Neonatal immune challenge alters nociception in the adult rat

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Abstract
Accharide (LPS), an established model of immune system activation, has been shown to affect febrile and cyclooxygenase-2 (COX-2) responses to a similar exposure in adulthood. Adult LPS also elicits a range of sickness behaviours, including enhanced responses to painful stimuli. We, therefore, hypothesized that adult sensation and pain responses could be affected by a neonatal LPS challenge. Male and female Sprague–Dawley rats were administered LPS at postnatal day 14 and were tested in adulthood for nociceptive responses to thermal and mechanical stimuli using, respectively, a plantar test apparatus and von Frey filaments, before and after adult LPS. Expression of dorsal root ganglion and lumbar spinal cord COX-2 was also examined. Animals treated as neonates with saline showed the expected hypersensitivity to painful stimuli after adult LPS as well as enhanced spinal cord COX-2. Neonatally LPS-treated rats, however, showed a significantly different profile. They displayed enhanced baseline nociception and elevated basal spinal cord COX-2 compared with neonatally saline-treated rats. Also, rather than the expected hyperalgesia after adult LPS, no changes in nociceptive responses and a reduction in spinal cord COX-2 expression were observed. These findings have important implications for the understanding of pain and its management and highlight the importance of the neonatal period in the development of pain pathways....