Biomedical subjects

J C Willer

Publications and source records attributed to J C Willer.

At least 37 records · Page 2Linked to original sources

PubMed1998

Electrophysiological determination of the site involved in generating abnormal muscle responses in hemifacial spasm.

In patients with hemifacial spasm (HFS), abnormal muscle responses due to abnormal cross-transmission are observed in facial muscles. However, the site in the facial nerve responsible for the cross-transmission remains a matter of controversy. We have developed a model in which by considering the electrophysiological parameters involved in producing the abnormal muscle response, we can determine the site of the abnormal cross-transmission within the facial nerve. This model was applied to HFS patients with three different etiologies: idiopathic, post-Bell's palsy, and post-XII-VII anastomosis. Our data show that: in idiopathic HFS, the cross-transmission may occur in the facial nerve at the level of the pontocerebellar angle; in post-Bell's palsy, it is inside the petrous bone; and in XII-VII anastomosis, it must be in the extracranial part of the facial nerve. The possible mechanisms for this cross talk are discussed in terms of ephaptic transmission or of a central hyperexcitability in the facial motor nucleus.

Adult↗

PubMed1998

Transcutaneous electrical nerve stimulation: effect on peripheral nerve conduction, mechanical pain threshold, and tactile threshold in humans.

OBJECTIVES: To investigate the effect of different transcutaneous electrical nerve stimulation (TENS) parameters on nerve conduction in the human superficial radial nerve and on peripheral mechanical pain threshold (MPT) and tactile threshold (TT), and to further the current knowledge of the neurophysiologic effects of TENS. STUDY DESIGN: Fifty healthy human subjects were randomly allocated in equal numbers to a control group or one of four TENS groups to receive electrical stimulation consisting of four combinations of TENS pulse durations (50microsec and 200microsec) and frequencies (4Hz and 110Hz). In the TENS groups, TENS was applied under double-blind conditions for 15 minutes over the superficial radial nerve in the dominant forearm. Over a 1-hour period, compound action potentials, MPT readings, and TT readings were recorded bilaterally. RESULTS: Only one combination of TENS parameters (110Hz, 200microsec) effected consistent changes in all of the variables assessed, ie, TENS produced a significant increase in negative peak latency while simultaneously increasing both MPT and TT. CONCLUSION: The findings from this study suggest that at least part of TENS-mediated hypoalgesia is a consequence of a direct peripheral effect of TENS, although a "central" effect may not be excluded.

Adult↗

PubMed1998

Depressive effects of segmental and heterotopic application of transcutaneous electrical nerve stimulation and piezo-electric current on lower limb nociceptive flexion reflex in human subjects.

OBJECTIVES: To evaluate quantitatively the effectiveness and clinical relevance of various parameters of electrical stimulation used to relieve acute and chronic pain and to further knowledge of the mechanisms that may underlie the physiologic response produced by the transcutaneous application of each type of current. DESIGN: A nociceptive flexion reflex (RIII reflex) elicited in the lower limb by electrical stimulation of the sural nerve at the ankle was studied before, during, and after application of the following conditioning stimuli: (1) non-noxious transcutaneous electrical nerve stimulation (TENS)--low-intensity (2mA), short-duration (0.1 msec), and high-frequency (100Hz) rectangular pulses (TENS1); (2) noxious TENS--high-intensity (20mA), long-duration (2 msec), and low-frequency (3Hz) rectangular pulses (TENS2); (3) noxious piezo-electric current (PEC)--high-voltage, low-charge, low-intensity, and low-frequency rectangular pulses delivered by a piezo-electric ceramic device (PECs1); (4) a sham PEC situation in which the piezo-electric device did not produce any electric current (Sham PEC). Each conditioning stimulus (TENS1, TENS2, PECs1, Sham PEC) was applied for a 2-minute period either segmentally on the sural nerve itself or heterotopically on the skin overlying the first interosseous space of the contralateral hand. PARTICIPANTS: Twenty-four healthy volunteers (14 women, 10 men, 19 to 52 years of age), who were briefed and familiarized with the experimental procedure. During the experimental sessions, subjects were prone in bed to ensure muscular relaxation. MEASURES: Value of the nociceptive RIII reflex before, during, and after application of conditioning stimuli in the four procedures described above. This reflex was selected because it has been shown to be an objective and physiologic correlate of pain. RESULTS: Non-noxious TENS1 stimulation applied segmentally produced inhibitions of the RIII reflex only during the 2-minute conditioning period. When given segmentally, the noxious TENS2 stimulation produced a facilitatory effect during the 2 minutes of application, followed by significant inhibitory after-effects. The administration of TENS2 heterotopically resulted in inhibitions of the RIII reflex both during and after the 2-minute conditioning period. Application of PECs1, whether segmentally or heterotopically, produced powerful and long-lasting inhibitory after-effects, especially with the heterotopic paradigm. These effects were associated with long-lasting local changes to the skin of the neurogenic inflammation type, which were well tolerated by all subjects. Application of Sham PEC did not result in significant modification of either the RIII reflex or the skin. CONCLUSIONS: These data are discussed in terms of possible spinal and supraspinal mechanisms involving inhibitory descending controls and underline the potential clinical use of PECs1 in the treatment of pain.

Adult↗

PubMed1998

Effects of rectal distensions on nociceptive flexion reflexes in humans.

We previously showed that gastric distension inhibits the somatic nociceptive flexion RIII reflex. To explore further the viscerosomatic interactions, we tested in the present study the effects of rectal distensions on RIII reflexes. Rapid and slow-ramp rectal distensions were performed in 10 healthy volunteers with an electronic barostat. The RIII reflex was continuously recorded from the lower limb during both types of distension and from the upper limb during rapid distensions. The visceral sensations were scored on a graded questionnaire. Rapid distensions facilitated the RIII reflex recorded from the lower limb, but at the highest distension level, facilitation was followed by inhibition. Slow-ramp distension induced gradual inhibition of the RIII reflex, which correlated with both distension volume and visceral sensation. RIII reflex recorded from the upper limb was also inhibited by rapid rectal distensions. Reflex inhibitions were probably related to the activation of pain modulation systems. One plausible explanation for the facilitatory effects, observed only at the lower limb, is the convergence of rectal and reflex afferents at the same levels of the spinal cord. The differential effects of rapid and slow-ramp distensions suggest the activation of two distinct populations of mechanoreceptors by these two modes of distension.

Adult↗

PubMed1998

Facilitation of a nociceptive flexion reflex in man by nonnoxious radiant heat produced by a laser.

Electromyographic recordings were made in healthy volunteers from the knee-flexor biceps femoris muscle of the nociceptive RIII reflex elicited by electrical stimulation of the cutaneous sural nerve. The stimulus intensity was adjusted to produce a moderate pricking-pain sensation. The test responses were conditioned by a nonnoxious thermal (</=40 degrees C) stimulus applied to the receptive field of the sural nerve. This stimulus was delivered by a CO2 laser stimulator and consisted of a 100-ms pulse of heat with a beam diameter of 20 mm. Its power was 22.7 +/- 4.2 W (7.2 mJ/mm2), and it produced a sensation of warmth. The maximum surface temperature reached at the end of the period of stimulation was calculated to be 7 degrees C above the actual reference temperature of the skin (32 degrees C). The interval between the laser (conditioning) and electrical (test) stimuli was varied from 50 to 3, 000 ms in steps of 50 ms. It was found that the nociceptive flexion reflex was facilitated by the thermal stimulus; this modulation occurred with particular conditioning-test intervals, which peaked at 500 and 1,100 ms with an additional late, long-lasting phase between 1,600 and 2,300 ms. It was calculated that the conduction velocities of the cutaneous afferent fibers responsible for facilitating the RIII reflex, fell into three ranges: one corresponding to A delta fibers (3.2 m/s) and two in the C fiber range (1.3 and 0.7 m/s). It is concluded that information emanating from warm receptors and nociceptors converges. In this respect, the present data show, for the first time, that in man, conditioning nonnociceptive warm thermoreceptive A delta and C fibers results in an interaction at the spinal level with a nociceptive reflex. This interaction may constitute a useful means whereby signals add together to trigger flexion reflexes in defensive reactions and other basic motor behaviors. It also may contribute to hyperalgesia in inflammatory processes. The methodology used in this study appears to be a useful noninvasive tool for exploring the thermoalgesic mechanisms in both experimental and clinical situations.

Adult↗

PubMed1998

Quantitative study of Stewart-Holmes test.

Stewart-Homes test (SHT) is an ordinary neurological test performed for the diagnosis for cerebellar disease. We developed a quantitative method based on SHT carried out on the upper limb. Nineteen cerebellar patients and fifteen volunteer healthy subjects were tested. During the test, acceleration of forearm and two associated surface EMGs over biceps and triceps brachialis were recorded and analyzed. (1) Acceleration curve showed an oscillating pattern with flexion and extension over the elbow in both groups, but in cerebellar patient group, the acceleration oscillation wave was more pronounced and latencies of peak acceleration were significantly longer. (2) Correspondingly, the EMGs timing parameters were also different between the two groups: in patient group, ceasing isometric biceps contraction was delayed; rebound EMGs bursts over both biceps and triceps were prolonged. (3) Modelization of the oscillation of acceleration curve with dampened oscillation model showed that in patient group the oscillating amplitude attenuated much more slowly than in control group. A standard curve was established for detecting the acceleration profile abnormalities of SHT in cerebellar patients.

Adult↗

PubMed1997

Putative projection of phrenic afferents to the limbic cortex in humans studied with cerebral-evoked potentials.

Respiratory sensations may rely in part on cortical integration of respiratory afferent information. In an attempt to study such projections, we recorded evoked potentials at scalp and cervical sites in 10 normal volunteers undergoing transcutaneous phrenic stimulation (0.1-ms square pulses, intensity liminal for diaphragmatic activation, series of 600 shocks at 2 Hz). A negative cerebral component of peak latency (12.79 +/- 0.54 ms; N13) was constant, and a negative spinal component (7.09 +/- 1.04 ms; N7) could also be recorded, all results being reproducible over time. Monitoring of cardiac frequency, skin anesthesia, and stimulation adjacent to the phrenic nerve made the phrenic origin of N7 and N13 the foremost hypothesis. Increasing stimulation frequency and comparison with median nerve stimulation provided arguments for the neural nature of the signals and their cerebral origin. Recordings from intracerebral electrodes in a patient showed a polarity reversal of the evoked potentials at the level of the cingulate gyrus. In conclusion, phrenic stimulation could allow one to study projections of phrenic afferents to the central nervous system in humans. Their exact site and physiological meaning remain to be clarified.

Adult↗

PubMed1997

Temporal summation of C-fiber afferent inputs: competition between facilitatory and inhibitory effects on C-fiber reflex in the rat.

Long-lasting facilitations of spinal nociceptive reflexes resulting from temporal summation of nociceptive inputs have been described on many occasions in spinal, nonanesthetized rats. Because noxious inputs also trigger powerful descending inhibitory controls, we investigated this phenomenon in intact, halothane-anesthetized rats and compared our results with those obtained in other preparations. The effects of temporal summation of nociceptive inputs were found to be very much dependent on the type of preparation. Electromyographic responses elicited by single square-wave electrical shocks (2 ms, 0.16 Hz) applied within the territory of the sural nerve were recorded in the rat from the ipsilateral biceps femoris. The excitability of the C-fiber reflex recorded at 1.5 times the threshold (T) was tested after 20 s of electrical conditioning stimuli (2 ms, 1 Hz) within the sural nerve territory. During the conditioning procedure, the C-fiber reflex was facilitated (wind-up) in a stimulus-dependent fashion in intact, anesthetized animals during the application of the first seven conditioning stimuli; thereafter, the magnitude of the responses reached a plateau and then decreased. Such a wind-up phenomenon was seen only when the frequency of stimulation was 0.5 Hz or higher. In spinal, unanesthetized rats, the wind-up phenomenon occurred as a monotonic accelerating function that was obvious during the whole conditioning period. An intermediate picture was observed in the nonanesthetized rat whose brain was transected at the level of the obex, but the effects of conditioning were profoundly attenuated when such a preparation was anesthetized. In intact, anesthetized animals the reflex was inhibited in a stimulus-dependent manner during the postconditioning period. These effects were not dependent on the frequency of the conditioning stimulus. Such inhibitions were blocked completely by transection at the level of the obex, and in nonanesthetized rats were then replaced by a facilitation. A similar long-lasting facilitation was seen in nonanesthetized, spinal rats. It is concluded that, in intact rats, an inhibitory mechanism counteracts the long-lasting increase of excitability of the flexor reflex seen in spinal animals after high-intensity, repetitive stimulation of C-fibers. It is suggested that supraspinally mediated inhibitions also participate in long term changes in spinal cord excitability after noxious stimulation.

Animals↗

PubMed1997

Effects of intrathecal or intracerebroventricular administration of nonsteroidal anti-inflammatory drugs on a C-fiber reflex in rats.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.

Animals↗

PubMed1996

Effects of clonidine on a C-fibre reflex in the rat.

A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anaesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The intravenous administration of 0.02-0.2 mg/kg clonidine resulted in a dose-dependent depression of the C-fibre reflex. The alpha 2-adrenoceptor antagonist idazoxan completely prevented this depressive effect of clonidine. The effects of clonidine on the C-fibre reflex elicited by a wide range of stimulus intensities were investigated using recruitment curves: following 0.16 mg/kg clonidine, a dramatic shift of the recruitment curve to the right was seen with both an increase in the threshold and a decrease in the slope. Clonidine also produced a dose-dependent increase in blood pressure, but this was not correlated with the depression of the nociceptive reflex.

Adrenergic alpha-Agonists↗

PubMed1996

Effect of the kappa agonist fedotozine on perception of gastric distension in healthy humans.

BACKGROUND AND AIM: Gastric hypersensitivity to mechanical distension has been observed in functional dyspepsia, but no drug is available that specifically acts on gastric afferent pathways to decrease gastric nociception. The aim of this study was to assess the effect of fedotozine, a synthetic ligand for peripheral kappa receptors, on human gastric sensitivity. METHODS: Twenty-seven healthy volunteers were randomized to receive either fedotozine (30 mg t.d.s.) or a placebo, for 7 days. On day 7, the effects of fedotozine were tested on discomfort threshold and gastric compliance during graded isobaric and isovolumic distensions. In 16 of these subjects, the effect of this drug was tested on somatic sensitivity. In 10 other healthy volunteers the effect of fedotozine on gastric distension-induced inhibition of the RIII reflex, a process closely related to visceral sensitivity, was also studied. RESULTS: During isobaric distensions, the discomfort threshold was significantly higher in subjects on fedotozine than in those on placebo (14.4 +/- 0.92 vs. 12.0 +/- 1.13 mmHg; P = 0.04). Compared to placebo, fedotozine did not modify gastric compliance and somatic sensitivity. Fedotozine also reduced the inhibition of the RIII reflex induced by gastric distension. CONCLUSION: Fedotozine decreases gastric sensitivity to distension by exerting specific action on gastric afferent pathways.

Adult↗

PubMed1996

A clinical and neurophysiological study of a patient with an extensive transection of the spinal cord sparing only a part of one anterolateral quadrant.

In 1976, Noordenbos and Wall studied sensory functions in a woman with a surgically verified T3 spinal cord transection which spared only a part of the left anterolateral quadrant, We re-investigated this unique case 18 years after the lesion and included a comparable sensory examination, MRI of the spinal cord, somatosensory evoked potentials, PET-activation study during hand and foot vibration and analysis of flexion reflex modulation during the Jendrassik manoeuvre. Our results show that the residual anterolateral quadrant contains ascending pathways carrying a wide range of sensory information as well as descending pathways modulating flexion reflex activity at the spinal level. Moreover, the changes in sensory functions and the unique pattern of cortical activation suggest a functional reorganization of the connectivity between the periphery and the cerebral cortex. Changes of facilitation and/or of inhibition at different levels of the somatosensory system may account for these longterm plastic changes.

Evoked Potentials, Somatosensory↗

PubMed1996

Effects of intravenous nonsteroidal antiinflammatory drugs on a C-fiber reflex elicited by a wide range of stimulus intensities in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.v. administration of aspirin, indomethacin, ketoprofen, paracetamol (= acetaminophen) and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex by up to 30 to 40%. By contrast, saline was ineffective. High doses of the effective drugs that produced large disturbances in heart rate and/or acid-base equilibrium were not considered in the pharmacological analysis. When a constant level of stimulation was used, different dose-dependent profiles of drug action were observed. Aspirin induced a slow and gradual depression, although indomethacin, ketoprofen and paracetamol produced a peak effect within the first 10-min period and then reached a steady state phase for up to 30 min. The depressive effects of lysine clonixinate appeared more stable. When recruitment curves were built with a range of nociceptive stimulus intensities, all the drugs produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without any major modification in the thresholds. The order of potency was the same for both stimulation paradigms, e.g., aspirin < paracetamol < lysine clonixinate = ketoprofen < indomethacin. It is concluded that NSAID elicit significant antinociceptive effects at a central level, which do not depend on the existence of a hyperalgesic or inflammatory state.

Animals↗

PubMed1996

[Sympathetic skin responses and variability of the R-R interval: correlation with the severity stages of diabetic polyneuropathy].

The sympathetic skin responses (SSR) and the variations of the R-R interval of the electrocardiogram (the difference between the maximum and minimum heart rates at rest, the ratio between the maximum and minimum heart rates during the Valsalva manoeuvre or Valsalva ratio, and during an active orthostatic test or orthostatic ratio) have been measured in 32 control subjects and 53 diabetic patients. These latter ones were classified according to the existence and the increasing severity of a polyneuropathy (PNP) into 4 grades (0 to III) based on Dyck's classification modified depending on the presence or the absence of cutaneous impairments in grade II. There was an important inter-individual variability for SSR as well as R-R interval results, in the control group. In the absence of PNP, the vegetative tests showed normal values. These tests were severely degraded in the diabetic patients with a PNP grade III, ov even could not be performed. The SSR amplitude was decreased in all diabetic patients. In the presence of clinical signs of dysautonomia, the SSR amplitude, the heart rate variability at rest and the orthostatic ratio were significantly different from those of the control subjects. The presence of trophic disorders appearing at PNP grade II did not significantly modify the results of the tests. Although they did not allow any differentiation of the PNP intermediary grades. SSR and R-R intervals are of interest in appreciating the infra-clinical existence and the importance of the neurovegetative disorders occurring during diabetic polyneuropathies.

Adrenergic Fibers↗

PubMed1995

Buprenorphine blocks diffuse noxious inhibitory controls in the rat.

A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anaesthetised rats. Such reflex responses can be inhibited by applying noxious conditioning stimuli to heterotopic areas of the body. These inhibitory processes have been termed diffuse noxious inhibitory controls. The responses were recorded before, during and after the immersion of the tail in a thermoregulated waterbath (at 50 degrees C) for 1 min. The C-fibre reflex responses were depressed by a maximum of 71 +/- 3% at 45 s after the start of such conditioning stimuli. A dose of 3 mu g/kg buprenorphine completely blocked the inhibition and post-stimulus effects triggered by the heterotopic noxious stimuli. In the 0.3-3 mu g/kg range, buprenorphine increased, in a dose-dependent manner, the magnitude of the inhibition. These doses did not produce any changes in the C-fibre reflex itself. The results are discussed in terms of the mechanisms underlying the analgesic properties of buprenorphine.

Analgesics, Opioid↗

PubMed1995

Partial restoration of blink reflex function after spinal accessory-facial nerve anastomosis.

Functional motor control requires perfect matching of the central connections of motoneurons with their peripheral inputs. It is not known, however, to what extent these central circuits are influenced by target muscles, either during development or after a lesion. Surgical interventions aimed at restoring function after peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. A patient was studied in whom the spinal accessory nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralysed muscles. This procedure, in addition to replacing the facial neurons at peripheral synapses, allowed a new short latency trigeminospinal accessory reflex of the R1 blink reflex type to be demonstrated, implying that trigeminal neurons had sprouted towards spinal accessory motoneurons over a distance of at least 1 cm. These results show an unexpected influence of the periphery in remodelling central connectivity in humans. The motoneuronal excitability for this R1 reflex response was therefore studied to compare the convergent properties of facial motoneurons (normal side) with those of the spinal accessory motoneurons (operated side) using a classic double shock technique with variable interstimulus intervals (conditioning test stimulus). On the normal side, conditioning stimuli (to the ipsilateral or contralateral infraliminar supraorbital nerve) produced a clearcut facilitation of the R1 blink reflex when the interstimulus interval was 30-80 ms. By contrast, a similar procedure had no effect on the R1 blink reflex mediated via the trigeminal-spinal accessory reflex arc. These data indicate that despite the heterotopic sprouting of some axons from neurons in the XIth nucleus, motoneurons involved in the newly formed reflex arc remain totally inexcitable by other trigeminal afferents and seem unable to ensure a physiological functioning of the normal blink reflex. Thus the functional relevance of the recovered R1 blink response remains unclear.

Accessory Nerve↗

PubMed1995

Effects of intrathecal and intracerebroventricular buprenorphine on a C-fiber reflex in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the ipsilateral sural nerve, was recorded from the biceps femoris muscle in anesthetized rats. The temporal evolution of the reflex was studied using a constant level of stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. Intrathecal doses of buprenorphine in the 0.2 to 10 micrograms range, elicited a facilitation of the C-fiber reflex in a dose-dependent manner. A large dose (100 micrograms) depressed but did not block the reflex. Intracerebroventricular doses of buprenorphine in the 0.1 to 10 micrograms range, facilitated the C-fiber reflex. A higher dose (100 micrograms) elicited a biphasic effect: depressive when the stimulus intensity was weak and facilitatory when the stimulus intensity was strong. It is concluded that the antinociceptive properties of buprenorphine cannot be related to a direct or indirect depressive spinal effect. In terms of spinal and supraspinal effects of buprenorphine, it is likely that buprenorphine facilitates the C-fiber reflex via a supraspinal mechanism that acts on sensory and/or motor components of the reflex arc although the depression of the reflex involves a spinal mechanism. The lipophilic properties of buprenorphine could explain a substantial diffusion from its spinal injection site to the brain. From a clinical standpoint, this study confirms that intrathecal administration of buprenorphine is an inadequate way of accessing spinal opioid receptors.

Analgesics, Opioid↗

PubMed1995

Effects of intravenous morphine and buprenorphine on a C-fiber reflex in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied by using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying the stimulus intensity from 0 to 7 x threshold. Low (0.5-1 mg/kg) and high doses (4-10 mg/kg) of i.v. morphine induced a facilitation and a depression of the C-fiber reflex, respectively, in a dose-dependent manner. The ED50 (95% confidence limit) for the depressive effect with a stimulus intensity of 3 x control threshold was 3.8 (3.1-4.8) mg/kg. Increasing the stimulus intensity was associated with a shift of the dose-response curve to the right, without a change of slope. In the 1.5 to 7 x threshold range, ED50 were linearly related to the stimulus intensity. Intravenous naloxone (0.4 mg/kg) completely antagonized the facilitation or depression induced by morphine. Low doses (1-10 micrograms/kg; i.v.) of buprenorphine facilitated the reflex in a fashion similar to morphine. Higher doses (30-1000 micrograms/kg; i.v.) elicited a biphasic effect on the C-fiber reflex: depressive and facilitatory with weak and strong stimulus intensities, respectively. These results are discussed in terms of there being an intrinsic efficacy for the depressive effects of morphine and buprenorphine and of their clinical potencies. Various hypotheses are suggested regarding the facilitations of the C-fiber reflex.

Animals↗