Reduced spinal reflexes following intrathecal baclofen in the rabbit

Summary Intrathecal baclofen is effective in reducing polysynaptic spinal reflexes in awake rabbits. A single lumbar infusion of 2.5–5.0 ng drug caused a significant reduction in the crossed extensor response to electrical stimulation of the plantar surface of the hindlimb. This inhibition lasted 5 h or more. At doses of 3 or less, the forelimbs were unaffected.     

Enhanced trigemino-cervical-spinal reflex recovery cycle in pain-free migraineurs

OBJECTIVE: To evaluate trigemino-cervical-spinal reflexes (TCSRs) in a group of migraine patients during the pain-free period. BACKGROUND: TCRSs are part of a complex nocifensive response involving the cervical and the upper limb muscles, and are modulated by supraspinal inhibitory pathways; it may, thus, be possible to use TCRSs to explore the trigeminal system in migraineurs. METHODS: A total of 43 migraine patients without aura (MWoA, 32 patients) or with typical aura (MWA, 11 patients) and 30 age- and sex-matched healthy subjects took part in the study. TCRSs were obtained by stimulating the supraorbital nerve and recorded from the semispinalis capitis muscle and the biceps brachii. The latency (L, msec), area (A, mVms) and recovery cycle of the reflexes were recorded. The effects of heterotopic painful stimulation on the neurophysiological parameters were studied by a validated cold pressor test (CPT). RESULTS: No significant changes were found between either migraine patients and controls or MWoA and MWA patients in the mean values in the L and A of TCRSs (t-test, P > .05). The recovery curve of the trigemino-cervical reflexes (TCRs) was significantly faster in migraine patients than in controls, while no differences were found in the trigemino-spinal reflexes (TSRs) (t-test, P < .01). Activation of the diffuse inhibitory controls through the CPT induced a significant reduction in the TCRs and TSRs area in both migraine patients and controls (paired t-test, P < .01), though the extent of this reduction did not differ significantly between migraineurs and controls (t-test, P > .05). COMMENTS: Our data suggest that the pain-free period in migraine patients is characterized by a hyperexcitability of the trigeminal pathways and of their anatomical and functional connections with the upper cervical cord neurons, and that this abnormal hyperexcitability does not appear to be due to a lack of a supraspinal inhibitory modulation.     

System identification of human stretch reflex dynamics: Tibialis anterior

Summary System identification methods have shown that the stretch reflex in the human ankle extensor (triceps surae, TS) may be modeled as velocity feedback via a single, short latency pathway containing a uni-directional rate-sensitive nonlinearity. Evidence of differences in the reflex organization in flexors and extensors led us to use the same methods to examine stretch reflexes in the ankle flexor (tibialis anterior, TA). Five normal subjects maintained a tonic contraction of TA while subjected to repeated, stochastic perturbations of ankle position. Position, torque, and smoothed, rectified EMGs from TA and TS were recorded and ensemble averaged over 25 stimulus presentations. Linear impulse response functions relating TA EMG to ankle velocity were then determined. The results confirmed the existence of significant differences between stretch reflexes in TA and TS. In particular: 1. TA impulse response functions were characterized by two distinct peaks of excitation separated by a period of inhibition. The impulse response function amplitude increased with increasing mean torque and decreased with displacement amplitude although the sensitivity of the two peaks to these changes was different. This was interpreted as suggesting that TA stretch reflexes involve two separate pathways both involving muscle spindle information. 2. TA stretch reflexes modulate tonic activity much less than do those in TS. 3. The strong uni-directional rate-sensitive nonlinearity seen in TS was not present in TA. The functional significance of these differences remains to be determined.     

Effects of dorsal cord stimulation on stretch reflexes

The effects of dorsal cord stimulation on phasic and tonic stretch reflex activity in extensor muscles were studied in decerebrate cats. The tonic stretch response was depressed in both fore- and hindlimb (stimulation at levels C1 and T8, respectively) and this often persisted for 5–20 min after the end of 1–10 min of dorsal cord stimulation. Depression of the phasic stretch response was only consistently seen in the forelimb during stimulation (C1) and this rarely outlasted the period of stimulation. These results support the idea that dorsal cord stimulation can reduce muscle tone but provide no explanation for the long-lasting effects of chronic, continuous stimulation in spastic man.     

Central cholinergic interactions in somato-vegetative reflexes

In cats lightly anaesthetized with urethane (600 mg/kg, i.p.), electrical stimulation of the sciatic nerve elicited frequency-dependent pressor reflexes and contractions of the nictitating membrane. Administration of oxotremorine (0.2 mg/kg, i.v.) or physostigmine (0.5 mg/kg, i.p.) resulted in depression of the pressor reflexes. At the same time, physostigmine enhanced the reflex contractions of the nictitating membrane, while oxotremorine induced sustained contraction of the latter. All these effects were antagonized by the tertiary amine scopolamine, but not by the quaternary atropine methylbromi.The results point to a role of central cholinergic mechanisms in the integration of somato-vegetative reflexes, and give evidence that the sympathetic driving of different effectors is not uniformly organized by the central nervous system.     

Serotonergic fiber sprouting to external anal sphincter motoneurons after spinal cord contusion

The present study analyzed the anatomical plasticity of serotonergic immunoreactive projections to external anal sphincter (EAS) motoneurons, and the behavioral plasticity of EAS reflexes, penile erection, and locomotion in rats with spinal contusion injury (SCI) or complete spinal cord transection (TX). Electromyographic activity of the EAS, penile erection latency, and BBB locomotor score exhibited parallel recovery over the 6-week recovery period after contusion SCI. This pattern of recovery was not observed in TX animals. While locomotor scores demonstrated a small increase after TX, erectile and anorectal function remained at abnormal levels established immediately after injury. Serotonergic immunofluorescent (5-HT-IF) staining at the lesion site identified a small number of fibers spared after SCI that may provide a substrate for functional recovery. Pixel density measurements of 5-HT-IF in the vicinity of retrogradely labeled EAS and unlabeled pudendal motoneurons necessary for penile erection provide indirect evidence of serotonergic sprouting that parallels the observed functional recovery in animals with SCI. No 5-HT-IF was detected caudal to the injury site in TX animals. These studies indicate: (1) lumbosacral eliminative and reproductive reflexes provide a valid means of studying the mechanisms of post-SCI plasticity; (2) the similar recovery curves suggest similar return of descending control, perhaps through sprouting of descending serotonergic fibers; (3) the observed deficits after TX likely represent the permanent removal of descending inhibition and reflect reorganization of segmental circuitry.     

Autonomic reflexes in heterotopic heart transplantation

Heterotopic heart transplantation (HHT) is useful in the setting of irreversible pulmonary hypertension or donor/recipient size mismatch. The resulting pump is composed of two hearts attached to one another. Autonomic tone can be lost in orthotopic heart transplantation, but HHT is unique in that the donor heart lacks an autonomic nervous supply. This is relevant in terms of increasing cardiac output for example during exercise. We document altered autonomic tone in two of our patients who underwent HHT, and discuss the bearing this has on cardiac function.     

Multiple levels of sensory integration in the intrinsic sensory neurons of the enteric nervous system

1. The enteric nervous system (ENS) is present in the wall of the gastrointestinal tract and contains all the functional classes of neuron required for complete reflex arcs. One of the most important and intriguing classes of neuron is that responsive to sensory stimuli: sensory neurons with cell bodies intrinsic to the ENS. 2. These neurons have three outstanding and interrelated features: (i) reciprocal connections with each other; (ii) a slow excitatory post-synaptic potential (EPSP) resulting from high-speed firing in other sensory neurons; and (iii) a large after-hyperpolarizing potential (AHP) at the soma. Slow EPSP depolarize the cell body, generate action potentials (APs) and reduce the AHP. Conversely, the AHP limits the firing rate and, hence, reduces transmission of slow EPSP. 3. Processing of sensory information starts at the input terminals as different patterns of APs depending on the sensory modality and recent sensory history. At the soma, the ability to fire APs and, hence, drive outputs is also strongly determined by the recent firing history of the neuron (through the AHP) and network activity (through the slow EPSP). Positive feedback within the population of intrinsic sensory neurons means that the network is able to drive outputs well beyond the duration of the stimuli that triggered them. 4. Thus, sensory input and subsequent reflex generation are integrated over several hierarchical levels within the network on intrinsic sensory neurons.     

AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain

INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by ACE inhibitors has been demonstrated to reduce total mortality in cardiovascular diseases. This advantage was attributed in part to changes of autonomic cardiovascular control, exemplified by an increase of heart rate variability (HRV) and baroreflex gain (BRG). We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG. MATERIALS AND METHODS: In a double-blind randomized cross-over design 25 young males took eprosartan (600 mg/day) and placebo each for a period of 7 days with a wash-out period of at least 4 weeks in between. At the end of the intake phases simultaneous recordings of arterial blood pressure (AP; Finapres) and electrocardiogram (ECG) were taken. Power spectra of HRV and arterial blood pressure variability (APV) were calculated by fast Fourier transform (FFT) and served to calculate BRG. Ang-II levels were measured by radioimmunoassay. RESULTS: Eprosartan tended to lower mean AP, it slightly increased heart rate (HR) (p<0.05), and markedly increased circulating Ang-II levels (p<0.01). Eprosartan diminished the total power of HRV (p<0.05) and the BRG (p<0.01). The low/high frequency (LF/HF) ratio of HRV and the APV were not altered. CONCLUSIONS: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. We speculate that these findings are due to the marked increase in circulating angiotensin II (Ang II). Further studies are needed to clarify whether angiotensin type 1 (AT1) blockers with potential actions inside the blood-brain barrier (BBB) may have different effects on HRV and BRG.     

Baroreceptor-sensitive neurons in the rat paratrigeminal nucleus

The paratrigeminal nucleus (Pa5) is a small collection of medullary neurons localized in the dorsal lateral spinal trigeminal tract. Electrophysiological and anatomical studies showed functional Pa5 efferent connections to the rostroventrolateral reticular nucleus (RVL) and the nucleus of the solitary tract (NTS), both well-studied components of the baroreflex arch. Similarly to the NTS, the main site for termination of cardiovascular peripheral afferents, the Pa5 receives primary sensory inputs of glossopharyngeal and vagus nerves, which suggests that the Pa5 may play a role in the baroreceptor reflex modulation. Simultaneous recording from multiple single neurons in 10 freely behaving rats showed that 37% of recorded Pa5 neurons altered firing rates (35% increased and 2% decreased) during the peak arterial blood pressure response to i.v. phenylephrine. Forty two percent of the 84 identified Pa5 baroreceptor-excited neurons showed high correlation to cardiac cycle denoting the synchronous phasicity to fast changes of blood pressure. Autocorrelation analysis revealed that 48 pressure-sensitive and 55 nonpressure-sensitive neurons have periodical activities which were not directly linked to cardiac cycle. We suggest that the Pa5, a yet unknown component of the baroreflex pathway, may relay baroreceptor information to the NTS and by passing other components of the baroreceptor reflex arch, directly to sympathetic premotor neurons in the RVL.