Acute inflammation induces upregulation of IL-1beta both at the site of the peripheral inflammation and in the cerebrospinal fluid (CSF). The central increase of IL-1beta mainly contributes to the development of hypersensitivity. However, the spinal mechanisms for the effects of IL-1beta in nociceptive transmission are incompletely understood. It is also unknown whether previous sensitization changes IL-1beta activity. We therefore investigated the dose-effect relationship of intrathecal (i.t.) IL-1beta on spinal PGE(2) production in the absence and presence of peripheral formalin inflammation with spinal microdialysis in freely moving rats. The possible involvement of cyclooxygenase (COX) isoforms in the IL-1beta-mediated spinal PGE(2) production on the background of peripheral formalin inflammation was further evaluated with the selective COX-1 and COX-2 inhibitors. We found that the i.t. administration of IL-1beta, with doses of 1, 2, 8, or 16 ng, increased PGE(2) levels in CSF in a dose-related fashion. This IL-1beta-evoked PGE(2) release occurred within 30min after IL-1beta administration, peaked at 30-60 min interval, and returned gradually to the baseline level within 4h. Peripheral formalin inflammation in the paw induced a more prolonged effect of spinal IL-1beta with larger PGE(2) releases in the CSF compared with the non-inflammatory state, suggesting that peripheral inflammation enhances central sensitization. The COX-2 inhibitor SC58236 (15 mg/kg) reduced the IL-1beta-mediated PGE(2) increase in CSF by 86% while the COX-1 inhibitor SC58560 (15 mg/kg) had less effect (28%). Our study suggests that mainly the COX-2 enzyme mediates the IL-1beta-induced increase in spinal PGE(2) in the presence of peripheral formalin inflammation.
This paper deals with a biometric study of 312 boys and girls, aged 2.5-16 years, living in an area with a long history of pollution by lead. The aim was to search for eventual relationships between ten biometric variables and measures of lead absorption in the bodies, i.e. the amount of lead in the blood (PbB), of these children. Standardized values of the biometric variables were compared in the high-PbB and low-PbB categories, by multivariate analysis of variance. Comparison of the vectors of the ten biometric variables reveals a significant difference between the two categories of PbB levels. We found some evidence that the younger children (below 8 years of age) are more likely to absorb lead in the body and are more vulnerable to the effects of subclinical lead intoxication than their older counterparts. The differences between the averages of biometric variables in the two PbB categories are consistently (although not significantly) greater among younger children. This trend disappeared in the older age group. These results confirm data from the literature that young children are especially at risk. It can be concluded that there is a subtle, but significant, influence of lead absorption on the biometric profiles of children and that this effect is probably more important in children below 8 years of age.
Spinal PGE(2) levels are similarly increased after i.t. levobupivacaine injection of 250 and 100 microg. A higher PGE(2) response was observed after a second i.t. injection in the animals receiving 1000 microg lidocaine than those receiving 400 mg lidocaine or either dose of levobupivacaine.
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