Ascending afferent regulation of rat midbrain dopamine neurons

Standard, extracellular single-unit recording techniques were used to examine the electrophysiological and pharmacological responsiveness of midbrain dopamine (DA) neurons to selected, ascending afferent inputs. Sciatic nerve stimulation-induced inhibition of nigrostriatal DA (NSDA) neurons was blocked by both PCPA (5-HT synthesis inhibitor) and 5,7-DHT (5-HT neurotoxin), suggesting mediation by a serotonergic (5-HT) system. Direct stimulation of the dorsal raphe (which utilizes 5-HT as a neurotransmitter and inhibits slowly firing NSDA neurons) inhibited all mesoaccumbens DA (MADA) neurons tested. Paradoxically, DPAT, a 5-HT1A agonist which inhibits 5-HT cell firing, enhanced sciatic nerve stimulation-induced inhibition of NSDA neurons. MADA neurons were not inhibited by sciatic nerve stimulation and, therefore, could not be tested in this paradigm. In contrast to the dorsal raphe, electrical stimulation of the pedunculopontine tegmental nucleus preferentially excited slowly firing NSDA and MADA neurons. Thus, both excitatory and inhibitory ascending afferents influence the activity of midbrain DA neurons, and intact 5-HT systems are necessary for sciatic nerve stimulation to alter DA cell activity. However, the role that 5-HT plays in mediating peripheral sensory input remains unclear.     

Functional properties of spinal interneurons activated by muscular free nerve endings and their potential contributions to the clasp-knife reflex

1. The goal of this study was to characterize the functional properties of spinal interneurons that are excited by muscular free nerve endings and to assess their contributions to the clasp-knife reflex. 2. The patterns of activity of 82 spinal interneurons that were excited by squeezing the Achilles tendon or manipulation of the muscle surfaces, preferential stimuli for muscular free nerve endings, were extracellularly recorded in lamina V-VII of the L5-S1 spinal cord in decerebrated and spinalized cats. 3. Interneurons were uniformly excited by increases in muscular length and force. Responses to muscle stretch exhibited gradual decay during maintained stretch, afterdischarge after stretch release, and adaptation to repeated stretch. Responses to isometric contraction induced by electrical stimulation of motor axons was also prolonged after contraction, but did not decay during maintained contraction. For similar increases in force, stretch evoked greater excitation than contraction, indicating that both stretch and contraction contributed to interneuronal activity. Overall, the time course and magnitude of the interneuronal responses to stretch and contraction paralleled the time course and magnitude of the clasp-knife reflex. 4. Interneurons were powerfully excited by muscular free nerve endings, which mediate the clasp-knife reflex, and by cutaneous receptors. Only occasionally were they excited by primary spindle or Golgi tendon organ afferents, which suggests that activation of muscular free nerve endings mediated the interneuronal responses to stretch and contraction. 5. Simultaneous recordings of interneuronal activity and the clasp-knife reflex revealed a broad correlation between interneuronal activity and clasp-knife inhibition. 6. Because the patterns of activity of free nerve ending-responsive interneurons during stretch and contraction were similar to the clasp-knife reflex, were closely correlated with clasp-knife inhibition during simultaneous interneuronal and reflex recordings, and were powerfully excited by muscular free nerve endings, it is likely that the interneurons described above contributed to the clasp-knife reflex. 7. In contrast, a small number (n = 16) of interneurons were recorded that were only weakly excited by muscular free nerve endings but strongly excited by group I afferents, exhibited less spontaneous and evoked activity, and had significantly different responses to stretch and contraction. These interneurons are less likely to have contributed to the clasp-knife reflex.     

The role of pubococcygeus muscle in urinary continence in the male rat

The role of the male rat pubococcygeus muscle (Pcm) in the micturition reflex was analyzed. Anatomical features of Pcm, electrical stimulation of its nerve, electrical recording and stimulation of the muscle and cystometrograms were carried out. Results showed that Pcm has fibers attached to the ventrolateral part of the external urethral sphincter, and that its activity contributes to hold the tail in the midline. Pcm shows activity during fluid expulsion in cystometrograms and spontaneous micturitions. This activity produced reflex inhibition of detrusor contraction and was not the cause of intravesical high frequency oscillations. Thus, it is proposed that Pcm activity produces the discharge of its afferents which in turn activates a spinal reflex to promote continence.     

Somatotopic redistribution of c-fos expressing neurons in the superficial dorsal horn after peripheral nerve injury

The functional somatotopic reorganization of the lumbar spinal cord dorsal horn after nerve injury was studied in the rat by mapping the stimulus-evoked distribution of neurons expressing proto-oncogene c-fos. In three different nerve injury paradigms, the saphenous nerve was electrically stimulated at C-fibre strength at survival times ranging from 40 h to more than six months: 1) Saphenous nerve stimulation from three weeks onwards after ipsilateral sciatic nerve transection resulted in an increase in the number of Fos-immunoreactive neurons within the dorsal horn saphenous territory in laminae I-II, and an expansion of the saphenous territory into the denervated sciatic territory until 14 weeks postinjury. 2) Saphenous nerve stimulation from five days onwards after ipsilateral sciatic nerve section combined with saphenous nerve crush resulted in an increase in the number of Fos-immunoreactive neurons within the dorsal horn saphenous nerve territory, and an expansion of the saphenous nerve territory into the denervated sciatic nerve territory. 3) Stimulation of the crushed nerve (without previous adjacent nerve section) at five days, but not at eight months resulted in a temporary increase in the number of Fos-immunoreactive neurons within the territory of the injured nerve, and no change in area at either survival time. The results indicate that nerve injury results in an increased capacity of afferents in an adjacent uninjured, or regenerating nerve, to excite neurons both in its own and in the territory of the permanently injured nerve in the dorsal horn. The onset and duration of the increased postsynaptic excitability and expansion depends on the types of nerve injuries involved. These findings indicate the complexity of the central changes that follows in nerve injuries that contain a mixture of uninjured, regenerating and permanently destroyed afferents.     

Kinetic characterisation and solubilisation of gamma-hydroxybutyrate receptors from rat brain

The effects of single electrical shocks to myelinated A and unmyelinated C afferent fibers of perineal and limb somatic nerves on the reflex discharges in pelvic parasympathetic (L6/S1) efferent nerves to the bladder were examined in anesthetized central nervous system (CNS)-intact and acute spinal rats. When the bladder was empty, stimulation of perineal somatic inputs to the L6 and S1 segments from the perineo-femoral branch of a pudendal nerve produced excitatory A- and C-reflex discharge components in postganglionic parasympathetic efferent nerve branches on the bladder surface. When the bladder was expanded and pelvic efferent neurons were rhythmically active, additional inhibitory A- and C-reflex components could be seen. After acute spinal transection, the same stimuli elicited excitatory A- and C-reflex discharges of similar latency as those observed before the spinal transection, but were of larger amplitude and longer duration; resting activity in the pelvic nerve was low, and no evoked inhibitory reflex components could be observed. Electrical stimulation of afferents in the tibial nerve had no effect when the bladder pressure was low, but when the bladder was distended, early and late components of reflex inhibition and excitation of parasympathetic activity were visible in CNS-intact rats; these reflex responses were abolished following spinalization.     

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.     

A phylogenetic assessment of the eukaryotic light-harvesting antenna proteins, with implications for plastid evolution

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70-95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0-2.5x perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be -- at least partly -- mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2x motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50-80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking.     

Effects of excitation of sensory pathways on the membrane potential of cat masseter motoneurons before and during cholinergically induced motor atonia

Electrical stimulation of the nucleus pontis oralis during wakefulness enhances somatic reflex activity; identical stimuli during the motor atonia of active (rapid eye movement) sleep induces reflex suppression. This phenomenon, which is called reticular response-reversal, is based upon the generation of excitatory postsynaptic potential activity in motoneurons during wakefulness and inhibitory postsynaptic potential activity during the motor atonia of active sleep. In the present study, instead of utilizing artificial electrical stimulation to directly excite brainstem structures, we sought to examine the effects on motoneurons of activation of sensory pathways by exogenously applied stimuli (auditory) and by stimulation of a peripheral (sciatic) nerve. Accordingly, we examined the synaptic response of masseter motoneurons prior to and during cholinergically induced motor atonia in a pharmacological model of active sleep-specific motor atonia, the alpha-chloralose-anesthetized cat, to two different types of afferent input, one of which has been previously demonstrated to elicit excitatory motor responses during wakefulness. Following the pontine injection of carbachol, auditory stimuli (95 dB clicks) elicited a hyperpolarizing potential in masseter motoneurons. Similar responses were obtained upon stimulation of the sciatic nerve. Responses of this nature were never seen prior to the injection of carbachol. Thus, stimulation of two different afferent pathways (auditory and somatosensory) that produce excitatory motor responses during wakefulness instead, during motor atonia, results in the inhibition of masseter motoneurons. The switching of the net result of the synaptic response from one of potential motor excitation to primarily inhibition in response to the activation of sensory pathways was comparable to the phenomenon of reticular response-reversal. This is the first report to examine the synaptic mechanisms whereby exogenously or peripherally applied stimuli that elicit motor excitation during wakefulness instead elicit inhibitory motor responses during the motor atonia of active sleep. Thus, not only are motoneurons tonically inhibited during active sleep, but the selective elicitation of inhibitory motor responses indicates that this inhibition can be phasically increased in response to sensory stimuli, possibly in order to maintain the state of active sleep. The data provided the foundation for the hypothesis that, during naturally occurring active sleep, there is a change in the control of motor systems so that motor suppression occurs in response to stimuli that would otherwise, if present during other behavioral states, result in the facilitation of motor activity.     

The influence of temporal summation on a C-fibre reflex in the rat: effects of lesions in the rostral ventromedial medulla (RVM)

In intact rats, an inhibitory mechanism counteracts the increase in excitability of a flexor reflex seen in spinal animals following high-intensity, repetitive stimulation of C-fibres. We tested the hypothesis that the rostral ventromedial medulla (RVM) is involved in these processes. Electromyographic responses elicited by electrical stimulation of the sural nerve, were recorded from the ipsilateral biceps femoris in halothane-anaesthetised, sham-operated or RVM-lesioned rats. There were no significant differences between the C-fibre reflexes in the two groups in terms of their thresholds, latencies, durations or mean recruitment curves. The excitability of the C-fibre reflex was tested following 20 s of high-intensity homotopic electrical conditioning stimuli at 1 Hz. During the conditioning period, the EMG responses first increased in both groups (the wind-up phenomenon), but then decreased in the sham-operated rats and plateaued in the RVM-lesioned rats. These effects were followed by inhibitions that were very much smaller in the RVM-lesioned rats, both in terms of their magnitudes and their durations. It is concluded that the RVM is involved in inhibitory feedback mechanisms elicited by temporal summation of C-fibre afferents that both counteract the wind-up phenomenon and trigger long periods of inhibition.     

A systems analysis approach to medical error

Using decerebrate frogs (Rana catesbeiana), we investigated the role of vagal and laryngeal sensory feedback in controlling motor activation of the larynx. Vagal and laryngeal nerve afferents were activated by electrical stimulation of the intact vagal and laryngeal nerves. Pulmonary afferents were activated by lung inflation. Reflex responses were recorded by measuring efferent activity in the laryngeal branch of the vagus (Xl) and changes in glottal aperture. Two glottic closure reflexes were identified, one evoked by lung inflation or electrical stimulation of the main branch of the vagus (Xm), and the other by electrical stimulation of Xl. Lung inflation evoked a decrementing burst of Xl efferent activity and electrical stimulation of Xm resulted in a brief burst of Xl action potentials. Electrical stimulation of Xl evoked a triphasic mechanical response, an abrupt glottal constriction followed by glottal dilatation followed by a long-lasting glottal constriction. The first phase was inferred to be a direct (nonreflex) response to the stimulus, whereas the second and third represent reflex responses to the activation of laryngeal afferents. Intracellular recordings of membrane potential of vagal motoneurons of lung and nonlung types revealed EPSPs in both types of neurons evoked by stimulation of Xm or Xl, indicating activation of glottal dilator and constrictor motoneurons. In summary, we have identified two novel reflexes producing glottic closure, one stimulated by activation of pulmonary receptors and the other by laryngeal receptors. The former may be part of an inspiratory terminating reflex and the latter may represent an airway protective reflex.     

Electrical stimulation of the sciatic nerve alters neuropeptide content and lymphocyte migration in the subcutaneous tissue of the rat hind paw

To study the possible mechanism by which peripheral nerves mediate immune responses in target tissues, electrical stimulation of the sciatic nerve was combined with subcutaneous microdialysis of the hind paw. Following unilateral stimulation of the sciatic nerve, an ipsilateral rise in substance P and a bilateral rise in VIP levels were observed in dialysate samples from experimental vs control animals. Electrical stimulation of the sciatic nerve induced a marked hyperemia and swelling of the ipsilateral paw. Quantitative immunocytochemical analysis of paraffin-embedded sections of the hind foot pads demonstrated T lymphocyte migration ipsilateral to the stimulated nerve. These findings suggest that peripheral nerves can directly modulate local immune and inflammatory responses.     

Neuronal gagging activity patterns may be generated by neurons in the reticular area dorsomedial to the retrofacial nucleus in dogs

Expulsion is induced when hypercapnea and hypoxia develop during retching, or when the oropharyngeal mucosa is irritated (the gag reflex). The central pattern generator (CPG) for expulsion has been suggested to coexist with the CPG for retching in the reticular area dorsomedial to the retrofacial nucleus, which may correspond to the Botzinger complex (BOT). However, its participation in gagging induced by oropharyngeal irritation is unclear. To elucidate such participation, the firing patterns of BOT neurons were observed during gagging induced by stimulation of superior laryngeal afferents in decerebrate, paralyzed dogs. Only 23% of inspiratory and 34% of expiratory BOT neurons increased their firing in response to stimulation of the superior laryngeal nerve. In contrast, 75% of nonrespiratory BOT neurons showed enhanced firing with this stimulation. During gagging, each nonrespiratory, inspiratory, and expiratory BOT neuron fired with the same pattern that they exhibited during expulsion caused by changes in blood gases. These firing patterns could be classified into five types and are thought to be appropriate for generating neuronal gagging activity. These results suggest that the CPG for expulsion in the BOT produces gagging when it is activated by oropharyngolaryngeal afferents.     

Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat

Long-term potentiation (LTP) of spinal C-fibre-evoked field potentials can be induced by brief electrical stimulation of afferent C-fibres, by natural noxious stimulation of skin or by acute nerve injury. Here, we report that in urethane anaesthetized, adult rats prolonged high frequency burst stimulation of the sciatic nerve at Adelta-fibre strength produced long-term depression (LTD) of C-fibre-evoked field potentials, and also depressed the increased amplitudes of C-fibre-evoked field potentials recorded after LTP had been established (depotentiation). Electrical stimulation of Abeta-fibres failed to induce LTD or depotentiation. In spinalized rats, prolonged Adelta-fibre conditioning stimulation induced LTP rather than LTD of C-fibre-evoked field potentials. Thus, tonic descending inhibition may determine the direction of plastic changes in C-fibre-mediated synaptic transmission. Spinal application of the N-methyl-D-aspartic acid receptor antagonist D-APV blocked induction of LTD in intact rats and LTP in spinalized rats. The presently described LTD and the depotentiation of established LTP of C-fibre-evoked field potentials in spinal dorsal horn may underlie some forms of prolonged analgesia induced by peripheral nerve stimulation procedures.     

Reflex relationships between the cervical esophagus and the respiratory system in cats

The present study focused on reflex relationships between the esophagus and the respiratory system in cats, namely the changes in airway tone and pulmonary circulation elicited by mechanical or acid (pH 2) stimulation of esophageal afferents. One-minute of sustained distension of the cervical esophagus increased tracheal pressure (PTr), decreased pulmonary artery pressure (PPA) and to a higher extent pulmonary blood flow (QPA) and lowered arterial blood pressure (Pa). This was associated with significant variations in arterial blood gases (increased PaO2 and decreased PaCO2). Acid stimulation of the cervical esophagus caused a marked increase in PTr and a modest fall in QPA. In both circumstances, cervical bivagotomy abolished PTr changes, whereas the changes in pulmonary hemodynamics but not in Pa were then accentuated. Further cervical sympathectomy suppressed the vascular response. These observations show the existence of reflex influences of esophageal afferents on the control of airway tone and pulmonary vascular resistance. The vagus nerve is the efferent arm of the bronchomotor reflex whereas modulation of the sympathetic control of pulmonary circulation seems to be responsible for the changes in pulmonary hemodynamics.     

Reversal of fusimotor reflex responses during locomotion in the decerebrate cat

The effect of brief trains of electrical stimulation, at 2, 3 and 20 x threshold (T), of cutaneous afferents in the medial plantar nerve on the discharges of single medial gastrocnemius static and dynamic gamma-efferents has been investigated at rest and during locomotion in a decerebrate cat preparation. The units were classified as dynamic (10 units) or static (10 units) indirectly on the basis of their resting and locomotor discharge characteristics. Responses were assessed by calculating the change in mean gamma-rate during the 100 ms after stimulus onset compared with a control period. At rest, most dynamic neurones were inhibited by stimulation at 2T (9 of 10 units) and above. In contrast, the resting responses of most static neurones were excitatory at 2T (9 of 10 units) and 3T, while 20T produced static gamma-effects that varied in sign. During locomotion the responses of both types of gamma-efferent were phase related. Two patterns were observed with dynamic units. For seven dynamic neurones, at stimulus levels of 2T (7 units) and above, responses during electromyogram (EMG) bursts were inhibitory while those between bursts were not significantly different from zero. However, for three other dynamic units, a phase-related reversal of reflex responses was observed at some stimulus intensities (always 2T, 3 units) comprising inhibition during, and excitation between, EMG bursts. For static neurones, inhibitory (never excitatory) responses occurred during walking at stimulus intensities of 2T (10 units) and above. The locomotor responses of static units were maximum during (3 units) or between (7 units) EMG bursts and were minimum in the opposite phase of EMG activity. A task-related reversal of reflex responses was thus generally apparent (9 of 10 units) to low intensity stimulation (2T) for static gamma-efferents during locomotion (inhibition) compared with rest (excitation). During locomotion there was a significant linear relation between the magnitude of response and the background gamma-rate for static units and those dynamic units that did not exhibit phase-related reflex reversal (total, 17 units). For dynamic gamma-efferents, inhibition at rest and during locomotion occurred at short (spinal) latencies which were not significantly different and are consistent with the involvement of the same interneuronal pathway. We conclude that pathways of opposite sign may dominate the responses of fusimotor neurones to low threshold cutaneous afferents from the plantar surface of the foot depending on behavioural context. Furthermore, the cutaneous reflex responses of both types of gamma-motoneurones during locomotion appear to vary with the source of the afferent input and do not constitute a general excitatory drive. The results are discussed in relation to the role and reflex control of the fusimotor system.     

Release of somatostatin and its role in the mediation of the anti-inflammatory effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve

1. The effect of antidromic stimulation of the sensory fibres of the sciatic nerve on inflammatory plasma extravasation in various tissues and on cutaneous vasodilatation elicited in distant parts of the body was investigated in rats pretreated with guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). 2. Antidromic sciatic nerve stimulation with C-fibre strength (20 V, 0.5 ms) at 5 Hz for 5 min elicited neurogenic inflammation in the innervated area and inhibited by 50.3 +/- 4.67% the development of a subsequent plasma extravasation in response to similar stimulation of the contralateral sciatic nerve. Stimulation at 0.5 Hz for 1 h also evoked local plasma extravasation and inhibited the carrageenin-induced (1%, 100 microl s.c.) cutaneous inflammation by 38.5 +/- 10.0% in the contralateral paw. Excitation at 0.1 Hz for 4 h elicited no local plasma extravasation in the stimulated hindleg but still reduced the carrageenin-induced oedema by 52.1 +/- 9.7% in the paw on the contralateral side. 3. Plasma extravasation in the knee joint in response to carrageenin (2%, 200 microl intra-articular injection) was diminished by 46.1 +/- 12.69% and 40.9 +/- 4.93% when the sciatic nerve was stimulated in the contralateral leg at 0.5 Hz for 1 h or 0.1 Hz for 4 h, respectively. 4. Stimulation of the peripheral stump of the left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extravasation in the trachea, oesophagus and mediastinal connective tissue in rats pretreated with atropine (2 mg kg(-1), i.v.), guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). These responses were inhibited by 37.8 +/- 5.1%, 49.7 +/- 9.9% and 37.6 +/- 4.2%, respectively by antidromic sciatic nerve excitation (5 Hz, 5 min) applied 5 min earlier. 5. Pretreatment with polyclonal somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the anti-inflammatory effect of sciatic nerve stimulation (5 Hz, 5 min) on a subsequent neurogenic plasma extravasation of the contralateral paw skin. The inhibitory effect of antidromic sciatic nerve excitation on plasma extravasation in response to vagal nerve stimulation was also prevented by somatostatin antiserum pretreatment. 6. Cutaneous blood flow assessment by laser Doppler flowmetry indicated that antidromic vasodilatation induced by sciatic nerve stimulation was not inhibited by excitation of the sciatic nerve of the contralateral leg (1 Hz, 30 min) or by somatostatin (10 microg/rat, i.v.) injection. 7. Plasma levels of somatostatin increased more than 4 fold after stimulation of both sciatic nerves (5 Hz, 5 min) but the stimulus-evoked increase was not observed in cysteamine (280 mg kg(-1), s.c.) pretreated rats. 8. These results suggest that somatostatin released from the activated sensory nerve terminals mediates the systemic anti-inflammatory effect evoked by stimulating the peripheral stump of the sciatic nerve.     

Impaired modulation of sympathetic excitability by nitric oxide after long-term administration of organic nitrates in pigs

BACKGROUND: Endogenous nitric oxide (NO) reduces sympathetic vasoconstriction by attenuating neuronal excitability in the brain stem and inhibition of postganglionic neurotransmission. We studied whether this modulation of sympathetic circulatory control by NO may be altered during chronic administration of NO donor drugs in pigs. METHODS AND RESULTS: Nitrate tolerance was induced by oral administration of isosorbide dinitrate (ISDN, 4 mg/kg per day for 4 weeks) in eight pigs. Four of them were chronically instrumented for the measurement of mean arterial blood pressure and cardiac output in the conscious state. ISDN treatment caused hemodynamic tolerance to NO donors and significantly increased the hypotensive responses to pharmacologic ganglionic blockade in conscious pigs. In general anesthesia, ISDN-treated animals and age-matched controls (n=5) had similar baseline renal sympathetic nerve activity and in both groups neither inhibition of NO synthases (NOS) nor administration of NO donors to the brain stem by intracerebroventricular (i.c.v.) infusions caused significant changes in baseline renal sympathetic nerve activity. However, whereas sympathoexcitatory responses to glutamate (0.5 mL, 0.1 mol/L, i.c.v.) or electrical stimulation of somatic nerve afferents were significantly potentiated by central NOS inhibition and attenuated by NO donors in controls, these treatments no longer had significant effects in ISDN-treated pigs. Furthermore, reflex sympathetic activation in response to intravenous NO donor treatment was more pronounced in nitrate tolerant animals, which suggests loss of central sympathoinhibitory effects of NO. Subsequent histology on brain stem slices with NADPH-diaphorase as NOS marker revealed significant reduction of NOS density in ISDN-treated pigs. CONCLUSIONS: Long-term administration of organic nitrates reduces the number of NO-producing neurons in the brain stem and causes loss of inhibitory effects of NO on sympathetic excitability. This component of tolerance to organic nitrates may be important in patients confronted frequently with sympathetic activation caused by mental and/or physical stressors.     

Activity staining of protein inhibitors of proteases on gelatin-containing polyacrylamide gel electrophoresis

Stimulation of the supraorbital branch of the trigeminal nerve (SO) elicited eye blinks in the rabbit, but did not decrease the amplitude of visual cortical evoked potential from stimulation of the optic chiasm (OX). In addition, the SO stimulation neither induced an inhibitory postsynaptic potential (IPSP) in LGN cells, nor activated inhibitory interneurons in the thalamic reticular nucleus (TRN), which proved to mediate both recurrent inhibition and saccadic suppression in the dorsal lateral geniculate nucleus (LGN). All these indicate that there is no visual suppression in the rabbit LGN during blink reflex.     

Functional changes of brainstem reflexes in Parkinson's disease. Conditioning of the blink reflex R2 component by paired and index finger stimulation

Recovery curves of the R2 component of the blink reflex have been studied in 10 control subjects and 13 parkinsonian patients both after ipsilateral paired stimulation of the supraorbital nerve and after index finger stimulation. In control subjects, both types of conditioning induced a comparable marked inhibition lasting more than 600 ms. In parkinsonian patients, inhibition was reduced after both conditionings. However, differences appeared in the magnitude of the changes: after paired stimulation, it was less significant (ANOVA and post-hoc Duncan's test: p = 0.04) than after index finger stimulation (p = 0.002). In that latter situation, the more marked reduction in inhibition is interpreted, in the light of current physiologic knowledge, by hypoactivity of the Nucleus Reticularis Giganto Cellularis (NRGC) which would make less efficient inhibitory interneurones in the trigemino-facial pathway. The results are thus compatible with the suggestion that NRGC is made indirectly less active in Parkinson's disease.     

GTP analogs suppress uptake but not transport of D-glucose analogs in Glut1 glucose transporter-expressing Xenopus oocytes

The effect of electrical stimulation of the ventroposterolateral (VPL) thalamic nucleus on mechanical allodynia in the unrestrained awake rat was investigated. In 7 rats, a monopolar stimulation and recording electrode was implanted in the VPL thalamic representation area of the hindpaw. Exact target localisation was performed by means of thalamic evoked potentials induced by stimulating the contralateral tibial nerve. A peripheral mononeuropathy was induced by partly ligating the right sciatic nerve. Sensitivity of the hindpaws to mechanical stimulation was assessed with a set of von Frey hairs. One to 4 weeks after nerve ligation, all rats showed allodynia to mechanical stimulation and signs of spontaneous pain. Electrical stimulation of the contralateral VPL thalamic nucleus abolished the mechanical allodynia observed at the nerve ligated side. The effect of VPL stimulation outlasted the stimulation period by 15 min. No effect on the withdrawal thresholds at the control (sham operated) side was observed. These animals data support the clinical reports that stimulation of the sensory thalamus may alleviate pain of neuropathic origin.