals co-treated with IVIg was observed. At the pathological level, this behavioral result was paralleled by prevention of the reduction in IENF density induced by PTX in IVIg co-treated rats. These results suggest that the immunomodulating effect of IVIg co-treatment can alleviate PIPN neurotoxic manifestations, probably through a partial reduction of neuroinflammation.

Meregalli, C., Monza, L., Chiorazzi, A., Scali, C., Guarnieri, C., Fumagalli, G., et al. (2021). Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(3), 1-14 [10.3390/ijms22031058].

Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity

Meregalli, Cristina
Co-primo
;
Monza, Laura
Co-primo
;
Chiorazzi, Alessia;Fumagalli, Giulia;Alberti, Paola;Pozzi, Eleonora;Canta, Annalisa;Ballarini, Elisa;Rodriguez-Menendez, Virginia;Oggioni, Norberto;Cavaletti, Guido
Penultimo
;
Marmiroli, Paola
Ultimo
2021

Abstract

The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors’ quality of life. While recent studies have shown that neuroinflammation is involved in PTX-induced peripheral neurotoxicity (PIPN), the pathophysiology of this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated the effects of human intravenous immunoglobulin (IVIg) on a PIPN rat model. PTX-treated rats showed mechanical allodynia and neurophysiological alterations consistent with a severe sensory axonal polyneuropathy. In addition, morphological evaluation showed a reduction of intra-epidermal nerve fiber (IENF) density and evidenced axonopathy with macrophage infiltration, which was more prominent in the distal segment of caudal nerves. Three weeks after the last PTX injection, mechanical allodynia was still present in PTX-treated rats, while the full recovery in the group of animals co-treated with IVIg was observed. At the pathological level, this behavioral result was paralleled by prevention of the reduction in IENF density induced by PTX in IVIg co-treated rats. These results suggest that the immunomodulating effect of IVIg co-treatment can alleviate PIPN neurotoxic manifestations, probably through a partial reduction of neuroinflammation.
Articolo in rivista - Articolo scientifico
Axon degeneration; Chemotherapy; IENF; Intravenous immunoglobulin (IVIg); Neuropathic pain; Paclitaxel;
English
2021
1
14
14
Meregalli, C., Monza, L., Chiorazzi, A., Scali, C., Guarnieri, C., Fumagalli, G., et al. (2021). Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(3), 1-14 [10.3390/ijms22031058].
File in questo prodotto:
File Dimensione Formato  
Human Intravenous Immunoglobulin Alleviates Neuropathic.pdf

accesso aperto

Tipologia di allegato: Author’s Accepted Manuscript, AAM (Post-print)
Dimensione 745.14 kB
Formato Adobe PDF
745.14 kB Adobe PDF Visualizza/Apri

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/10281/300031
Citazioni
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 5
Social impact