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Perinatal progesterone decreases the hyperalgesic response to surgery in the adult: a study on female rats
Abstract Number: BP-05
Abstract Type: Original Research
Background: There recently has been a substantial increase in survival of preterm infants and an increase of in utero fetal surgeries. Noxious stimulation in the newborn alters the pain response to injury in adult life. Progesterone, an effective antihyperalgesic agent in the adult is in high concentration in the pregnant mother and preterm infants are prematurely withdrawn from this high progesterone environment. Therefore, we investigated the effects of early life progesterone on later life pain perception.
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 hind paw at P3, the other half not. At P60 all groups of these now adult rats received a second incision. Tactile sensitivity, measured by thresholds to von Frey hair stimulation, and thermal sensitivity, measured by withdrawal latencies from a radiant heat source, were measured weekly at P14-P42 (Period I), at P60 (just before an incision), and every 2 days of P61- P70 (Period II). At P60 rats were fixed by systemic paraformaldehyde perfusion and spinal cords taken for staining and immunohistochemical analysis of activated p-p38 MAP kinases.
Results: Rats that were incised at P3 had greater tactile and thermal hyperalgesia in Period I than the non-operated rats, a difference that was abolished by progesterone treatment. P3 incision also resulted in longer lasting tactile and thermal hyperalgesia after the P60 incision (Period II), all of which were markedly smaller in degree and faster to resolve in rats receiving early progesterone. Remarkably, even in rats that were not operated 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.
Conclusion: Progesterone treatment of the early neonate not only diminishes the adult post-operative sensitization that is caused by early neonatal injury, but also lessens the degree of acute post- operative hyperalgesia in the intact adult. This suggests that endogenously high progesterone in utero may have a similarly protective action, and, furthermore, that development of nociceptive circuitry can be strongly influenced by neonatal progesterone.