Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult ratsReport as inadecuate

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Molecular Pain

, 1:27

First Online: 22 September 2005Received: 25 July 2005Accepted: 22 September 2005


Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan CAR injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors to compare gene expression profiles in the lumbar spinal dorsal horn LDH of adult P60 male rats that received neonatal CAR treatment within at postnatal day 3; P3 and outside at postnatal 12; P12 of the sensitive period. The data were obtained both without inflammation at baseline and during complete Freund-s adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems in the LDH ipsilateral to the neonatally-injured paw. The largest aberration in gene expression, however, was observed during inflammation of the neonatally injured hindpaws in the ipsilateral LDH, which included thirty-six genes encoding numerous members of glutamate, serotonin, GABA, calcitonin gene-related peptide, neurotrophin, and interleukin systems. These findings suggest that changes in gene expression may be involved in the long-term nociceptive effects of neonatal noxious insult at the spinal level.

Keywordsmicroarray real-time RT-PCR neonatal injury carrageenan pain development Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-1-27 contains supplementary material, which is available to authorized users.

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Author: Ke Ren - Svetlana I Novikova - Fang He - Ronald Dubner - Michael S Lidow



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