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Quantitative thermal and mechanical algometry was studied in 4 human subjects exposed to various concentrations of capsaicin administered topically to the skin of the palm or forearm. Treated skin patches were assessed for changes in heat pain threshold and in mechanical pain threshold at various controlled temperatures. The results showed that: (1) in addition to heat hyperalgesia, capsaicin consistently induces overt mechanical hyperalgesia; (2) thermal and mechanical hyperalgesias are linearly dependent on the log of capsaicin dose; (3) mechanical hyperalgesia is increased by increasing skin temperature; (4) mechanical hyperalgesia is abolished by cooling the skin to a point about 10 degrees C below the threshold for heat pain, a temperature that does not impair touch or sharp pain sensation. These sensory effects of capsaicin are mediated by C fibres, since dissociated A fibre block established by compression-ischaemia does not abolish either spontaneous pain or mechanical hyperalgesia. In addition, abolition of mechanical hyperalgesia by cooling persists during A fibre block. Cooling thus appears to act directly, presumably decreasing hyperexcitability of the C nociceptor. Hyperalgesia is also transiently depressed for at least 30 min during the postischaemic period, well beyond the duration of paraesthesiae or overt hyperaemia. Sensory changes identical to those induced experimentally by capsaicin have been observed in patients with a particular variety of neuropathic pain (ABC syndrome) and have been termed polymodal hyperalgesia and cross modality threshold modulation (Ochoa, 1986; Ochoa et al., 1987). Based on these overall observations, it is postulated here that the sensory abnormalities induced by capsaicin and those observed in this particular variety of patients relate to primary hyperalgesia and share a common mechanism in that the excitable receptor membrane of polymodal C nociceptors behaves as if it 'misreads' temperature.

Edeine, a small basic peptide antibiotic, is shown to inhibit initiation of polyphenylalanine and globin peptides with little or no effect on peptide extension in cell-free systems derived from rabbit reticulocytes. Approximately a 1 to 1 molar ratio of edeine to ribosomes is sufficient for maximum inhibition of synthesis. In a poly(U)-directed system the antibiotic inhibits deacylated tRNAPhe binding into the donor ribosomal site and enzymatic or nonenzymatic binding of phenylalanyltRNA into the acceptor site. Resistance to edeine inhibition of polyphenylalanine synthesis or phenylalanyl-tRNA binding is produced by preliminary incubation of deacylated tRNA, poly(U), and ribosomes to form an initiation complex with deacylated tRNAPhe bound into the donor ribosomal site. Edeine blocks binding of phenylalanyl-tRNA or methionyl-tRNA to the smaller ribosomal subunit ; however, it has a surprising stimulatory effect on methionyl-tRNA binding or methionylpuromycin formation with recombined ribosomal subunits.Globin synthesis in vitro on ribosomes isolated from whole cells previously incubated with NaF is partially inhibited by a high concentration of edeine while NaF completely inhibits synthesis. These "Nal? ribosomes" carry tRNAfMet apparently in the form of an initiation complex accumulated during inhibition nf peptide initiation by NaF. Edeine appears to inhibit peptide initiation a t a point prior to the reaction inhibited by NaF. It is suggested that edeine inhibits peptide initiation by blocking a critical site on the 40 S ribosomal subunits, thus preventing functional integration of endogenous mRNA or Met-tRNAfMet into an initiation complex.Edeine is a broad spectrum antibiotic which inhibits growth of yeasts, molds and both gram negative and gram positive bacteria, as well as mycoplasma [I]. It has been shown to be a mixture of Using an ribosomal system derived from E. coli in vitro, Hierowski and Kurylo-Borowska observed that edeine a t concentrations as low as 0.1 pM inhibited poly(U) directed binding of Phe-tRNA to ribosomes and the synthesis of polyphenylalanine [5]. No inhibitory effect on polyphenylalanine synthesis was observed if a ternary complex of ribosomes, poly(U) and Phe-tRNA was formed prior to the addition of edeine to the reaction mixture. Edeine appeared to have much less inhibitory effect on peptide synthesis directed by f2 phage RNA or endogenous Unusual Abbreviations. T I and TII, the nomenclature for transfer enzymes suggested by Siler and Moldave [30]; TI is the reticulocyte binding enzyme or transfer factor I, TI1 is transfer factor 11. Abbreviation for nucleic acids follow CBN rules, see Eur. J . Biochem. 15 (1970) 203. AZq0 unit, the amount of material in 1 ml of solution which gives an absorbance of 1 in a 1 cm light path at 260 nm. mRNA than on peptide synthesis directed by synthetic polynucleotides in the system derived from E. coli in vitro. No inhibition of poly(U) binding to ribosomes was observed. Other studies indicated that edeine causes association of 30 S and 50 S E . col...