title: Inflammatory pain and hypersensitivity are selectively reversed by epidural bupivacaine and are developmentally regulated.
abstract: BACKGROUND
  Low doses of local anesthetics applied to the young rat spinal cord in vitro have been shown to inhibit C-fiber-evoked responses. The aim of this work was to investigate whether such low doses applied epidurally selectively reduce nociceptive responses in vivo and to investigate the influence of postnatal development on such local anesthetic actions.
  
  
  METHODS
  Three groups of rat pups aged 3, 10, and 21 days were studied. The threshold of the flexion withdrawal reflex to mechanical stimulation was determined in the hind limb at each age. Inflammatory pain was induced in the right hind limb with 2% carrageenan, causing a reduction in the sensory threshold on that side. The difference in threshold between the two sides represents inflammatory hypersensitivity. The effect of low-dose epidural bupivacaine on sensory thresholds and thus the induced hypersensitivity was also determined for each age group.
  
  
  RESULTS
  Inflammatory hypersensitivity was selectively attenuated by very low doses of bupivacaine (concentration range. 0.004-0.0625%), which did not affect the sensory threshold in the contralateral uninflamed limb. This effect was also age-related, with younger rats being more sensitive than older rats.
  
  
  CONCLUSIONS
  The effects of epidural bupivacaine in the infant rat are developmentally regulated. Lower doses have a selective analgesic effect that decreases with increasing postnatal age.
authors.affiliation: Department of Anesthesia, Great Ormond Street Hospital for Children NHS Trust and the Institute of Child Health, London, United Kingdom. r.howard@ich.ucl.ac.uk
authors.forename: R F
authors.initials: RF
authors.lastname: Howard
authors.forename: D J
authors.initials: DJ
authors.lastname: Hatch
authors.forename: T J
authors.initials: TJ
authors.lastname: Cole
authors.forename: M
authors.initials: M
authors.lastname: Fitzgerald
mesh_terms: D000375:Aging / Q000502:physiology; D015360:Analgesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000627:therapeutic use*; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000779:Anesthetics, Local; D002351:Carrageenan; D002045:Bupivacaine