In the present study, we examined the effects of prostaglandin E 1 (PGE 1 ) on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on peripheral blood mononuclear cells (PBMC) using fluorescenceactivated cell sorting analysis as well as its effects on cytokine production using enzyme-linked immunosorbent assay. Whereas no inhibitor of spontaneous expression of adhesion molecules was reported, we found that PGE 1 inhibited spontaneous ICAM-1, B7.2, and CD40 expression on monocytes in a concentration-dependent manner but had no effect on the expression of B7.1 and CD40L. Although interleukin (IL)-18 induced the expression of ICAM-1, B7.2, CD40, and CD40L, PGE 1 prevented IL-18-induced expression of ICAM-1, B7.2, and CD40. We examined the involvement of five subtypes of PGE 1 receptors (IP, EP1, EP2, EP3, and EP4) in the effect of PGE 1 on the expression of these adhesion molecules using subtype-specific agonists. Among EP receptor agonists, EP2 and EP4 receptor agonists inhibited IL-18-elicited ICAM-1, B7.2, and CD40 expression. ONO-1301 (IP receptor agonist) prevented the expression of ICAM-1, B7.2, and CD40 regardless of the presence of IL-18 with the same potency as PGE 1 . The effect of a combination of ONO-1301 and 11-deoxy (D)-PGE 1 (EP2/EP4 receptor agonist) on ICAM-1, B7.2, and CD40 expression mimicked that of PGE 1 . Moreover, PGE 1 inhibited the production of IL-12 and interferon-␥ in PBMC in the presence and absence of IL-18, whereas PGE 1 induced IL-10 production. In conclusion, IP receptor and EP2/EP4 receptor play an important role in the action of PGE 1 on the expression of adhesion molecules on monocytes and cytokine production.

In 4 patients with a complete upper limb palsy due to traumatic cervical root avulsion, surgical anastomosis of intercostal to musculocutaneous nerves was performed to restore function in the biceps brachii muscle. Four to 6 months after the operation, motor unit discharges were recorded from the biceps muscle on the operated side during deep breathing and by cortical magnetic stimulation. The motor unit discharges became independent from respirations gradually over 1 to 2 years. The latencies of the motor potentials evoked by cortical and thoracic root magnetic stimulation decreased gradually over 2 to 3 years. Motor cortex mapping of the reinnervated biceps muscle showed a gradual change over 4 to 33 months from the area of the intercostal muscles to that of the arm area, which was more lateral on the motor cortex. These findings suggest that reorganization of the motor cortex to arm flexor muscles occurs following peripheral nerve anastomosis.

TNF-α up-regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF-α up-regulated the protein expression of the TTX-S NaV1.7 channel in adrenal chromaffin cells. Our findings may contribute to understanding the peripheral nociceptive mechanism of TNF-α.

Lipopolysaccharide (LPS) is recognized as a key molecule in the pathogenesis of Gram negative sepsis and septic shock. In the present study, we demonstrate that LPS (1-1000 pg/ml) concentration dependently up-regulated the expression of intercellular adhesion molecule (ICAM)-1, B7.1, and B7.2 on human monocytes using fluorescence-activated cell sorting analysis, and that tumor necrosis factor (TNF)-␣ production induced by LPS in peripheral blood mononuclear cells (PBMCs) was inhibited by the addition of antibodies against these adhesion molecules, suggesting the dependence of TNF-␣ production on cell-cell interaction through these adhesion molecules. Moreover, we found that histamine (10 Ϫ7 -10 Ϫ4 M) concentration dependently inhibited the expression of ICAM-1 and B7.1, but not B7.2 on monocytes induced by LPS. Histamine also inhibited the responses of TNF-␣ production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-␣ production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H2-receptor agonists but not by H1-, H3-, and H4-receptor agonists, indicating the involvement of H2-receptors in the histamine action. Dibutyryl cAMP down-regulated ICAM-1 and B7.1 expression on monocytes stimulated by LPS, suggesting the mediation by the cyclic adenosine monophosphate-protein kinase A pathway of H2-receptor activation. These results as a whole indicated that histamine via H2-receptor inhibited the LPS-induced TNF-␣ production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.

Available evidence indicates voltage-gated Na + channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na + currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms.