title: Age-dependent sensitization of cutaneous nociceptors during developmental inflammation.
abstract: BACKGROUND
  It is well-documented that neonates can experience pain after injury. However, the contribution of individual populations of sensory neurons to neonatal pain is not clearly understood. Here we characterized the functional response properties and neurochemical phenotypes of single primary afferents after injection of carrageenan into the hairy hindpaw skin using a neonatal ex vivo recording preparation.
  
  
  RESULTS
  During normal development, we found that individual afferent response properties are generally unaltered. However, at the time period in which some sensory neurons switch their neurotrophic factor responsiveness, we observe a functional switch in slowly conducting, broad spiking fibers ("C"-fiber nociceptors) from mechanically sensitive and thermally insensitive (CM) to polymodal (CPM). Cutaneous inflammation induced prior to this switch (postnatal day 7) specifically altered mechanical and heat responsiveness, and heat thresholds in fast conducting, broad spiking ("A"-fiber) afferents. Furthermore, hairy skin inflammation at P7 transiently delayed the functional shift from CM to CPM. Conversely, induction of cutaneous inflammation after the functional switch (at P14) caused an increase in mechanical and thermal responsiveness exclusively in the CM and CPM neurons. Immunocytochemical analysis showed that inflammation at either time point induced TRPV1 expression in normally non-TRPV1 expressing CPMs. Realtime PCR and western blotting analyses revealed that specific receptors/channels involved in sensory transduction were differentially altered in the DRGs depending on whether inflammation was induced prior to or after the functional changes in afferent prevalence.
  
  
  CONCLUSIONS
  These data suggest that the mechanisms of neonatal pain development may be generated by different afferent subtypes and receptors/channels in an age-related manner.
authors.affiliation: Department of Anesthesia, Division of Pain Management, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 6016, Cincinnati, OH 45229, USA. michael.jankowski@cchmc.org.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jankowski
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Ross
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Weber
authors.forename: Frank B
authors.initials: FB
authors.lastname: Lee
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Shank
authors.forename: Renita C
authors.initials: RC
authors.lastname: Hudgins
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000367:Age Factors; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D058477:Receptors, Purinergic P2X3 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000294:innervation / Q000473:pathology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D006023:Glycoproteins; D058477:Receptors, Purinergic P2X3; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C473590:isolectin B4-binding glycoprotein, mouse; D002351:Carrageenan