title: Nociceptive spinal cord neurons of laminae I-III exhibit oxidative stress damage during diabetic neuropathy which is prevented by early antioxidant treatment with epigallocatechin-gallate (EGCG).
abstract: Spinal cord neurons located in laminae I-III respond to nociceptive stimuli and participate in the transmission of painful information to the brain. In the present study we evaluated if nociceptive laminae I-III neurons are affected by oxidative stress damage in a model of diabetic neuropathic pain (DNP), the streptozotocin-induced diabetic rat (STZ rat). Additionally, we evaluated the effects of a preventive antioxidant treatment with epigallocatechin-gallate (EGCG) in nociceptive neuronal activation and behavioural signs of DNP. Three days after diabetes induction, a treatment protocol of STZ rats with an aqueous solution of EGCG in the drinking water was initiated. Ten weeks after the onset of treatment, the spinal cords were immunoreacted against validated markers of oxidative stress damage (8-hydroxy-2'-deoxyguanosine; 8-OHdG) and of nociceptive neuronal activation (Fos). Mechanical hypersensitivity was assessed before and after EGCG treatment. Untreated STZ rats presented increased levels of 8-OHdG immunoreaction, higher numbers of Fos-immunoreacted neurons and high levels of co-localization of 8-OHdG and Fos in laminae I-III. Treatment with EGCG normalized the increase of the above mentioned parameters and ameliorated mechanical hypersensitivity. The present study shows that nociceptive neurons in spinal cord laminae I-III exhibit oxidative stress damage during diabetic neuropathy, which probably affects ascending pain transmission during DNP. The neurobiological mechanisms and translational perspectives of the beneficial effects of a preventive and sustained EGCG treatment in DNP need to be evaluated in the future.
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Portugal; IBMC, University of Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Raposo
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Portugal; IBMC, University of Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Morgado
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Portugal; IBMC, University of Porto, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Pereira-Terra
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Portugal; IBMC, University of Porto, Portugal. Electronic address: isatav@med.up.pt.
authors.forename: I
authors.initials: I
authors.lastname: Tavares
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D014110:Touch
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; C045651:epigallocatechin gallate; D003849:Deoxyguanosine
keywords: Allodynia; Diabetes; Diabetic neuropathic pain; Hyperalgesia; Oxidative stress