Effect of (-)-N-[(S)-hexahydro-l-methyl-2, 6-dioxo-4-pyrimidinylcarbonyl]-L-histidyl-L-prolinamide (TA-0910), a new TRH analog, on plasma levels of TSH and thyroid hormones in rats

The stimulatory effect of TA-0910 on the secretions of thyroid-stimulating hormone (TSH) and thyroid hormones was investigated in male and female rats. Single intravenous administration of TA-0910 at 8.3 nmol/body acutely elevated the plasma TSH level, with delayed and moderate increases of T3 and T4 in plasma. Similar increments of plasma TSH and thyroid hormones were observed when TRH was injected at the dose of 0.83 nmol/body. Oral administration of TA-0910 at 2.75 mumol/body was equally potent or slightly more potent to secrete TSH than TRH at 0.275 mumol/body. The elevated TSH by TA-0910 decreased to the control level within 2 hr after intravenous injection or within 6 hr after oral administration; on the other hand, the higher levels of the thyroid hormones were retained for up to 4 and 6 hr after intravenous and oral administration, respectively. These findings indicate that TA-0910 and TRH stimulate the secretion of TSH and thyroid hormones by a similar manner and that the TSH-secreting activity of TA-0910 is lower by an order of magnitude compared with that of TRH.     

TRH receptor agonists ameliorate 3-acetylpyridine-induced ataxia through NMDA receptors in rats

The effects of thyrotropin-releasing hormone (TRH) receptor agonists were examined on 3-acetylpyridine-induced cerebellar ataxia in rats. 3-acetylpyridine markedly decreased the maximal height of vertical jump, accompanied by motor incoordination. Both TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate; 0.3-3 mg/kg), a novel TRH analog, and TRH (10 and 30 mg/kg) significantly increased the suppressed maximal height of vertical jump after single intraperitoneal administration. The effects of these drugs reached a maximum at 1 h and disappeared 24 h after administration. Both the TA-0910 (1 mg/kg)- and TRH (10 mg/kg)-induced increases in the maximal height of vertical jump were completely counteracted by pretreatment with i.p. injected MK-801 (10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; 0.1 mg/kg), an NMDA receptor antagonist. Neither bicuculline, muscimol, baclofen, cyproheptadine nor prazosin affected the effect of the TRH receptor agonists. In conclusion, TA-0910 is more potent than TRH in ameliorating cerebellar functional disorders. The anti-ataxic effects of these TRH receptor agonists may be mediated by NMDA receptors in 3-acetylpyridine-treated rats.     

Bacterial toxins block endothelial wound repair. Evidence that Rho GTPases control cytoskeletal rearrangements in migrating endothelial cells

Pharmacological experiments were conducted to determine the neuronal mechanisms involved in the suppressive effects of the thyrotropin-releasing hormone analog TA-0910 on alcohol intake in alcohol-preferring (P) rats. We previously reported that single intraperitoneal injections of TA-0910 dose-dependently reduced alcohol intake in P rats without altering fluid or total calorie intake; however, after several consecutive, once-daily injections, P rats developed tolerance to the suppressive effects of TA-0910 on alcohol intake and cross-tolerance to like effects of the dopamine D2 agonist bromocriptine, but not to like effects of the serotonin uptake inhibitor fluoxetine. In the present study, rats were injected with vehicle or different doses of the D2 antagonist s(-)-eticlopride (0.01 to 0.05 mg/kg) or the D1 antagonist R(+)-SCH23390 (0.1 to 0.5 mg/kg) and 20 min later with TA-0910 (0.75 mg/kg). Alcohol and water intakes were measured at 2, 4, 6, and 24 hr, and food was measured every 24 hr. Both s(-)-eticlopride and R(+)-SCH23390 produced modest reductions in alcohol intake alone; however, only s(-)-eticlopride antagonized the suppressive effect of TA-0910 on alcohol intake. In related experiments, it was confirmed that the dopamine D3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin reduced alcohol intake in P rats, and it was found that tolerance to this effect did not develop during or after seven consecutive once-daily injections. Furthermore, this effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin was not diminished in rats made tolerant to the effect of TA-0910 on alcohol intake. These data, those of previous studies, and recent preliminary findings support involvement of dopamine D2, but not D1 or D3 receptors in mediating the suppressive effect of TA-0910 on alcohol intake of P rats.     

Comparison of morphine-induced effects on thermal nociception, mechanoreception, and hind limb flexion in chronic spinal rats.

The effect of systemic morphine on 3 behaviors in the same group of chronic spinal rats was examined: the tail-flick (TF) reflex to a noxious thermal stimulus, limb withdrawal (LW) to mechanoreceptor (von Frey hair) stimulation, and hind limb flexion (flexor reflex [FR]) elicited by innocuous electrical stimulation of the toes. Compared with intact rats, the potency of morphine on both the TF and the hind paw (but not the forepaw) LW response was significantly reduced. Morphine's effect on the FR depended on the dose. The lowest dose (1.0 mg/kg) produced no change, 4.0 mg/kg decreased response magnitude by approximately 50% (indicating an antispastic effect), and 8.0 mg/kg increased flexor magnitude by 100%. The concurrent TF and FR assays revealed a dissociation of morphine's effects in that the highest dose (8.0 mg/kg) significantly inhibited the nociceptive TF response but facilitated the FR in the same chronic spinal rats. This outcome may be relevant to the phenomenon of "opioid-related myoclonus" recently described in cancer patients, which "was highly associated with nerve dysfunction due to spinal cord lesions" (S. Mercadante, 1998, p. 6). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spasticity in rats with sacral spinal cord injury

We have investigated sacral spinal cord lesions in rats with the goal of developing a rat model of muscular spasticity that is minimally disruptive, not interfering with bladder, bowel, or hindlimb locomotor function. Spinal transections were made at the S2 sacral level and, thus, only affected the tail musculature. After spinal transection, the muscles of the tail were inactive for 2 weeks. Following this initial period, hypertonia, hyperreflexia, and clonus developed in the tail, and grew more pronounced with time. These changes were assessed in the awake rat, since the tail is readily accessible and easy to manipulate. Muscle stretch or cutaneous stimulation of the tail produced muscle spasms and marked increases in muscle tone, as measured with force and electromyographic recordings. When the tail was unconstrained, spontaneous or reflex induced flexor and extensor spasms coiled the tail. Movement during the spasms often triggered clonus in the end of the tail. The tail hair and skin were extremely hyperreflexive to light touch, withdrawing quickly at contact, and at times clonus could be entrained by repeated contact of the tail on a surface. Segmental tail muscle reflexes, e.g., Hoffman reflexes (H-reflexes), were measured before and after spinalization, and increased significantly 2 weeks after transection. These results suggest that sacral spinal rats develop symptoms of spasticity in tail muscles with similar characteristics to those seen in limb muscles of humans with spinal cord injury, and thus provide a convenient preparation for studying this condition.     

Stretch reflex and servo action in a variety of human muscles

1. In the long flexor of the thumb the latency of the stretch reflex and of other manifestations of servo action is some 45 msec, roughly double the latency of a finger jerk. 2. Tendon jerks are feeble or absent in the long flexor of the thumb even in subjects with brisk long-latency stretch reflexes in this muscle. This, and other facts, suggests that the nervous mechanism of the tendon jerk is different from that of the stretch reflex. 3. A muscle that has feeble tendon jerks may show a late component in the response to a tendon tap, with a latency similar to that of the long-latency stretch reflex. 4. On the hypothesis that the excess latency of the stretch reflex over that of a tendon jerk is because the stretch reflex employs a cortical rather than a spinal arc, the excess would be expected to be larger in magnitude for the long flexor of the big toe and smaller for the jaw closing muscles. This is confirmed, 5. An alternative hypothesis that the long latency of stretch reflexes in thumb and toe is because they are excited by slow-conducting afferents is made improbable by the finding that stretch reflexes with an equal or greater excess latency are also found in proximal arm muscles. 6. The long-latency stretch reflex in proximal muscles was seen most distinctly in a healthy subject who happened to have feeble or absent tendon jerks. In ordinary subjects there is often a large, short-latency, presumably spinal component of the stretch reflex in proximal muscles; and short-latency responses to halt and release are also seen, The significance of this spinal latency servo action in proximal muscles remains to be explored. 7. The Discussion argues that the available data on conduction time to and from the cerebral cortex are compatible with the hypothesis that the long-latency component of the stretch reflex uses a transcortical reflex arc, and that none of the experiments described in the present paper are inimical to this view.     

Effects of ketamine on somatosympathetic reflex discharges in cats

Effects of ketamine on somatosympathetic reflex discharges induced from sympathetic trunk with electrical stimulation of superficial peroneal nerve were investigated in 51 cats under anesthesia with urethane and alpha chloralose. These reflex discharges through spinal cord and medulla oblongata consist of two components, A and C reflexes, which are derived from somatic myelinated and unmyelinated afferent fiber respectively. Amplitudes of both A and C reflex potentials were depressed significantly after intravenous injection of ketamine 10 mg.kg-1. The maximum depression was observed 5 min after administration. In decerebrated cats with surgical transection at the midbrain, both A and C reflexes were also depressed after administration of the same dosages, and the maximum level of the depression was more profound than that in brain intact cats. After intrathecal injection of ketamine 1 mg.kg-1 to the lumbar spinal region, a slight depression of C reflex was found, but, dosages of 10 mg.kg-1 significantly depressed both A and C reflexes to the similar levels as those in iv injection to brain intact cats. The maximum depression was observed 30 min after administration. The depressive effects on both reflexes of intravenous ketamine 10 mg.kg-1 were not antagonized by naloxone 0.06 mg.kg-1 in brain intact cats. These results suggest that the suppressive effects of ketamine on somatosympathetic reflexes are caused by direct inhibition of medulla oblongata and spinal cord, whereas supra-midbrain regions may be activated by ketamine, and the effect of ketamine is predominant on medulla oblongata in this situation rather than on the spinal cord.     

On spinal noradrenaline receptor supersensitivity: correlation between nerve terminal densities and flexor reflexes various times after intracisternal 6-hydroxydopamine

The noradrenaline (NA)-dependent hindlimb flexor reflex that can be elicited by pinching the foot of acutely spinalized rats given nialamide-DOPA or clonidine was evaluated different time intervals (14 days-6 months) after intracisternal injections of 6-OH-dopamine (6-OH-DA) and correlated to the degree of bulbospinal catecholamine (CA) denervation as seen by Falck-Hillarp fluorescence histochemistry. Six and 14 days after 6-OH-DA, when almost all NA nerve terminals of the spinal cord had degenerated, the NA receptors where supersensitive to stimulation with clonidine as evidenced by an increased flexor reflex. This supersensitivity gradually disappeared as new nerve terminals were formed in the grey matter of the spinal cord during the following 3-6 months. The supersensitivity phenomenon 14 days after 6-OH-DA could also be demonstrated by L-DOPA given to animals pretreated with 100 mg/kg nialamide. Using this relatively low dose of nialamide, almost no reflex response was seen in the control group. Using a higher degree of monoaminoxidase inhibition (nialamide 200 mg/kg) also non-supersensitive, NA receptors became maximally stimulated. Therefore, 6-OH-DA treated rats now showed a weaker reflex than controls, the reflex response being directly correlated to the number of nerve terminals present that could form NA from the precursor. Using 5,6-dihydroxytryptamine, which selectively destroys 5-hydroxytryptamine (5-HT) nerves, it was shown that the flexor reflex changes were specifically related to the NA nerves and unchanged by the simultaneous presence or absence of 5-HT nerve terminals. This was further supported by the finding of a correlation between amount of nerve terminals and flexor reflex responses in individual animals, especially at longer survival times both in the clonidine and the nialamide-DOPA experiments.     

Fixation of spinal reflex alterations in spinal rats by sensory nerve stimulation.

Two preparations in which sensory nerve stimulation was used to obtain peripherally induced spinal fixation in spinal rats are described. In the first preparation, proportionally greater amounts of persisting poststimulation flexor muscle contraction, as measured by a force displacement transducer, were produced as stimulation time was increased from 10 min to 40 min. In the second preparation, sensory nerve stimulation was delivered, and evoked whole-nerve responses were recorded from a flexor motor nerve. Results indicated that 30 min or more of sensory nerve stimulation produced increases in response amplitude and area that persisted for at least 30 min after stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of intrathecal alpha1- and alpha2-noradrenergic agonists and norepinephrine on locomotion in chronic spinal cats

Noradrenergic drugs, acting on alpha adrenoceptors, have been found to play an important role in the initiation and modulation of locomotor pattern in adult cats after spinal cord transection. There are at least two subtypes of alpha adrenoceptors, alpha1 and alpha2 adrenoceptors. The aim of this study was to investigate the effects of selective alpha1 and alpha2 agonists in the initiation and modulation of locomotion in adult chronic cats in the early and late stages after complete transection at T13. Five cats, chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used in this study. Noradrenergic drugs including alpha2 agonists (clonidine, tizanidine, and oxymetazoline) and an antagonist, yohimbine, one alpha1 agonist (methoxamine), and a blocker, prazosin, as well as norepinephrine were injected intrathecally. EMG activity synchronized to video images of the hindlimbs were recorded before and after each drug injection. The results show differential effects of alpha1 and alpha2 agonists in the initiation of locomotion in early spinal cats (i.e., in the first week or so when there is no spontaneous locomotion) and in the modulation of locomotion and cutaneous reflexes in the late-spinal cats (i.e., when cats have recovered spontaneous locomotion). In early spinal cats, all three alpha2 agonists were found to initiate locomotion, although their action had a different time course. The alpha1 agonist methoxamine induced bouts of nice locomotor activity in three spinal cats some hours after injection but only induced sustained locomotion in one cat in which the effects were blocked by the alpha1 antagonist prazosin. In late spinal cats, although alpha2 agonists markedly increased the cycle duration and flexor muscle burst duration and decreased the weight support or extensor activity (effects blocked by an alpha2 antagonist, yohimbine), alpha1 agonist increased the weight support and primarily the extensor activity of the hindlimbs without markedly changing the timing of the step cycle. Although alpha2 agonists, especially clonidine, markedly reduced the cutaneous excitability and augmented the foot drag, the alpha1 agonist was found to increase the cutaneous reflex excitability. This is in line with previously reported differential effects of activation of the two receptors on motoneuron excitability and reflex transmission. Noradrenaline, the neurotransmitter itself, increased the cycle duration and at the same time retained the cutaneous excitability, thus exerting both alpha1 and alpha2 effects. This work therefore suggests that different subclasses of noradrenergic drugs could be used to more specifically target aspects of locomotor deficits in patients after spinal injury or diseases.     

Tolerance to the antinociceptive effect of morphine in spinally transected rats.

Examined the effect of a spinal transection (ST) on morphine (MOR)-induced tolerance in rats with the tail withdrawal reflex (tail flick; TF), elicited by noxious thermal stimulation. Intact Ss became tolerant to sc MOR injections if they were tested on the TF after each injection. MOR administration alone did not produce tolerance; TF tests alone did, although not always to a significant extent. However, when MOR only, TF tests only, or both were administered prior to ST (acute spinal Ss), all groups were tolerant when tested 1 day after spinalization. When the same treatments were administered to Ss 3 wks after ST (chronic spinal Ss), neither MOR nor TF tests alone produced tolerance. Chronic spinal Ss became tolerant only if they were tested after each injection. Results suggest that tolerance develops at the spinal cord as a result of either chronic opiate exposure or performance of the nociceptive response, but in intact Ss, tolerance is inhibited or suppressed by a supraspinal action of MOR. Results also suggest that such tolerance is mediated by descending input or that ST produced intrinsic changes in the spinal cord that preclude the development of tolerance induced only by opiate or behavioral stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function

The purpose of this study is to investigate the effects of aging on the human stretch reflexes. The EMG and torque responses of the stretch reflex of the wrist flexors were evoked by ramp-and-hold mechanical perturbations. The stretch reflexes were recorded at seven test conditions with different stretch velocity and muscle preload. The test results from young and older healthy adult subjects were compared. In average, the absolute amplitude of the short-latency (20-40 ms) EMG (recorded from flexor carpi radialis) reflex response was significantly lower in the older group. If the data were normalized and expressed in percentage of the maximal voluntary EMG activity, however, this group difference was not significant. There was no change in the reflex gain of the short-latency reflex with aging. For the long-latency (50-90 ms) EMG reflex response, both the normalized amplitude and the reflex gain were significantly enhanced with aging, probably through supraspinal mechanisms. There was no significant difference in the threshold velocity for the evoked EMG reflexive activities between age groups. There were also no changes in the reflexive wrist flexion torque with aging. These results suggested that the number of motor units recruited during the stretch reflex activity declined with aging although the percentage of motor units recruited was not affected by aging. It is concluded that the central regulating mechanisms of the spinal motoneuron excitability are not compromised by aging. The automatic gain compensation phenomenon is also preserved with aging.     

Triplex-directed self-assembly of an artificial sliding clamp on duplex DNA

Little is known about extrinsic-intrinsic reflexes, especially the prototype combinative extensor hallucis response, which become apparent if proprioceptive and exteroceptive afferents of the concerning muscles are stimulated simultaneously as well as successively. With reference to this phenomenon, data from 604 patients were evaluated under neurological aspects. With the exception of the combinative reflex of the peroneal muscles, the occurrence of other combinative reflexes (of tibial posterior, anterior and extensor hallucis muscles) was of clinical relevance. All these characteristics, in the same way as Tramer's reflex and unilateral tibialis posterior reflex, correlated very well statistically with typical symptoms of an upper motor neurone syndrome. In this context the extensor hallucis combinative response is the most important one. This particular sign occurred in a systematically examined population of patients twice as often as Babinski's sign and was the single reflex anomaly in 7 per cent of 200 systematically examined cases. A double-sided manifestation, which could be seen exclusively as physiological, appeared in less than 2 per cent of 604 cases. In respect of the occurrence of combinative responses, patients belonging to different diagnostic groups, infants as well as adults, did not have statistically the same basic probability with regard to the examined neurological signs. Hence, an examination of healthy persons would not yield essential evidence. In our opinion such combinative reflexes and the other symptoms mentioned may be useful in detecting latent upper motor neuron lesion or may be helpful in doubtful cases. Whether or not the phenomenon of a combinative reflex really represents part of the latent pathognomonic flexor withdrawal reflex, cannot be decided with our clinical methods.     

Reconstruction of flexor/extensor alternation during fictive rostral scratching by two-site stimulation in the spinal turtle with a transverse spinal hemisection

Analyses of fictive scratching motor patterns in the spinal turtle with transverse hemisection provided support for the concept of bilateral shared spinal cord circuitry among neurons responsible for generating left- and right-side rostral, pocket, and caudal fictive scratching. Rhythmic bursts of hip flexor activity, the hip extensor deletion variation of fictive rostral scratching, were elicited by ipsilateral stimulation in the rostral scratch receptive field of a spinal turtle [transection at the segmental border between the second (D2) and third (D3) postcervical spinal segments] with a contralateral transverse hemisection one segment anterior to the hindlimb enlargement (at the D6-D7 segmental border). In addition, other sites were stimulated in this preparation: (1) contralateral sites in a rostral, pocket, or caudal scratch receptive field or (2) ipsilateral sites in a caudal scratch receptive field. A reconstructed fictive rostral scratch motor pattern of rhythmic alternation between hip flexor and hip extensor activation was produced by simultaneous stimulation of one site in the ipsilateral rostral scratch receptive field and another site in one of the other scratch receptive fields. This reconstructed rostral scratch motor pattern resembled the normal rostral scratch motor pattern produced by one-site rostral scratch stimulation of a spinal turtle (D2-D3 transection) with no additional transections. The observation of a reconstructed rostral scratch motor pattern produced by two-site stimulation in the spinal turtle with transverse hemisection supports the concept that hip extensor circuitry activated by stimulation of other scratch receptive fields is shared with circuitry activated by ipsilateral rostral scratch receptive field stimulation.     

Behavioral analysis of diffuse noxious inhibitory controls (DNIC): antinociception and escape reactions

'Diffuse noxious inhibitory controls' or DNIC is the inhibition of multireceptive neurons in the dorsal horn of the spinal cord that results when a noxious stimulus is applied to a region of the body remote from the neuron's excitatory receptive field. Although this phenomenon is well-documented, the behavioral consequences of DNIC are not clear. The present study was undertaken to determine how nocifensor withdrawal reflexes evoked by a noxious stimulus are altered by application of a second noxious stimulus to a distant part of the body. The tail flick or hindpaw withdrawal reflex of lightly anesthetized (0.6-1.0% halothane) rats was measured before, during and after another appendage was placed in water ranging in temperature from 45 to 54 degrees C. When the forepaw or hindpaw was placed in water exceeding 49 degrees C the tail flick reflex to acute noxious radiant heat was inhibited. In contrast, noxious conditioning stimuli, regardless of temperature or location, had no effect on the latency for hindpaw withdrawal evoked by an acute noxious stimulus, but did produce a change in reflex topography from flexion to extension. These results, along with previous research on DNIC, suggest that intense noxious stimuli: (1) inhibit the tail flick reflex via inhibition of multireceptive neurons in the dorsal horn; (2) disinhibit hindpaw extensor motoneurons by inhibiting the activity of multireceptive neurons involved in hindlimb flexion; and (3) reduce pain sensation by inhibiting multireceptive neurons projecting to the brain (see Model in Discussion).     

Effects of spinal cord ischemia on evoked potential recovery and postischemic regional spinal cord blood flow

The effects of spinal cord ischemia on spinal cord blood flow (SCBF) and somatosensory (SSEP) and motor (MEP) evoked potentials were investigated in a rabbit model of reversible spinal cord ischemia. Spinal cord ischemia was produced by balloon occlusion of the infrarenal aorta for 30, 60, and 90 min. SCBF, SSEPs, and MEPs were measured before, during, and 1 h after aortic occlusion. Aortic occlusion produced absolute ischemia of the caudal cord followed by hyperemia upon reperfusion. SSEP's and MEP's were obliterated during ischemia but demonstrated gradual albeit incomplete recovery following reperfusion with amplitude recovery inversely proportional to the duration of ischemia. Later peaks were more severely affected by a given period of ischemia than were early waves. In general, SSEP's were more resistant to ischemia than were MEP's although the differences were not significant.     

Effect of xylitol and trehalose on dry resistance of yeasts

Nitric Oxide (NO) has been implicated as a mediator of neuronal injury in vascular stroke. On the other hand, NO is suggested to play a neuroprotective role by increasing blood flow during cerebral ischemia. In order to evaluate the role of NO in the spinal cord ischemia, effects of nitric oxide synthase (NOS) inhibition on the recovery of reflex potentials after a transient spinal cord ischemia were examined in urethane-chloralose anesthetized spinal cats. Spinal cord ischemia was produced by occlusion of the thoracic aorta and the both internal mammary arteries for 10 min. Regional blood flow (RBF) in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials elicited by electrical stimulation of the tibial nerve, were recorded from the L7 or S1 ventral root. The recovery process of spinal reflex potentials was reproducible when the oclusion was repeated twice at an interval of 120 min. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 10 mg/kg), a NOS inhibitor significantly accelerated the recovery of PSR potentials after spinal cord ischemia. The accelerating effect of L-NMMA on the recovery of PSR potentials was abolished by co-administration of L-arginine (1 mg/kg/min) but not by that of D-arginine (1 mg/kg/min). L-NMMA failed to improve RBF in the spinal cord during ischemia and reperfusion. Nitroprusside (10 microg/kg/min), a NO donor, retarded the recovery of PSR potentials after spinal cord ischemia. These results suggest that NO production has a significant influence on the functional recovery after transient spinal cord ischemia.     

Wipe and flexion reflexes of the frog. I. Kinematics and EMG patterns

1. We evaluated the hypothesis that the neural control of complex motor behaviors is simplified by building movement sequences from a series of simple neural "building blocks." In particular, we compared two reflex behaviors of the frog, flexion withdrawal and the hindlimb-hindlimb wipe reflex, to determine whether a single neural circuit that coordinates flexion withdrawal is incorporated as the first element in a sequence of neural circuits comprising the wipe. The neural organization of these two reflexes was compared using a quantitative analysis of movement kinematics and muscle activity patterns [electromyograms (EMGs)]. 2. The three-dimensional coordinates of the position of the foot over time and the angular excursion of hip, knee, and ankle joints were recorded using a WATSMART infrared emitter-detector system. These data were quantified using principal-components analysis to provide a measure of the shape (eigenvalues) and orientation (eigen-vector coefficients) of the movement trajectories. The latencies and magnitudes of EMGs of seven muscles acting at the hip, knee, and ankle were analyzed over the interval from EMG onset to movement onset, and EMG magnitudes during the initial flexion of the limb. These variables were compared during flexion withdrawal and the initial flexion movement of the limb during the hindlimb-hindlimb wipe reflex (before the onset of the frequently rhythmic portion when the stimulus is removed) when the two reflexes were elicited from comparable stimulus locations. 3. In both the flexion reflex and the initial movement segment of the wipe reflex, the foot moves along a relatively straight line. However, the foot is directed to a more rostral and lateral position during flexion than during wipe. All three joints flex during flexion withdrawal, whereas during the wipe, the knee and ankle joints flex but the angular excursion of the hip joint may vary. The different orientations of the movement trajectories are associated with EMG patterns that differ in both timing and magnitude between the two reflexes. 4. The differences in the kinematics and EMG patterns of the two reflexes during unrestrained movements make it unlikely that the neural circuit that coordinates flexion withdrawal is incorporated as the first element in the sequence of neural circuits underlying the wipe reflex. 5. Unlike the wipe reflex, during flexion withdrawal there is no apparent constraint on the accuracy of placement at the end of the movement, yet the animals nevertheless achieved consistent final positions of both the foot and of each joint. The implications of these findings with respect to the controlled variables are discussed.     

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.