Ontogeny of analgesia elicited by non-nutritive suckling in acute and persistent neonatal rat pain models

Abstract

Significant analgesic and calming effects in human infants and neonatal rodents are produced by orogustatory and orotactile stimuli associated with nursing. These naturally occurring analgesic stimuli may help to protect the vulnerable developing nervous system from the long-term effects of neonatal tissue injury. However, the efficacy of orotactile-induced analgesia across the pre-weaning period, as well as its effects on persistent inflammatory pain, is unknown. Here, we investigated the developmental profile of analgesia produced by orotactile stimulation during non-nutritive suckling in rats. The effects of suckling, as compared to non-suckling littermates, on nocifensive withdrawal responses to thermal and mechanical stimuli were examined at postnatal (P) days P0, P3, P10, P17 and P21. In some rats, Complete Freund's adjuvant (CFA) was injected in a fore- or hindpaw to produce inflammation. For thermal stimuli, suckling significantly increased forepaw withdrawal latencies at P3, P10 and P17, while hindpaw responses were increased at P3 and P10, but not at P17. In inflamed pups, suckling increased fore- and hindpaw response latencies at P10 and P17, but not at P0 or P21. Suckling-induced analgesia was naloxone-insensitive. For mechanical stimuli, suckling-induced analgesia was present at P3, P10 and P17, but not at P21, for both fore- and hindpaws in naı̈ve and inflamed animals. Additionally, suckling had a small but significant effect at P0 for the forepaw in inflamed pups. In nearly all experiments, the peak effect of suckling for thermal and mechanical stimuli occurred at P10. These results indicate that orotactile analgesia, like orogustatory analgesia, is absent or minimal at P0, appears consistently at ∼P3 and is maximal at P10. Unlike gustatory analgesia in rats however, orotactile analgesia persists at least to P17. Orotactile stimulation during suckling effectively reduces transient pain elicited by thermal and mechanical stimuli, as well as persistent hyperalgesia and allodynia caused by inflammation.