title: Systemic Progesterone Administration in Early Life Alters the Hyperalgesic Responses to Surgery in the Adult: A Study on Female Rats.
abstract: BACKGROUND
  There has recently been a substantial increase in the survival of prematurely born neonates and an increase of in utero surgeries. Noxious stimulation in the newborn alters the pain response to injury in adult life. Progesterone, an effective antihyperalgesic agent in the adult, is at high concentration in the pregnant mother. Therefore, we investigated the effects of early-life progesterone on postsurgical outcomes in adult rats.
  
  
  METHODS
  Female rat pups were administered progesterone or vehicle during the first 7 days postpartum (P1-P7). A second control group had no injections. Half of each of these groups received an incision of the hindpaw at P3 and the other half did not. At P60, all groups of these now adult rats received a second paw incision. Tactile sensitivity and thermal sensitivity were measured weekly at P14-P42 (period I), at P60 (just before the second incision), and every 2 days of P61-P70 (period II). At P67, rats were fixed by systemic paraformaldehyde perfusion and their spinal cords taken for staining and immunocytochemical analysis of activated p-p38 mitogen-activated protein kinase.
  
  
  RESULTS
  Rats with surgery at P3 had greater tactile and thermal hyperalgesia in period I than the nonoperated rats, a difference abolished by progesterone treatment. P3 incision also resulted in long-lasting tactile and thermal hyperalgesia after the P60 incision (period II), both of which were markedly smaller in degree and faster to resolve in rats receiving early progesterone. Even in rats that were not operated on in period I, neonatal progesterone lessened the tactile hyperalgesia in period II. More spinal cells showed p-p38 staining in vehicle-treated rats as a result of the early-life incision but not in those treated with progesterone.
  
  
  CONCLUSIONS
  These findings suggest that endogenously high progesterone in utero may have a similarly protective action and that the development of nociceptive circuitry can be strongly influenced by neonatal progesterone.
authors.affiliation: From the *Women's Pain Group and the †Pain Research Center, Brigham & Women's Hospital, Boston, Massachusetts; and ‡Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mieke
authors.initials: M
authors.lastname: Soens
authors.forename: Jeffrey C-F
authors.initials: JC
authors.lastname: Wang
authors.forename: Temugin
authors.initials: T
authors.lastname: Berta
authors.forename: Gary
authors.initials: G
authors.lastname: Strichartz
mesh_terms: D000367:Age Factors; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006930:Hyperalgesia / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D059225:Nociception / Q000187:drug effects; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D010766:Phosphorylation; D011374:Progesterone / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013127:Spinal Nerves / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000700:Analgesics; D011374:Progesterone; D048051:p38 Mitogen-Activated Protein Kinases