[Prefrontal cortex mediated control of expectations in placebo analgesia]. / Präfrontale Kontrolle von Erwartungen bei der Placebo-Analgesie.

Expectations and beliefs modulate the experience of pain, which is particularly evident in placebo analgesia. The dorsolateral prefrontal cortex (DLPFC) has been associated with pain regulation and with the generation, maintenance and manipulation of cognitive representations. In a heat-pain paradigm, we employed non-invasive low-frequency repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt left and right DLPFC function or used the TMS device itself as a placebo, before applying an expectation-induced placebo analgesia. The results demonstrated that placebo significantly increased pain threshold and pain tolerance. While rTMS did not affect pain experience, it completely blocked placebo analgesia. These findings suggest that expectation-induced placebo analgesia is mediated by symmetric prefrontal cortex function. Possible implications for medical practice and clinical trial research will be discussed in the article.

Two genes encoding a putative multidrug efflux pump of the RND/MFP family are cotranscribed with an rpoH gene in Bradyrhizobium japonicum.

The rpoH3 gene of Bradyrhizobium japonicum codes for one of three sigma32-type transcription factors in this organism and is flanked by rag (rpoH3-associated) genes comprising the chromosomal arrangement ragABrpoH3ragCD. The first genes in this cluster code for a classical two-component regulatory system with an unknown function (Narberhaus et al., 1997. Mol. Microbiol. 24, 93-104). The deduced proteins of the last two genes display a high sequence similarity to heavy metal or multidrug efflux pumps of the RND (Resistance/Nodulation/cell Division)-MFP (Membrane Fusion Protein) family. Reverse transcription and polymerase chain reaction (RT-PCR) analysis demonstrated that ragC is cotranscribed with rpoH3. Mutant strains carrying disrupted rag genes or an extented deletion of the rag locus exhibited neither an apparent growth defect nor a deficiency in the symbiotic interaction with soybean roots. The minimal inhibitory concentrations (MICs) of various metals and organic compounds were identical for the wild-type and mutant strains. Moreover, translational lacZ fusions to each of the first four genes of the rag cluster showed a very low expression under all conditions tested; hence, the substrate for the putative efflux pump has not been uncovered.

Three disparately regulated genes for sigma 32-like transcription factors in Bradyrhizobium japonicum.

Bradyrhizobium japonicum possesses a subclass of heat-shock genes whose members are transcribed from a sigma 32 consensus promoter. Having identified previously one gene (rpoH1) encoding a sigma 32-like RNA polymerase transcription factor, we report here the characterization of two additional rpoH-like genes (rpoH2 and rpoH3). B. japonicum thus represents the first example of an organism possessing an rpoH multigene family. All three rpoH genes encode functional proteins that are able to initiate transcription from the Escherichia coli groE promoter. Each rpoH gene is apparently regulated by a different mechanism. Although both rpoH1 and rpoH2 are transcribed from sigma 70-type promoters, transcription of the rpoH1 operon was found to be heat inducible by an unknown mechanism, whereas the level of rpoH2 mRNA decreased after heat shock. At extreme temperatures (48 degrees C), rpoH2 was transcribed from a second promoter that resembled the E. coli sigma E-type promoter. The rpoH3 gene was found to be associated with two upstream genes, ragA and ragB, coding for a classical two-component regulatory system. Transcription initiated from a promoter that mapped in front of the putative response regulator gene ragA, suggesting that ragA, ragB and rpoH3 are organized in an operon. The ragA promoter was similar to a sigma 32 consensus promoter. The three B. japonicum rpoH genes also varied in their significance to support growth of the organism. While the rpoH2 gene could not be eliminated by mutation, knock-out mutants of rpoH1 and/ or rpoH3 were readily obtained and shown to be indistinguishable from the wild type under aerobic growth conditions or during root-nodule symbiosis. We conclude that rpoH2 is essential for the synthesis of cellular proteins under physiological growth conditions, whereas rpoH1, and probably also rpoH3, are involved in their synthesis during the stress response.