Biomedical subjects

C Forster

Publications and source records attributed to C Forster.

At least 55 records · Page 3Linked to original sources

PubMed1998

An electropalatographic (EPG) study of the speech of two stuttering subjects.

Two stuttering subjects and two control subjects were used in a comparative pilot study using EPG. The subjects read twenty sentences and repeated three words, 'a deer', 'a clock' and 'a kitkat', ten times. These data allowed three main methods of EPG analysis: variability measures on the three words in isolation; qualitative comparison between stuttering and control speakers' production of perceptually fluent speech and analysis of specific disfluencies. Results showed that compared to control speakers the stuttering subjects displayed increased contacts for fluent alveolar and velar plosives and fricative undershoot. They also showed less temporal variability for velar stop articulations. The results suggest that EPG is a useful technique in the analysis of articulatory characteristics of stuttering behaviour.

Adult↗

PubMed1997

Chloroethylclonidine and alpha-adrenoceptor agonist interaction in blood vessels following heart failure.

This study examined the interaction of chloroethylclonidine with alpha-adrenoceptor agonists in canine endothelium-denuded dorsal pedal artery and saphenous vein before (non-paced) and at end-stage heart failure which was induced by rapid ventricular pacing (250 bpm for no more than four weeks). The interaction was heterogeneous in both non-paced and heart failure blood vessels. In the dorsal pedal artery, only chloroethylclonidine (10(-4) M) reduced the maximum response to noradrenaline. At 10(-6) and 10(-5) M, chloroethylclonidine potentiated the response to noradrenaline. In the saphenous vein, chloroethylclonidine was not surmountable against noradrenaline before heart failure, but produced competitive antagonism of noradrenaline in the heart failure group (pA2 = 5.7). In the dorsal pedal artery, chloroethylclonidine potentiated the response to low concentrations of methoxamine, but inhibited the response of higher concentrations. In the saphenous vein, chloroethylclonidine (10(-6) and 10(-5) M) potentiated the response to methoxamine from non-paced dogs but did not significantly effect the response at heart failure. In the dorsal pedal artery, chloroethylclonidine (10(-4) M) potentiated low concentrations and inhibited higher concentrations of phenylephrine from non-paced animals but had no significant effect at heart failure. In contrast, in the saphenous vein, chloroethylclonidine (at all concentrations tested) inhibited the response to phenylephrine in non-paced dogs, whereas the inhibitory effect was not as marked in heart failure. In conclusion, these results indicate that differences in alpha1-adrenoceptor populations and distribution are blood vessel dependent and dependent on the pathological state.

Adrenergic alpha-Agonists↗

PubMed1997

Flare responses of atopic eczema patients analysed with true colour images.

OBJECTIVE AND DESIGN: Attenuated flare responses of atopic eczema (AE) patients to histamine are well documented, but their origin is still unknown. SUBJECTS AND METHODS: Here we studied the development of erythema after histamine iontophoresis in 12 AE patients and 12 healthy volunteers by means of a RGB-camera for recording true colour images. TREATMENT: 10 mg cetirizine or placebo was administered orally 3 h before the experiment in a crossover design. RESULTS: The flare reaction was found to develop after termination of histamine iontophoresis in two phases: a first phase lasting 1-2 min in which the flare increased by about 10 mm2/s and a second phase lasting another 10-15 min characterized by a slower growth in the range of 1 mm2/s. CONCLUSIONS: Flare size was diminished in AE patients, mainly due to a slower or absent growth in the second phase. Oral application of the H1-antagonist cetirizine (Zyrtec) reduced the flare reaction in both groups of volunteers significantly, indicating that the reaction is dependent on the activation of chemosensitive nerve fibres via H1-receptors.

Adult↗

PubMed1997

Angiotensin-(1-7) and the rat aorta: modulation by the endothelium.

Peptide metabolites of angiotensin I and II are active components of the renin-angiotensin system. One such peptide is angiotensin-(1-7), which has been shown to be present in various tissues and has properties distinct from those of angiotensin II. We examined the effects of angiotensin-(1-7) on endothelium-intact and denuded rat aorta. Second, we evaluated whether an interaction occurred between angiotensin-(1-7) and angiotensin peptides, as well as noradrenaline. Finally, we addressed whether the responses to angiotensin-(1-7) were mediated by an AT1 receptor. Angiotensin-(1-7) produced concentration-dependent relaxations of the rat aorta that were significantly greater in endothelium-intact preparations (81.1 +/- 18.9% and 29.6 +/- 2.9% for intact and denuded, respectively). Angiotensin-(1-7) inhibited responses generated to angiotensin I, II, III, and noradrenaline. In endothelium-denuded preparations, angiotensin-(1-7) produced a rightward shift of the concentration-effect curves to angiotensin II and noradrenaline. In addition, the inhibition against angiotensin I and II was significantly greater in endothelium-intact preparations [mean median inhibitory concentration (IC50) values for endothelium-intact preparations, 1.25 x 10(-9) M and 1.57 x 10(-9) M for angiotensin I and II, respectively; and for endothelium-denuded preparations, 1.77 x 10(-8) M and 1.17 x 10(-8) M for angiotensin I and II, respectively). Losartan did not affect relaxations in endothelium-intact preparations but caused a significant potentiation of the relaxation by angiotensin-(1-7) in denuded preparations. We conclude that angiotensin-(1-7) is a component of the renin-angiotensin system that acts to modulate the pressor effects of angiotensin II and noradrenaline.

Angiotensin I↗

PubMed1997

Analysis of skin erythema using true-color images.

This article presents a new method for analyzing the spreading of skin erythemas. These occur as a result of the cutaneous vascular axon reflex which can be evoked by a noxious stimulation of the skin. Series of true-color images of the observed skin patch were recorded using a video camera. The images were digitized and stored on computer disk. The delineation of the reddening was segmented for every image of the sequence by a newly developed image processing method. Each image taken after the noxious stimulation was compared with the baseline before the stimulation and each image point was classified as: "unchanged" or "changed skin color." To improve the classification the CIE L*a*b* color space was used. The boundaries of the erythema were extracted from the resulting binary images. Every image of a sequence was analyzed in the same way in order to follow the time course of the flare response. The erythema reaction could be determined in an objective way using this methods. The automatically detected flare sizes were independent of human observers and had a high spatial and temporal resolution. It was used for a crossover study to assess the power of new drugs which modify the blood flow of the skin induced by an intradermal histamine application.

Axons↗

PubMed1997

Experimentally induced pruritus and cutaneous reactions with topical antihistamine and local analgesics in atopic eczema.

We investigated the antipruritic effect of a 15-min application of dimethindene maleate (Fenistil gel) and other local analgesics (Optiderm, EMLA, Xylocain ointment 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis in 12 patients suffering from acute atopic eczema (AE). The results were compared to histamine after pretreatment with the respective placebo and to non-pretreated skin. Wheal and flare areas were planimetrically evaluated. Itch or pain ratings were performed over a 24-min period using a rating scale. The examination also comprised alloknesis, i.e. induction of a perifocal itch sensation by a non-itching mechanical stimulus. None of the antihistaminic and anaesthetic agents reduced the itch intensity significantly. Three of the AE patients had a total lack of alloknesis. We conclude that these substances, when applied for 15 min, are not sufficiently effective in atopic skin suppressing histamine-induced reactions under experimental conditions. The diminished elicitation of alloknesis in these patients may be a result of central nervous system alteration.

Administration, Topical↗

PubMed1997

Role of gender and vascular endothelium in rat aorta response to 17 beta-estradiol.

Estrogen supplementation in postmenopausal women offers significant cardiovascular protection. The mechanism for this benefit is unclear but may be due to an interaction of estrogen with the blood vessel wall (vascular smooth muscle and endothelium). We examined the response of weight-matched female and male endothelium-intact and -denuded aortae to 17 beta-estradiol, its interaction with noradrenaline, and the effect of N-nitro-L-arginine. Estradiol produced relaxation responses that were significantly greater in female endothelium-intact preparations. This response was sensitive to N-nitro-L-arginine, while the response to 17 beta-estradiol in male endothelum-intact and both female and male endothelum-denuded preparations was resistant. Estradiol also inhibited contractions to noradrenaline, which was more pronounced in the female endothelium-intact aortic rings. These data imply that estradiol interacts preferentially with the female vascular endothelium, but there exists an endothelium-independent process that can also be activated in the male aorta. Further studies are warranted to elucidate these differential mechanisms.

Animals↗

PubMed1996

Altered vasodilator response of coronary microvasculature in pacing-induced congestive heart failure.

To characterize vasodilator capacity of small coronary arteries (200-350 microm diameter) in the setting of congestive heart failure, we examined relaxation responses to acetylcholine (10(-9)-10(-4) M) and nitroglycerin (10(-9)-10(-4) M), in the absence and presence of the nitric oxide precursor, L-arginine (10(-4) M). Congestive heart failure was reliably induced in dogs by rapid ventricular pacing (250 beats.min(-1) for 4 weeks). Maximum relaxations (means +/- S.E.) to each vasodilator are expressed as a percentage of the relaxation response to papaverine (10(-4) M). Relaxation responses to the endothelium-dependent relaxing agent, acetylcholine, were not altered at heart failure, or in the presence of L-arginine. Contrary to acetylcholine, relaxations to nitroglycerin were significantly enhanced in heart failure compared to control (83 +/- 25% vs. 25 +/- 6%, respectively, P < 0.05). Although L-arginine, alone, did not cause any vasodilator response in coronary microvessels, it was able to potentiate nitroglycerin relaxations at control (no L-arginine: 25 +/- 6% vs. L-arginine: 135 +/- 66%). In contrast, at heart failure, L-arginine diminished nitroglycerin relaxations (no L-arginine: 83 +/- 25%, vs. L-arginine: 48 +/- 15%). These data indicate a unique vasodilator profile in small coronary arteries at heart failure: endothelium-dependent relaxations are unaltered, whereas responses to nitroglycerin are augmented. Addition of the nitric oxide precursor, L-arginine, did not affect acetylcholine relaxation, yet surprisingly had a differential effect in response to nitroglycerin. Moreover, inhibition of nitric oxide synthase with N(omega)-nitro-L-arginine elicited concentration-dependent constriction in heart failure but not control coronary microvessels. In summary, our study suggests an important role for nitric oxide in vasodilator control of coronary microvessels, which may modify nitrovasodilator therapy in congestive heart failure.

Acetylcholine↗

PubMed1996

Interaction of 5-methyl-urapidil with alpha 1-adrenoceptors in canine blood vessels: impact of pacing-induced heart failure.

This study examines whether the alpha 1-adrenoceptors in canine endothelium-denuded dorsal pedal artery and endothelium-denuded saphenous vein can be differentiated by 5-methyl-urapidil before (non-paced) and at end-stage heart failure induced by rapid ventricular pacing. Noradrenaline and phenylephrine produced concentration-dependent contractions of the dorsal pedal artery and the saphenous vein which were enhanced at end-stage heart failure. In non-paced animals, 5-methyl-urapidil was shown to be insurmountable against noradrenaline with the artery being more sensitive compared to the vein. At end-stage heart failure, 5-methyl-urapidil was a competitive antagonist against noradrenaline in both the artery and the vein with pA2 values of 8.1 (7.9-8.4) and 8.6 (8.2-9.1), respectively. A different antagonist profile was seen against phenylephrine. Similar to noradrenaline, insurmountable antagonism was observed in the artery and the vein before the development of heart failure. In contrast to noradrenaline, at end-stage heart failure, no antagonism was seen with the concentrations of 5-methyl-urapidil tested against phenylephrine. These results suggest that the mechanisms mediating contractions in the dorsal pedal artery and saphenous vein to noradrenaline and phenylephrine are heterogeneous and dependent on the heart failure state.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1996

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Adult↗

PubMed1996

[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation].

No adequate topical therapy is available for pruritus. As little is known about the local influence of antihistamines and topical anaesthetics on the pruritic effect of histamine, we studied these agents in 12 volunteers. The antipruritic effect of 15-min topical application of dimethindene maleate (Fenistil gel) and different agents (Optiderm, EMLA, Xylocaine-Salbe 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis was evaluated. The results were compared with those of pretreatment with the corresponding placebo creams and observations on skin. Wheal and flare areas were evaluated planimetrically. Itch or pain ratings were entered on a scale every minute over a 24-min period. The examination also comprised alloknesis, i.e. elicitation of perifocal itch sensation by usually non-itch-inducing (e.g. mechanical) stimuli. Remarkably, all topically applied substances, regardless of antihistaminic or anaesthetic potential, reduced the area of alloknesis significantly. This is likely to be a result of diminished excitability of the cutaneous mechanoreceptors. Itching was significantly reduced by all active substances, including the placebo cream corresponding to Optiderm, which might be due to the presence of urea.

Adult↗

PubMed1996

Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects.

Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = -0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 +/- 1 vs. +9 +/- 1 mmHg NT vs. BH group), CVP (+0.7 +/- 0.1 vs. +0.5 +/- 0.1 mmHg), HR (+2 +/- 1 vs. +2 +/- 1 beats/min), and MSNA (+5 +/- 1 +4 +/- 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.

Adult↗

PubMed1996

Effect of angiotensin receptor blockade in the rabbit aorta: influence of the endothelium.

Contractile responsiveness of the rabbit aorta (endothelium intact and denuded) to angiotensin I, II, and III was compared. The effects of converting-enzyme inhibition with enalapril, the selective AT1-receptor antagonist (losartan), and the AT2-receptor antagonist (PD 123319) on these contractile profiles were examined. In all preparations, it was found that the angiotensins produced concentration-dependent increases in tension. Differences in sensitivity were encountered; in endothelium-intact preparations, the mean EC50 values (nM with 95% confidence interval in parentheses) for angiotensin I, II, and III were 9 (95% CI 7-11), 40 (20-60), and 30 (10-40), respectively, and for denuded preparations they were 20 (11-29), 0.8 (0.7-0.9), and 30 (20-40), respectively. Enalapril decreased the maximal tension developed to angiotensin I and II, which was greater in endothelium-intact preparations. Losartan was a competitive antagonist against angiotensin I and angiotensin II in both intact and denuded preparations, with pA2 values as follows: against angiotensin I, 9.0 and 9.3 for intact and denuded, respectively; against angiotensin II, 8.3 and 8.9 for intact and denuded, respectively. Losartan antagonized angiotensin III, but the slopes of the Schild analysis were significantly less than unity. In endothelium-intact preparations, PD 123319 failed to significantly antagonize responsiveness to angiotensin I. Against angiotensin II, PD 123319 was a competitive antagonist with a pA2 of 8.3. The antagonism for PD 123319 against angiotensin III was insurmountable. In endothelium-denuded preparations, PD 123319 failed to antagonize angiotensin I and angiotensin III. Although PD 123319 appeared to inhibit the responsivenss of the rabbit aorta by angiotensin II, the slope of the Schild plot was significantly less than unity. These experiments provide evidence that angiotensin I possesses different actions from angiotensin II and III and that a functional endothelium modulates the underlying vascular response to angiotensin. In addition, the endothelium modulates the antagonism by losartan and PD 123319, supporting the notion that the endothelium possesses distinct angiotensin receptors.

Angiotensin I↗

PubMed1995

Inhibition of vascular contractions to alpha-adrenoceptor agonists by polymyxin B: impact of heart failure state.

In this study, the effects of polymyxin B (a protein kinase C inhibitor) on alpha-adrenoceptor stimulation of the canine dorsal pedal artery and saphenous vein were examined. In addition, the question was asked, whether these effects could be altered by the impact of a heart failure state? Blood vessels were obtained at three time points during the development of pacing-induced heart failure in the dog; control (non-paced), 1 week paced and end-stage heart failure. Concentration-effect curves were constructed to the alpha-adrenoceptor agonists, namely, noradrenaline and phenylephrine in the absence and presence of polymyxin B (2 x 10(-5) and 10(-4) M). Responses to noradrenaline and phenylephrine were enhanced in the saphenous vein, but not in the dorsal pedal artery, following the onset of heart failure. In the dorsal pedal artery, polymyxin B was found to inhibit the contractions developed to noradrenaline and phenylephrine to a significant degree (P < 0.05) at control and end-stage heart failure. In contrast, in the saphenous vein, polymyxin B inhibited responses developed to noradrenaline and phenylephrine at all time points studied. This inhibition was always more marked against noradrenaline compared to phenylephrine and, similar to the dorsal pedal artery, became more pronounced at end-stage heart failure. Furthermore, the vein was always more sensitive compared to the artery. Interestingly, as heart failure developed, a non-classical broad concentration-effect curve was evident. The high affinity component was more sensitive to inhibition by polymyxin B. This component was absent at end-stage heart failure in response to phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Neurogenic flare responses are heterogeneous in superficial and deep layers of human skin.

Infrared thermography and video image analysis were used to compare the development of the neurogenic flare response in deep and superficial skin layers. Neurogenic vasodilatation was induced by injection or iontophoretic application of histamine. Thermograms were recorded every 10 s to evaluate the local warming reaction. Color-video image analysis was used for computerized delineation of the visible flare. Images derived from video analysis were superimposed to the thermograms after linear transformation. The thermal reaction started within 10 s simultaneously at 2-5 distinct spots after histamine application at distances of 4-25 mm from the application site while the flare reaction seemed to spread from the application site when it became visible after a delay often exceeding 20 s. The visible flare but not the warming reaction was suppressed by topically applied local anesthetic (EMLA). Warming at focal spots was also observed during post-occlusive hyperemia. About 70% of these spots were identical to those activated by histamine. The results indicate that the vascular axon reflex is differently organized in different layers of the skin.

Adult↗

PubMed1995

Delayed responses to electrical stimuli reflect C-fiber responsiveness in human microneurography.

The slowing of impulse conduction during the relative refractory period has often been used to assess activation of C-fibers, in particular, in human microneurography. This study aimed to evaluate the sensitivity of this method and the factors affecting it. Thirty cutaneous C-fibers were recorded from the peroneal nerves of healthy human subjects. Intracutaneous electrical stimulation in the receptive field at 4 s intervals, after some minutes of adaptation, induced spike discharges at constant latency. One or more conditioning stimulus pulses were interpolated at different intervals and the increase in latency after the subsequent regular pulse was assessed. The latency shift was found to depend on the number of interposed pulses, on the time interval between conditioning and conditioned stimulus, and on the conduction velocity of the C-unit. The increase in latency was larger with greater distance between stimulating and recording electrodes, indicating a contribution of the conductile membrane over its whole length. On the other hand, slowing was more pronounced, on average, in slower conducting C-units and conduction velocities were slower when recordings were performed more distally. These findings indicate that the slower terminal nerve branches contribute most to the latency increases. Even a single additional spike in between two regular pulses caused a reliable latency shift of 1.2 +/- 0.2 ms (mean +/- SEM) and additional pulses lead to an approximately linear latency increase (2 pulses: 2.3 +/- 0.3 ms; 4 pulses: 5.9 +/- 0.7 ms). In contrast to the number of interposed stimuli, different intervals between interposed and regular stimuli had only a minor impact on the latency shifts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Differential effects of spinalization on discharge patterns and discharge rates of simultaneously recorded nociceptive and non-nociceptive spinal dorsal horn neurons.

Recordings were made simultaneously from 2-5 neurons at the same site in the lumbar spinal dorsal horn of pentobarbital-anesthetized rats. Neurons were classified as low-threshold (LT) or multireceptive (MR) according to their responses to non-noxious mechanical or noxious radiant heat stimuli of the skin. At the same recording sites neurons could be encountered which belong to different classes and/or which had mechanoreceptive fields which did not overlap. Cold blocks of the upper or lower thoracic cord or transsections of the upper cervical cord were made to evaluate the effects of spinalization on both the rate and pattern of background activity and/or noxious heat-evoked responses of different dorsal horn neurons under identical experimental conditions. At 24 of 27 recording sites, spinalization had qualitatively or quantitatively different effects on the rate of background activity of simultaneously recorded neurons. Interspike interval (ISI) means of background activity were significantly reduced in 29 of 65 (44.6%) neurons, prolonged in 23 of 65 (35.4%) neurons, or unchanged in 13 of 65 (20%) neurons. MR neurons displayed a significantly higher incidence of decreased background activity 17 of 45 (37.8%) and a lower incidence of increased background activity (18 of 45, 40%) during spinalization than the LT neurons from which 1 of 12 (8.3%) decreased and 8 of 12 (66.6%) increased background activity. Almost all (95.4%) neurons changed their discharge patterns after spinalization. At 9 of 27 recording sites, the discharge patterns of simultaneously recorded neurons were affected differently by spinalization as revealed by the coefficient of dispersion of the interspike intervals (ISI), indicating changes in the tendency to discharge action potential in clusters (bursts). At the same recording sites the level of noxious heat-evoked responses of simultaneously recorded MR neurons was also differentially affected by spinalization. Nociceptive responses were significantly enhanced in 19 of 37 (51.4%) neurons (137.8 +/- 142.6% of control, mean +/- SD), reduced in 13 of 37 neurons (35.1%) (by 58.9 +/- 20.9%) and/or unchanged in 5 of 37 (13.5%) neurons. It is concluded that no general 'tone' of descending antinociception exists and that tonic descending excitatory and inhibitory systems may be active simultaneously modulating both the level and pattern of neuronal discharges.

Animals↗

PubMed1995

Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man.

A new experimental procedure was developed to quantify the analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs) in healthy human subjects. In order to mimic the clinical situation, the drug was 'therapeutically' administered 1 day after induction of inflammation by freezing a small skin area. The procedure was easily tolerated and led to a marked hyperalgesia without ongoing pain which was tested using mechanical impact stimulation and magnitude estimation. For comparison, we used a previously established model of repeated noxious pinching of an interdigital skin web which induces a hyperalgesia to pressure (rated via visual analogue scale), and topical application of capsaicin which leads to quantifiable flare and allodynia responses. The effects of a cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800 mg at 2-h intervals) were tested versus placebo using a double-blind cross-over design with 24 volunteers of either gender. Ibuprofen caused a significant suppression of the hyperalgesia to repeated pinching and of the hyperalgesia to impact stimulation following freeze trauma. In contrast, there was no effect on the areas of flare and allodynia induced by capsaicin application and on the impact evoked sensations from untreated skin. The two dosages of ibuprofen, however, appeared to be equally effective in a way that suggests a plateauing of the antihyperalgesic effect. The two models in which hyperalgesia is affected by ibuprofen, i.e., repeated pinching and impact stimulation after freeze trauma, seem to provide comparable sensitivity. The freeze model may in the future have the advantage to allow for a better temporal resolution of the drug's action profile.

Adult↗