Neonatal chronic hind paw inflammation alters sensitization to intradermal capsaicin in adult rats: a behavioral and immunocytochemical study.J Pain. 2005 Dec; 6(12):798-808.JP
The present studies were conducted to examine functional consequences of postnatal chronic inflammation, initiated during a critical developmental period, on capsaicin-evoked hyperalgesia and neuronal activation in adulthood. Rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA; diluted 2:1 in saline) on postnatal day 0 (P0-CFA) or 14 (P14-CFA). Separate groups received an equivalent volume of saline on P0 (P0-vehicle) or were untreated (P0-untreated). Increases in capsaicin-evoked thermal and mechanical hyperalgesia and allodynia were observed in adult P0-CFA-treated rats relative to control conditions. By contrast, this enhancement was absent in P14-CFA-treated rats, suggesting that the developmental period differentially affects the appearance of the observed behavioral phenotype. Capsaicin-evoked nocifensive behavior was also lower in P14-CFA-treated rats relative to P0-CFA-treated rats. Capsaicin-evoked Fos protein expression was increased in the superficial and neck regions of the dorsal horn of adult P0-CFA-treated rats relative to P0-vehicle-treated rats. These changes were absent in the nucleus proprius and ventral horn. The present data are consistent with the hypothesis that neonatal chronic inflammation permanently alters sensitivity to pain in adulthood, consistent with modulation of primary afferent activation and central sensitization in response to a subsequent nociceptive challenge in adulthood.
Chronic inflammation during development can induce profound alterations in sensory processing later in life. Here we show that long-term inflammation initiated at critical developmental stages sensitizes both behavioral and neuronal responses to nociceptor stimulation in adulthood. An ongoing sensitization of the spinal cord is induced by the postnatal inflammatory insult.