Effects of neonatal inflammation on descending modulation from the rostroventromedial medulla

Cutaneous tissue inflammation during the first postnatal week is known to alter long-term development of spinal cord nociceptive circuitry and to alter behavioral responses to noxious stimuli in adult animals. The impact of neonatal inflammation on descending projections arising from supraspinal sites that modulate spinal nociceptive processing is unknown. In the present study, we investigated if altered behavioral responses to pain in adult animals after neonatal inflammation are associated with changes in descending modulation of nocifensive responses elicited from the rostroventromedial medulla (RVM) in lightly anesthetized rats. Compared to handled control animals, hindpaw injection of 0.25% carrageenan (CG) at postnatal day 3 produced adult basal hypoalgesia and increased hyperalgesia 24 h after reinflammation with Complete Freund's Adjuvant (CFA) in awake animals. These effects were specific to the neonatally treated hindpaw, partially replicating previous findings, but were absent in lightly anesthetized animals. However, focal electrical stimulation of the RVM in lightly anesthetized CG treated animals produced significantly greater descending inhibition of nocifensive responses to noxious thermal stimuli applied to the hindpaws and the tail. These effects were partially replicated by intra-RVM microinjection of AMPA. No differences in the efficacy of RVM stimulation between CG and control animals were observed 24 h after reinflammation with CFA. These findings indicate that neonatal tissue injury and inflammation produces lasting alterations in descending modulatory systems that modify nociceptive processing. Taken together with previous studies, these results indicate that changes in pain sensitivity following neonatal tissue injury involve long-term alterations in spinal and supraspinal circuitry.