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E Kraus

Publications and source records attributed to E Kraus.

At least 73 records · Page 4Linked to original sources

The effect of systemic morphine upon diffuse noxious inhibitory controls (DNIC) in the rat: evidence for a lifting of certain descending inhibitory controls of dorsal horn convergent neurones.

The effects of exogenous opiates upon diffuse noxious inhibitory controls (DNIC) was investigated in intact anaesthetized rats. 58 convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields, were recorded at the lumbar level. These cells received A- and C-peripheral fibre inputs as shown by electrical stimulation of their receptive fields and were mainly located in the medial part of the dorsal horn. The immersion of the distal two-thirds of the tail in hot water (52 degrees C) induced strong inhibition of the responses to both A-(23%) and C-(69%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus. While systemic injection of morphine at a low dose-range (0.1-1 mg/kg) did not significantly affect the unconditioned responses, the DNIC-mediated inhibitions were profoundly altered. (a) DNIC of responses to C fibres were dose-dependently (P less than 0.01) lifted by morphine: (b) the post-effects observed after cessation of conditioning stimuli were dose-dependently (P less than 0.01) diminished; (c) DNIC of responses to A-fibre were similarly altered but this effect was less significant (P less than 0.05); (d) DNIC of responses to sustained moderate pressure were greatly diminished by morphine (P less than 0.01); and (e) these effects were specific since they were antagonized by the opiate antagonist, naloxone. In addition, they were shown to be stereospecific since while the dextrogyre stereoisomer, dextrorphan, was ineffective the levogyre derivative, levorphanol, induced a significant lifting of DNIC. It is concluded that morphine decreases the supraspinal inhibitory controls of dorsal horn convergent neurones, at least when these controls are triggered by noxious stimuli. Assuming that a basic somatosensory background activity (noise) is transmitted to higher centres by dorsal horn convergent neurones, and that the pain-signalling message is the contrast between the activity of the segmental pool of neurones induced by the noxious stimulus and the DNIC-mediated silence of the remaining neuronal population, it is proposed that, by a reduction in DNIC, low-dose morphine could restore the initial level of background activity, the final result being analgesia.

Animals↗

Effect of naloxone upon diffuse noxious inhibitory controls (DNIC) in the rat.

Twenty-eight convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields were recorded at the lumbar level in anaesthetized intact rats. These cells received Aa and C fibre inputs as shown by electrical stimulation of their receptive fields, and were located in the medial part of the dorsal horn. (a) For 15 units, Diffuse Noxious Inhibitory Controls (DNCI)67,68 were investigated by applying noxious thermal stimuli (52 degrees C) to the distal two-thirds of the tail. This conditioning stimulus induced strong inhibition of the responses to both Aa (28%) and C (71%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus. The systemic injection of naloxone (0.3 mg/kg, i.v.) resulted in a partial reduction in these inhibitory effects with a decrease of about 50% for both Aa and C fibre response 10 min after naloxone administration. This was followed by a progressive recovery lasting 30 min. (b) 28 convergent units, including the 15 reported above, were recorded to investigate the effect of naloxone upon the unconditioned response. Responses to Aa fibre were unaffected, whereas the responses to C fibre were slightly (17%) but significantly increased by naloxone.

Afferent Pathways↗

[Are bulbo-spinal serotonergic systems involved in the detection of nociceptive messages? (author's transl)].

Intensely noxious peripheral stimuli of the anaesthetized rat produce two changes in the activity of convergent dorsal horn units: the segmental neuronal pool is activated, while all other convergent neurones are inhibited. These Diffuse Noxious Inhibitory Controls (DNIC) are highly potent (60-80% inhibition) and suppress all convergent neuronal activity, whether spontaneous or evoked by noxious or nonnoxious stimuli. On the other hand, they have no effect on other dorsal horn cell types, including noxious-only and proprioceptive units. The "DNIC" circuits include at least one supraspinal relay since DNIC is not seen in spinal animals. Furthermore, they are greatly reduced by lesions of the Nucleus Raphé Magnus (NRM). It has been shown that this nucleus massively projects onto the spinal cord, in particular onto the dorsal horn, and that stimulation of the NRM results in convergent unit inhibition of the same degree of magnitude as with DNIC. The role of serotonergic mechanisms in DNIC can be demonstrated pharmacologically: pCPA pre-treatment (3 daily I.P. injections, 300 mg/kg) or cinanserin (4 mg/kg I.V.) both result in a potent decrease (50-80%). We have proposed that the nociceptive message from the convergent units could result in a contrast between activity of the activated segmental pool and silence of the remaining convergent units. If this hypothesis can be verified, then some raphé nuclei and brain stem serotonergic pathways may function as filters in the detection of nociceptive messages, allowing extraction of information from somatic background activity including the firing from peripheral mechanoreceptors. While superficially paradoxical in fact our hypothesis fits well with the observation of profound analgesia following NRM stimulation: indeed, this hypothetical contrast would be completely eliminated by NRM stimulation since both neuronal pools would then be inhibited.

Animals↗

[Depression by morphine of various descending inhibitory controls modulating the transmission of nociceptive information at the spinal level in the rat].

Recording from convergent neurones--i. e. those responding to both non-noxious and noxious cutaneous stimuli--in the dorsal horn of the intact anaesthetized Rat, two distinct effects are seen after application of noxious stimuli: there is an activation of units of the segmental pool, along with a very powerful inhibition of the remaining neuronal population (diffuse noxious inhibitory controls, DNIC). Morphine at doses inadequate to directly depress the activity of these units specifically blocks the inhibition. Since DNIC is dependent upon supraspinal mechanisms, these observations show that morphine is capable of depressing certain descending inhibitory controls, at least when these are induced by noxious peripheral stimuli.

Animals↗

Proteinase K from the mold Tritirachium album Limber. Specificity and mode of action.

1) The specificity of proteinase K towards amino acid and oligopeptide nitroanilide substrates is investigated. 2) The active center of the enzyme contains an extended binding region consisting of several subsites. An integral part of the S1-subsite are hydrophobic areas which were investigated by systematic elongation of the carbon skeleton in carboxylic acid 4-nitrophenyl esters. On the basis of these studies, a possible model of the S1-binding site is proposed. 3) Kinetic parameters for the hydrolysis of substituted phenyl acetates catalyzed by proteinase K have been measured at pH 7 and 25 degrees C. Deacylation of an acyl-enzyme intermediate is probably the rate-limiting step. Acylation (kcat/km used as a measure) is modestly sensitive to the sigma values of the substituents (p = 1.33, r = 0.9108), indicating electrophilic assistance by the enzyme in the catalytic mechanism. 4) Hydrophobic forces apparently are not involved in the binding of the leaving group.

Anilides↗