Inflammation-induced hyperalgesia and spinal microglia reactivity in neonatal rats

Abstract

Background: Peripheral inflammation and nerve injury evoke pain behaviours in adult rodents mediated by sensitization, a process that involves the activation of microglia in the spinal cord. In neonates, however, peripheral inflammation, but not nerve injury, induces a lasting hyperalgesia. It is known that microglia does not activate after nerve injury in young pups; however, changes in microglia associated with inflammation in neonatal animals have not been studied. Methods: Inflammation was induced by unilateral intraplantar injection of carrageenan, complete Freund’s adjuvant or zymosan in 10-day-old rats. Rats were tested for mechanical sensitivity in response to punctuate stimulation of the dorsal surface of the hind paw using calibrated von Frey filaments. Immunohistochemistry was used to detect changes in size and density of microglial cells using the specific marker Iba-1. The effects of minocycline applications (120 mg, i.t.) on spinal microglia and behaviour induced by zymosan inflammation were studied. Results: Hind paw inflammation in young P10 rats, with either of the agents used, produced an immediate hyperalgesia, which lasted more than 7 days. A concomitant and significant increase in cell size and density in Iba-1-positive cells was observed in the spinal dorsal horn. These morphological changes in spinal microglia were observed as early as 1-h post-inflammation. Intrathecal and systemic administration of minocycline blocked the hyperalgesia and the changes in spinal microglia produced by zymosan. Conclusions: Results suggest a key role for spinal microglia activation in the development of hyperalgesia following inflammation in neonatal animals.