title: Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.
abstract: Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.
authors.affiliation: Laboratory of Neuroimmunology, School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Ihssane
authors.initials: I
authors.lastname: Zouikr
authors.affiliation: Neurobiology of Addiction Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Morgan H
authors.initials: MH
authors.lastname: James
authors.affiliation: Neurobiology of Addiction Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Campbell
authors.affiliation: Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Clifton
authors.affiliation: Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.affiliation: Neurobiology of Addiction Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Dayas
authors.affiliation: Laboratory of Neuroimmunology, School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Hodgson
mesh_terms: D000698:Analgesia / Q000379:methods; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism* / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde