The distinction between glial painful and protective pathways is unclear and the possibility to finely modulate the system is lacking. Focusing on painful neuropathies, we studied the role of interleukin 1 alpha (IL-1 alpha), an alarmin belonging to the larger family of damage-associated molecular patterns endogenously secreted to restore homeostasis.The treatment of rat primary neurons with increasing doses of the neurotoxic anticancer drug oxaliplatin (0.3-100 mu M, 48 h) induced the release of IL-1 alpha. The knockdown of the alarmin in neurons leads to their higher mortality when co-cultured with astrocytes. This toxicity was related to increased extracellular ATP and decreased release of transforming growth factor beta 1, mostly produced by astrocytes.In a rat model of neuropathy induced by oxaliplatin, the intrathecal treatment with IL-1 alpha was able to reduce mechanical and thermal hypersensitivity both after acute injection (100 ng and 300 ng) and continuous infusion (100 and 300 ng/die(-1)). Ex vivo analysis on spinal purified astrocyte processes (gliosomes) and nerve terminals (synaptosomes) revealed the property of IL-1 alpha to reduce the endogenous glutamate release induced by oxaliplatin. This protective effect paralleled with an increased number of GFAP-positive cells in the spinal cord, suggesting the ability of IL-1 alpha to evoke a positive, conservative astrocyte phenotype.Endogenous IL-1 alpha induced protective signals in the cross-talk between neurons and astrocytes. Exogenously administered in rats, IL-1 alpha prevented neuropathic pain in the presence of spinal glutamate decrease and astrocyte activation.

Neuronal alarmin IL-1α evokes astrocyte-mediated protective signals: Effectiveness in chemotherapy-induced neuropathic pain / Di Cesare Mannelli, Lorenzo; Micheli, Laura; Cervetto, Chiara; Toti, Alessandra; Lucarini, Elena; Parisio, Carmen; Marcoli, Manuela; Ghelardini, Carla. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - ELETTRONICO. - 168:(2022), pp. 105716-105716. [10.1016/j.nbd.2022.105716]

Neuronal alarmin IL-1α evokes astrocyte-mediated protective signals: Effectiveness in chemotherapy-induced neuropathic pain

Di Cesare Mannelli, Lorenzo;Micheli, Laura;Toti, Alessandra
;
Lucarini, Elena;Parisio, Carmen;Ghelardini, Carla
2022

Abstract

The distinction between glial painful and protective pathways is unclear and the possibility to finely modulate the system is lacking. Focusing on painful neuropathies, we studied the role of interleukin 1 alpha (IL-1 alpha), an alarmin belonging to the larger family of damage-associated molecular patterns endogenously secreted to restore homeostasis.The treatment of rat primary neurons with increasing doses of the neurotoxic anticancer drug oxaliplatin (0.3-100 mu M, 48 h) induced the release of IL-1 alpha. The knockdown of the alarmin in neurons leads to their higher mortality when co-cultured with astrocytes. This toxicity was related to increased extracellular ATP and decreased release of transforming growth factor beta 1, mostly produced by astrocytes.In a rat model of neuropathy induced by oxaliplatin, the intrathecal treatment with IL-1 alpha was able to reduce mechanical and thermal hypersensitivity both after acute injection (100 ng and 300 ng) and continuous infusion (100 and 300 ng/die(-1)). Ex vivo analysis on spinal purified astrocyte processes (gliosomes) and nerve terminals (synaptosomes) revealed the property of IL-1 alpha to reduce the endogenous glutamate release induced by oxaliplatin. This protective effect paralleled with an increased number of GFAP-positive cells in the spinal cord, suggesting the ability of IL-1 alpha to evoke a positive, conservative astrocyte phenotype.Endogenous IL-1 alpha induced protective signals in the cross-talk between neurons and astrocytes. Exogenously administered in rats, IL-1 alpha prevented neuropathic pain in the presence of spinal glutamate decrease and astrocyte activation.
2022
168
105716
105716
Di Cesare Mannelli, Lorenzo; Micheli, Laura; Cervetto, Chiara; Toti, Alessandra; Lucarini, Elena; Parisio, Carmen; Marcoli, Manuela; Ghelardini, Carla
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0969996122001085-main.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 3.4 MB
Formato Adobe PDF
3.4 MB Adobe PDF Visualizza/Apri

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

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1295999
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 2
social impact