title: Morphologic features and glial activation in rat oxaliplatin-dependent neuropathic pain.
abstract: Neurotoxicity is the limiting side effect of the anticancer agent oxaliplatin. A tangled panel of symptoms, sensory loss, paresthesia, dysesthesia, and pain may be disabling for patients and adversely affect their quality of life. To elucidate the morphologic and molecular alterations that occur in the nervous system during neuropathy, rats were daily injected with 2.4 mg kg(-1) oxaliplatin intraperitoneally. A progressive decrease in the pain threshold and hypersensitivity to noxious and nonnoxious stimuli were evidenced during the treatment (7, 14, 21 days). On day 21, morphometric alterations were detectable exclusively in the dorsal root ganglia, whereas the activating transcription factor 3 and neurofilament (heavy-chain) expression changed dramatically in both the nerves and ganglia. Inflammatory features were not highlighted. Interestingly, satellite cells exhibited signs of activation. Glial modulation was characterized in the spinal cord and brain areas involved in pain signaling. On the 21st day, spinal astrocytes increased numerically whereas the microglial population was unaltered. The number of glial cells in the brain differed according to the zone and treatment time points. In particular, on day 21, a significant astrocyte increase was measured in the anterior cingulate cortex, somatosensory area 1, neostriatum, ventrolateral periaqueductal gray, and nucleus raphe magnus.
  
  
  CONCLUSIONS
  These data highlight the relevance of glial cells in chemotherapy-induced neurotoxicity as part of the investigation of the role that specific brain areas play in neuropathy.
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pacini
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaccini
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanardelli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mello
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D003080:Cold Temperature / Q000009:adverse effects; D008297:Male; D009437:Neuralgia / Q000139:chemically induced* / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: ATF3; Chemotherapy-induced neuropathy; astrocytes; microglia; neurofilament; satellite cells