Long-term effects of short-lasting early local inflammatory insult

Abstract

We examined the long-term effects of a short-lasting (approximately 24 h) inflammatory insult generated by injections of 0.25% carrageenan (1 microl/g) into the hindpaws of newborn (P0) rat pups. At P60 animals which experienced this early inflammatory insult showed significant alterations in the withdrawal responses to noxious stimulation of the affected paws. Furthermore, in the absence of ongoing inflammation, the withdrawal latencies to heat stimulation and withdrawal thresholds to mechanical stimulation were increased by such experience. In the presence of ongoing CFA-induced inflammation, however, the same early experience decreased these parameters of response to noxious stimulation. These data suggest that early inflammatory insult may differentially affect the aspects of nociceptive circuitry involved in transient pain sensitivity and in inflammation-induced hyperalgesia.

Artificial Rearing of Rat Pups Reveals the Beneficial Effects of Mother Care on Neonatal Inflammation and Adult Sensitivity to Pain

“…Moreover, contrary to our prediction, AR-MAX rats exhibited higher pain sensitivity in adulthood than AR-MIN rats. Repeated neonatal injections, both saline and formalin, did not affect adult pain sensitivity to formalin in this study, which contrasts other studies using different models of early pain (23). However, exposure to neonatal stressors completely eliminated the effects of rearing on adult pain sensitivity although, overall, there was a trend for higher pain sensitivity in the AR groups.…”

Free-Ranging Macaque Mothers Exaggerate Tool-Using Behavior when Observed by Offspring

“…On the other hand, the hyposensitivity seen in a subset of neonatally injured rats is in striking contrast with the Correlation of visceral and somatic sensitivity hypersensitivity seen in a different subset, but consistent with the hyposensitivity reported in other models of neonatal injury [23]. It may be related to a myriad of factors, including 1) desensitization of primary afferents caused by permanent damage during the neonatal period, 2) changes in the sensitization of the pain pathways in the CNS whereby desensitization (similar to long term depression) may have taken effect; or, 3) the triggering of a desensitization response, in what may appear to be an "inoculation" against pain, by neuroimmune factors reported to be involved in the immediate sensitization following injury.…”

“…In adult rats exposed to a brief period of inflammation just after birth, the skin receptive field supplied by individual dorsal horn neurons decreased by more than 30% [22], implying permanent alterations in the spinal pain processing for these areas. Short-lasting local inflammation (produced by injection of 0.25% carageenan), produced a long-term hypoalgesia at baseline, which occurred equally in the previously injured and uninjured paws [23]. However, after re-inflammation, a long-term hyperalgesia occurred in the neonatally-injured paw, indicating a significant segmental involvement in the spinal processing of pain [24].…”

Activity-Dependent Modulation of Glutamatergic Signaling in the Developing Rat Dorsal Horn by Early Tissue Injury

“…Mounting evidence suggests that tissue damage during a critical period of early postnatal development results in a delayed decrease in mechanical and thermal sensitivity in both rats (Chu et al 2007;Lidow et al 2001;Ren et al 2004) and children (Hermann et al 2006;Schmelzle-Lubiecki et al 2007;Walker et al 2009). These prolonged behavioral effects may partly reflect alterations in spinal cord function, given that distinct changes in gene expression are known to occur within the adult dorsal horn following neonatal tissue damage (Ren et al 2005).…”