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Development and maturation of postural reflexes in normal kittens.

In order to evaluate neurologic development, postural reflexes were tested in normal kittens from birth through 7 weeks of age until stable adult patterns of performance were attained. These reflex tests included: body and air righting, visual placing, chin placing, tactile placing, hopping, and locomotion. A protocol for scoring responses was designed for each individual reflex to differentiate their progression. The first reflexes to mature were visual placing, chin placing, and body righting which attained a maximal score during the 3rd week of life. This was followed by maturation of the forelimb hopping reflex and independent locomotion during the 4th week. Forelimb tactile placing responses, hind limb hopping reflexes, and air righting developed by the 5th week. Hind limb tactile placing responses were the last to mature. They became fully expressed in the 6th week. The pattern of ontogeny of these reflexes proceeded in a cephalocaudal direction. This is in agreement with earlier observations of others who correlated the maturation of reflex responses in kittens with myelination in the central nervous system.

Aging↗

Effect of inhibitory amino acid antagonists on masseteric reflex suppression during active sleep.

We examined the pharmacological basis for the suppression of the masseteric (jaw-closer) reflex which occurs during the behavioral state of active sleep. Accordingly, the masseteric reflex was recorded in intact, unanesthetized, normally respiring cats during naturally occurring states of wakefulness and active sleep. The amplitude of the reflex during these states was determined before and after strychnine, picrotoxin, and bicuculline methiodide were applied, by microinjection, to the trigeminal motor nucleus. The effectiveness of each drug in blocking the active sleep-related suppression of the masseteric reflex was examined and compared with the degree of suppression evoked, during wakefulness, by stimulation of the inferior alveolar nerve. Microinjection of strychnine (50 microM to 20 mM) reduced the degree of suppression of the masseteric reflex during active sleep, but was markedly more effective in blocking reflex suppression that was induced by stimulating the inferior alveolar nerve. Picrotoxin and bicuculline methiodide (10 microM to 5 mM) produced a nonspecific increase in the amplitude of the masseteric reflex during both states. Thus, these substances did not appear to reduce the degree of reflex suppression induced by inferior alveolar nerve stimulation or that occurring spontaneously during active sleep. We concluded that strychnine-sensitive postsynaptic inhibition does participate in the suppression of masseter motor activity during active sleep, but that it is not the exclusive factor responsible for atonia of the masseter musculature during this state.

Amino Acids↗

Tizanidine-induced depression of polysynaptic cutaneous reflexes in nonanesthetized monkeys is mediated by an alpha 2-adrenergic mechanism.

Previous studies in anesthetized or reduced preparations of nonprimate animals revealed that the alpha 2-adrenergic agonist tizanidine, clinically used as an antispastic drug, effectively reduces polysynaptic flexor reflexes. To further clarify the invoked adrenergic mechanism for physiological motor functions, and in view of the clinical relevance of tizanidine, the effect of this substance was reinvestigated in awake, nonanesthetized monkeys. Systemic applications of tizanidine dose-dependently reduced the magnitude of the electromyographic response of the flexor reflex that was induced by nonnoxious stimulation of cutaneous afferents. Whereas the effects on the flexor response were consistent, the changes of the background electromyogram were much more variable, often not paralleling those of the reflex. The reflex depression produced by tizanidine could be prevented by pretreatment with the alpha 2-antagonist yohimbine. It is concluded that the action of tizanidine on spinal reflexes, and therefore probably also on hyperactive reflexes of spastic patients, is mediated via the alpha 2-adrenergic properties of the drug. On the basis of the present results, taken together with previous observations that tizanidine transiently inactivates neurons of the nucleus locus coeruleus, it is proposed that the reflex depression may be caused by a removal of a descending noradrenergic facilitation exerted on spinal reflex transmission. This interpretation leaves open further possible actions of tizanidine exerted directly on spinal interneurons.

Adrenergic alpha-Antagonists↗

An intrinsic neural pathway for long intestino-intestinal inhibitory reflexes.

We studied the mechanisms of initiation and pathways for the propagation of intestino-intestinal inhibitory reflexes induced by close intraarterial injections of neostigmine in conscious dogs. Two or three T-shaped catheters were surgically implanted in the intestinal branches of the superior mesenteric artery to inject pharmacologic agents locally in 10-15-cm-long segments. Migrating myoelectric complexes were recorded by a set of 10 electrodes and strain-gauge transducers. Close intraarterial injection of neostigmine initiated strong contractions of long duration in the perfused segment that terminated phase III activity in progress 90-150 cm distal or proximal to the cannulated sites and stopped its further migration. Atropine or 4-diphenylmethoxy-N-methylpiperidine methiodide injected just before neostigmine administration through the same catheter blocked both the local contractile effects and the reflex inhibition of phase III activity. Pirenzepine or hexamethonium injected in a similar manner did not affect the local response to neostigmine but blocked the reflex inhibition of phase III activity. A transection and reanastomosis in the mid-small intestine blocked the reflex inhibition by close intraarterial injection of neostigmine beyond the transection site. Pirenzepine, atropine, or hexamethonium injected through a middle catheter also blocked the reflex inhibition of phase III activity beyond the site perfused with these cholinergic antagonists. Close intraarterial administration of 4-diphenylmethoxy-N-methylpiperidine methiodide at a middle site had no effect on reflex inhibition. We concluded that strong spasmodic contractions in the small intestine initiate an intestino-intestinal inhibitory reflex in both directions. This reflex is mediated through an intrinsic neural pathway involving nicotinic and M1 muscarinic receptors.

Animals↗

Long-lasting modification of reflexes after neonatal nerve injury in the rat.

The reflex activity of motoneurones to the extensor digitorum longus (EDL) muscle following sciatic nerve crush during the first 5 days after birth (neonatal crush) or in the adult (adult crush) was studied 3-6 months later, when the axons had reinnervated their target muscles. Electromyograms (EMG) and muscle tension were recorded from the EDL muscle (a physiological flexor) on the injured and uninjured sides. Reflex responses were evoked by stimulation of the common peroneal (CP), the tibial (T) and the sural (S) nerves, ipsilateral and contralateral to the side of injury. In animals which had sustained a neonatal crush, stimulation of branches of the injured sciatic nerve elicited ipsilateral reflex responses that were about 3 times larger than those recorded from the uninjured side or in normal animals. Stimulation of the CP nerve on the uninjured side invariably elicited a contralateral reflex response from the reinnervated muscles, while stimulation of the CP nerve on the injured side either failed to produce a response or produced a very weak reflex response from the control muscles. Reflexes recorded from the reinnervated muscles by stimulation of the tibial and sural branches of the uninjured sciatic nerve were 3-7 times greater than those recorded from the uninjured side or in normal animals. The reflex responses obtained from reinnervated muscles of animals with nerve injury in adulthood were similar to those obtained from control, unoperated adult rats. These results indicate that sciatic nerve injury during a critical development period leads to a permanent enhancement of reflex responses from reinnervated fast flexor muscles not seen after similar injury in adults.

Adaptation, Physiological↗

Proximally evoked soleus H reflexes in the evaluation of axonal neuropathy.

It is sometimes difficult to differentiate physiologically distal axonopathy from proximal root or nerve disease. Standard soleus H reflexes evoked by distal tibial nerve stimulation at the popliteal fossa are often absent in both syndromes. In this study we distinguish the two by the presence or absence of soleus H reflexes evoked by proximal sciatic nerve stimulation at the gluteal fold. In 12 normal subjects maximum H reflex amplitudes evoked by distal tibial and proximal sciatic stimulation were essentially equal. In 12 patients with suspected distal polyneuropathy, proximal but not distal stimulation evoked H reflexes. By contrast, in 10 patients with lumbosacral root or proximal nerve disease, both proximal and distal stimulation failed to elicit H reflexes. In 2 patients with lower motor neuronopathy, low but comparable amplitude H reflexes were evoked at both sites. We conclude that the presence of a proximally evoked soleus H reflex may provide specific evidence of distal axonopathy when standard soleus H reflexes are absent.

Adult↗

Cyclobenzaprine: effect on tonic vibration reflexes in local tetanus cat preparations.

Local tetanus was induced by the injection of toxin into the gastrocnemius-soleus muscle of cats. After 48 hr, longitudinal vibration of the muscle was used to elicit a reflex contraction (tonic vibration reflex, TVR). In other experiments, electrical stimulation of various regions of the central nervous system served to elicit contraction of the muscle alone or to facilitate a vibration (150 mu at 300 Hz)-induced tonic vibration reflex. In contrast with normal animals, tonic vibration reflex responses in local tetanus preparations of decerebrate cats were augmented after transection of the spinal cord at Cl. In decerebrate local tetanus preparations, a dose-related reduction of tonic vibration reflex responses, induced at all frequencies and amplitudes of muscle vibration, was observed after doses of 0.5 to 3.5 mg/kg (i.v.) of cyclobenzaprine. Muscle contractions induced by stimulation of the medial reticular formation and facilitation of tonic vibration reflex responses were more sensitive to the action of cyclobenzaprine than were similar responses activated through stimulation of Deiters' lateral vestibular nucleus. In spinal preparations, tonic vibration reflex responses were only moderately reduced after similar doses of cyclobenzaprine. Contractions induced by stimulation of the spinal cord (T6) and facilitated tonic vibration reflex responses were only moderately reduced, whereas the post-stimulus-induced facilitations were considerably attenuated. Thus, experiments in local tetanus preparations support further the concept that the major site of action of cyclobenzaprine is supraspinal, whereas its action upon spinal structures contributes to its overall skeletal muscle-relaxant activity.

Amitriptyline↗

Selective serotonin1A/1B agonists differentially affect spinal nociceptive reflexes.

The purpose of the present experiments was to determine whether serotonin-1A (5-HT1A) and serotonin-1B (5-HT1B) binding sites, recently characterized in the spinal cord of the rat, mediate differential effects of 5-HT on spinal nociceptive processing. Several days after spinal transection at T10, rats were injected intraperitoneally at 20 min intervals, with increasing doses (0, 0.1, 0.4, 2.0, 9.0 mg/kg) of either a 5-HT1A selective agonist (8-OH-DPAT, buspirone) or a 5-HT1B agonist (mCPP, TFMPP). Nociceptive sensitivity was determined by quantifying, in cm2, changes from baseline in the receptive field areas of three spinal nociceptive withdrawal reflexes after noxious (greater than 400 mmHg) levels of mechanical stimulation. The 5-HT1A agonist 8-OH-DPAT and buspirone, significantly increased in a dose-dependent manner the receptive field areas of the three reflexes, with the following log ED50 values (nmol/kg): ventroflexion reflex--buspirone (2.75), 8-OH-DPAT (2.70); dorsiflexion reflex--buspirone (2.91), 8-OH-DPAT (2.67); lateral flexion reflex--buspirone (3.51), 8-OH-DPAT (2.77). The hypersensitivity of the reflexes after pretreatment with buspirone was effectively blocked by the 5-HT1A selective antagonist spiperone, at all doses (0.001, 0.01, 0.1 and 1.0 mg/kg) tested. The 5-HT1B selective agonists mCPP and TFMPP significantly decreased the receptive field are of the ventroflexion reflex (log ED50 values: mCPP, 3.79 nmol/kg; TFMPP, 3.61 nmol/kg) with no significant effect on the dorsiflexion or lateral flexion reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of nitric oxide in spinal nociceptive reflexes in rats with neurogenic and non-neurogenic peripheral inflammation.

This in vivo electrophysiological study concerns the role of nitric oxide (NO) in mechanical and thermal spinal nociceptive reflexes in alpha-chloralose anaesthetized rats. The effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 5-40 mg/kg i.v.) on reflexes were compared both in normal rats and in those with peripheral inflammation induced neurogenically (mustard oil) and non-neurogenically (carrageenan). Methoxamine (0.1 mg/kg i.v.) was used to mimic the marked hypertension caused by L-NAME. Thermal nociceptive reflexes were equally reduced by methoxamine and L-NAME in both normal and inflamed rats, implying that NO has no role in mediating thermal reflexes. However, L- (but not D-) NAME dose dependently and significantly inhibited mechanical reflexes in both carrageenan inflamed (to 37 +/- 12% control) and mustard oil inflamed rats (to 75 +/- 8% control). Moreover, these reductions were greater than those by methoxamine. In contrast, L-NAME did not reduce mechanical reflexes in rats with no inflammation or in spinalized rats with inflammation. The inhibition of mechanical reflexes with L-NAME in carrageenan inflamed rats was reversed and prevented by pre- or post-treatment with L- (but not D-) arginine (50-200 mg/kg i.v.). These data imply a supraspinal role for NO in mediating mechanical (but not thermal) nociceptive reflexes only in those rats with peripheral inflammation.

Amino Acid Oxidoreductases↗

Blockade of 'alveolar' and airway reflexes by local anesthetic aerosol in dogs.

To determine whether local anesthetic aerosol could selectively block a reflex thought to originate from the alveoli, two small particle bupivacaine aerosols (mass median diameters 1.0 and 1.7 micron) were administered on separate occasions to spontaneously breathing anesthetized dogs. Both aerosols resulted in a small but statistically significant increase in VT and one produced an increase in f. The pulmonary chemoreflex to right heart injection of capsaicin, the cough reflex and the Hering-Breuer inflation reflex were unaffected. The ability of a large particle aerosol (mass median diameter 4.8 micron) to block these reflexes was also assessed. This aerosol produced a progressive slowing and deepening of breathing which was maximal after 20 min of aerosol inhalation. Ten min of this aerosol attenuated the pulmonary chemoreflex and abolished the cough and inflation reflexes; 20 min abolished all reflexes. These had recovered by about 1 h after aerosol. Intravenous bupivacaine had no effect on breathing or any reflex. We conclude that a local anesthetic aerosol can block reflexes arising from the alveoli, but not selectively.

Aerosols↗

Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats.

Respiratory effects of electrical stimulation of the upper airways (UAW) before and during apnoeic episodes induced by nitrogen inhalation were studied in 9 anaesthetized cats. In eupnoeic animals these electrically-evoked reflexes comprise rapid and powerful inspiratory efforts characterized by strong maximal airway occlusion pressures (Pmax = 635 +/- 39 mm H2O) and rapid peak inspiratory flow rates (PIF = 536 +/- 36 ml.sec-1) similar to the sniff-like aspiration reflex elicited mechanically. Electrical stimulation of the UAW mucosa can elicit reflex inspirations and sniff-like aspiration reflexes even during reversible hypoxic apnoea but their intensity and reproducibility are transiently reduced. When repeated adequately, the electrically-induced reflexes can increase the reactivity of respiratory centre and interrupt or terminate apnoeic episodes as do other types of UAW stimulation. Reflex mechanisms and respiratory centre activations seem to be involved in these effects. The results suggest that electrical stimulation of UAW could be useful for testing the respiratory centre reactivity as well as for reflex reversal of apnoeic episodes and restoration of normal breathing in animal experiments and clinico-physiological studies. Such investigation of the role of UAW reflexes in the pathogenesis and therapy of apnoeic syndromes might also be possible by using a cardiostimulator adapted as respiratory pacemaker.

Animals↗

A technique for measuring the mechanical actions of heterogenic (intermuscular) reflexes in the decerebrate cat.

Two muscle pullers were used to study the natural mechanical actions of autogenic reflexes, which arise from muscle receptors and feed back to the muscle of origin, and heterogenic reflexes, which feed back to muscles other than the muscle of origin. In the study reported here, the reflexes associated with muscles which act about the ankle joint of the decerebrate cat were investigated. Actions of autogenic pathways were measured by imposing length changes on the muscle and recording the resulting changes in force and EMG (electromyogram). Actions of heterogenic reflexes for pairs of muscles were measured by imposing appropriate combinations of length changes on the muscle of origin and on the muscle receiving the heterogenic reflex. In some cases, length changes were applied in such a way as to mimic normal mechanical coupling to evaluate the physiological importance of the reflexes, while in other cases the tests departed from normal coupling to address questions about mechanisms of reflex action. It was found that several pairs of muscles could be studied in a single experiment so that supraspinal influences on the pattern of spinal reflex connectivity can be conveniently evaluated.

Animals↗

Correction for the influence of background muscle activity on stretch reflex amplitudes.

Background muscle activity (BGR) exerts a strong influence on stretch reflex amplitudes. While it is considered important to correct for this influence, which method best able to eliminate the effects of BGR remains unknown. We have therefore compared one previously described and one novel correction method which respectively consisted of calculating (1) the difference between reflex amplitude and BGR, and (2) the ratio of reflex amplitude to BGR. These correction methods were evaluated in a group of 23 healthy individuals. BGR and stretch reflexes were recorded from the gastrocnemius muscle of standing subjects who received sudden toe-up perturbations of a supporting platform upon which they were standing. Calculation of differences markedly reduced the influence of BGR on stretch reflex amplitudes in most, although not all, subjects. Calculation of ratios failed to correct for BGR in most subjects and caused a net increase in the influence of BGR on stretch reflex amplitudes. Because both correction methods insufficiently corrected for BGR in normal subjects, we introduce the use of analysis of covariance (ANCOVA) to reliably remove the influence of BGR on stretch reflex amplitudes. The use of ANCOVA is exemplified by showing that stretch reflex amplitudes are enhanced in patients with Parkinson's disease even if the influence of high BGR is completely taken into account.

Adult↗

New insights into the organization of a gastroduodenal inhibitory reflex by the coeliac plexus.

The mechanisms involved at the prevertebral ganglionic level in a gastroduodenal inhibitory reflex were investigated in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and duodenum. Intraluminal gastric and duodenal pressures were measured using water-filled balloons. Gastric distension inhibited duodenal motility via a nerve reflex which was abolished by section of the nerves connecting the coeliac plexus to the viscera. Superfusion of the coeliac plexus with a low Ca(2+)-high Mg2+ solution abolished the gastroduodenal inhibitory reflex, indicating a synaptic link at the ganglion level. The reflex was unaffected by superfusion of the coeliac plexus with hexamethonium and tubocurarine, ruling out a nicotinic mechanism. The reflex persisted when the coeliac plexus was superfused with tetrodotoxin or when the nerves connecting the coeliac plexus to the viscera were superfused with a Na(+)-free solution; these results indicate that the reflex does not involve sodium-dependent action potentials. Moreover, superfusion of the nerves connecting the coeliac plexus to the viscera with a calcium blocker or with a Ca(2+)-free solution also failed to abolish the reflex, suggesting that calcium-dependent action potentials are not involved. Our study demonstrates that a gastrointestinal inhibitory reflex via the coeliac ganglion is not based on fast synaptic inputs or action potentials. These results provide new insights concerning the physiology of the sympathetic prevertebral ganglia.

Animals↗

Development of the monosynaptic reflex pathway in the human spinal cord.

Development of the monosynaptic reflex pathway of the spinal cord was investigated in 96 neurologically normal infants with ages ranging from 25 weeks in postconceptional age (PCA) to 24 months after full-term delivery (PDA) by examining H-reflexes from the triceps surae and hypothenar muscles in terms of their incidence, latency and maximal size in reference to the maximal M-wave. The triceps H-reflex was evoked in all cases, and the latency was longest (26 ms) in the youngest case of 25 weeks (PCA). It gradually shortened until full-term gestation, reaching the shortest value of 17 ms (mean). The H-reflex size initially increased until full-term gestation, reaching the maximum value of 70% and then reducing gradually to the plateau level of about 30% at 12 months (PDA). The hypothenar H-reflex could not be elicited until 32 weeks (PCA). The time course of changes in its latency and size was similar to those of the triceps H-reflex, except that it could not be elicited after 12 months (PDA). Thus, the monosynaptic reflex pathway is already functioning at the age of 25 weeks (PCA) in man. The significance of the systematic change in latency and excitability of the H-reflex with age is discussed.

Aging↗

Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine.

In neonatal kittens, micturition is induced by a spinal somatovesical reflex pathway that is activated by the mother cat licking the perigenital region of the kitten. The somatovesical reflex pathway disappears about the time of weaning and is replaced by a vesicovesical reflex pathway that produces micturition via a supraspinal reflex pathway that is activated by distension of the urinary bladder. Furthermore, stimulation of the perigenital region in adult cats actually inhibits the supraspinal vesicovesical micturition reflex. Spinalization prompts the return of the somatovesical reflex, immediately in weaned kittens but over a course of days to weeks in adult cats. The purpose of the present experiments was to determine if the somatovesical reflex could be demonstrated acutely, and reversibly, in adult cats with an intact spinal cord via pharmacological suppression of the serotonergic system. The serotonergic system was suppressed by the intravenous administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a serotonin agonist that inhibits the firing of serotonergic neurons via activation of inhibitory somatodendritic autoreceptors. 5-MeODMT in low doses (20-50 micrograms/kg) abolished inhibition of the bladder produced by either light tactile stimulation of the perigenital region or by electrical stimulation of the pudendal nerve, which carries the afferent fibers from the perigenital region, in 9 of 10 adult cats. Furthermore, in 8 of the 10 cats, the bladder inhibition was reversed to an excitation of variable amplitudes in each cat. Higher doses of 5-MeODMT (100-1000 micrograms/kg) abolished spontaneous bladder activity but did not inhibit perigenital-induced bladder contractions in those 8 animals in which the drug unmasked the excitatory somatovesical reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

The effects of intrathecal galanin message-associated peptide (GMAP) on the flexor reflex in rats.

We have examined the effects of intrathecal (i.t.) galanin message-associated peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor protein, which is produced in equimolar quantities with galanin and which is upregulated upon axotomy, on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of the flexor reflex. No depression of baseline flexor reflex was observed with any dose of GMAP. The facilitation of the flexor reflex induced by conditioning stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP. The reflex facilitatory effect of exogenously applied substance P (SP), one of the endogenous modulators of reflex hyperexicitability following C-fiber CS, was only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the reflex facilitatory effect of vasoactive intestinal peptide and did not potentiate the reflex depressive effect of i.t. morphine or clonidine. Finally, 1 micrograms i.t. GMAP did not influence spinal cord blood flow whereas 10 micrograms GMAP induced a transient decrease in spinal cord blood flow in some experiments. The ability of GMAP to block the increase in spinal cord excitability following repetitive C-fiber stimulation may be through a presynaptic action. Although some of the effects of GMAP were similar to galanin, distinct differences were found, particularly in interaction with other excitatory and inhibitory agents. It is possible that GMAP exerts its action in the spinal cord through its own specific receptor. GMAP may act similarly to GAL in some, but not all pharmacological functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics, Opioid↗

Electrophysiological study of superficial abdominal reflexes in normal men.

We studied the superficial abdominal reflexes of 83 normal men, using as stimuli a train of electrical pulses or a needle scratch. Electrical stimulation delivered to the midline of the abdominal wall evoked, almost symmetrically on both sides, two reflex discharges: an early response having an oligophasic wave form, and a late response of polyphasic wave form. The threshold of the early response significantly exceeded that of the late response. With repetitive stimulation, the late response generally revealed habituation. Electrical stimulation of the unilateral abdominal wall evoked two responses on the stimulated side, whereas it evoked only the late response on the contralateral side. A needle scratch on the unilateral abdominal wall evoked one reflex discharge with a long latency and a polyphasic wave form. This response occurred generally on the stimulated side and became habituated to repeated scratching. These observations suggest that the superficial abdominal reflexes elicited by electrical stimulation are composed of two reflex discharges with a different reflex arc. They appear to closely resemble the blink reflex. The response elicited by needle scratching is thought to correspond to the late response of the electrically elicited abdominal reflexes.

Adult↗