title: Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.
abstract: We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain.
authors.affiliation: Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
authors.forename: Luciana Sayuri
authors.initials: LS
authors.lastname: Sanada
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
authors.forename: Karina Laurenti
authors.initials: KL
authors.lastname: Sato
authors.affiliation: Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Nathalia Leilane Berto
authors.initials: NL
authors.lastname: Machado
authors.affiliation: Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Elisabete de Cássia do
authors.initials: Ede C
authors.lastname: Carmo
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
authors.affiliation: Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: vpsfazan@gmail.com.
authors.forename: Valeria Paula Sassoli
authors.initials: VP
authors.lastname: Fazan
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000503:physiopathology*; D002908:Chronic Disease; D005073:Evoked Potentials, Somatosensory; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000503:physiopathology; D008297:Male; D009457:Neuroglia; D017288:Pain Threshold; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar
keywords: Cortex; Development; GFAP; Glial cells; Neonatal pain