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R J Milne

Publications and source records attributed to R J Milne.

31 records · Page 2Linked to original sources

Reduction in perceived intensity of cutaneous stimuli during movement: a quantitative study.

The effect of movement of the index finger on the perceived intensity of trains of electrical stimuli to the digital nerves of the same finger was studied quantitatively using a novel intramodality stimulus-matching task. Subjects consistently were able to match reliably the perceived intensity of stimuli delivered on the 'reference' side with that of stimuli delivered simultaneously to the digital nerves of the index finger on the other ('matching') side. Both active and passive movement of the index finger (on the reference side) in the palmar plane reduced the matched stimulus voltage by about 10% of its control value for stimuli at twice the sensory threshold. This reduction in perceived intensity did not persist beyond the period of stimulation. An isometric contraction of first dorsal interosseous muscle produced a smaller, but statistically significant, reduction in perceived intensity. Non-noxious electrical stimulation of the digital nerves of the ipsilateral thumb or little finger also reduced the perceived intensity of stimuli to the index finger. Perceived intensity of stimuli during movement was also reduced, but to a lesser extent, when the index finger was stimulated at painful levels. Psychophysical studies using open magnitude scaling indicated that the relationship between stimulus intensity and perceived magnitude of electrical stimuli could be described by a power law with an exponent close to 1.0. Therefore, the percentage reduction in matching voltage accurately represents the percentage decline in perceived intensity. These results suggest that the perceived intensity of cutaneous stimuli to the index finger over a range of intensities can be reduced by afferent activity from the hand. The motor command appears to play a relatively minor role in modulating the perceived intensity.

Adolescent↗

Changes in perceived heaviness and motor commands produced by cutaneous reflexes in man.

1. This study examined the relationship between the perceived heaviness of a weight and reflexes acting on the motoneurones required for the contraction. The perceived heaviness of low (100 g) and high (500 g) reference weights lifted by the first dorsal interosseous muscle was estimated using a matching task. Weights were also lifted during stimulation of the digital nerves of the index finger at two times and four times sensory threshold (T). Averages of force and EMG were also made when isometric forces of 100 and 500 g were maintained. 2. Stimuli at 4T produced a significant increase in perceived heaviness in each subject for both reference weights. Averages of EMG made under isometric conditions showed a short-latency inhibition with a reflex reduction in force following single stimuli. This inhibition was also observed during weight lifting when trains of stimuli were given. 3. Stimuli at 2T produced less-marked changes in EMG, averaged force, and perceived heaviness for individual subjects. However, for the group of subjects, perceived heaviness declined significantly with 2T stimuli for the 500 g but not the 100 g weight. This decrease in perceived heaviness was associated with evidence of short-latency facilitation within the motoneurone pool. 4. Inhibition of the motoneurone pool was associated with an increase and facilitation with a decrease in perceived heaviness. These observations favour a role for a signal of centrally generated motor command in the sensation of heaviness and provide insight as to how this signal must change when reflex inputs change and when high-threshold motoneurones are recruited.

Action Potentials↗

Contralateral intramuscular acupuncture-like electrical stimulation differentially changes the short-latency responses to muscle stretch.

Measurements were made from the human first dorsal interosseous and extensor digitorum communis muscles of the surface electromyographic activity reflexly produced by brief stretch of the muscle. For the first dorsal interosseous muscle, reflex EMG activity was also produced by electrical stimulation of the ulnar nerve at the wrist. The procedures were carried out before, during, and after 25 min of nonspecific, low-frequency electrical stimulation to the contralateral arm delivered through intramuscular electrodes. Control stimulation was delivered subcutaneously. The EMG recorded during a maintained contraction was rectified, filtered, and averaged. Two reflex components (M1 and M2) of the EMG response to muscle stretch or ulnar nerve stimulation were investigated. During nonspecific intramuscular stimulation to the contralateral arm, M1 responses of the extensor digitorum communis were depressed, initially by 37%. The effect began to fade during stimulation but extended beyond it. Reflex responses were elicited alternately by brief stretch of the first dorsal interosseus muscle and by electrical stimulation of the ulnar nerve in the same experiment. Nonspecific intramuscular stimulation to the contralateral arm depressed the M1 response to stretch, but had no effect on the M1 response to electrical stimulation. It is concluded that nonspecific intramuscular electrical stimulation reduces the amplitude of the M1 component of the response to brief stretch of contralateral muscle, either through depression of fusimotor activity or inhibition of oligosynaptic pathways that contribute to the early reflex response.

Acupuncture Therapy↗

Intramuscular acupuncture-like electrical stimulation inhibits stretch reflexes in contralateral finger extensor muscles.

Electro-acupuncture is one of many physical measures used to relieve musculoskeletal pain and to improve the associated restricted range of motion. Experiments were designed to determine whether or not acupuncture-like stimulation inhibits stretch reflexes in an arm extensor muscle in human volunteers. Surface electromyographic recordings were made on the right extensor digitorum communis muscle and averaging techniques were used to study the reflex responses to brief deflection of the finger with a solenoid-driven probe. The ratio M1:M2 of two components of the reflex was reduced during continuous acupuncture-like stimulation of the contralateral first dorsal interosseus and extensor digitorum communis muscles near their motor points (acupuncture points LI 4 and LI 11). Concomitant changes in skin temperature were observed on the forehead and in the arm in which acupuncture-like stimulation was used. In control experiments, when the acupuncture needles were inserted subcutaneously and stimulated with the same current parameters at distinctly uncomfortable intensities, no change in the reflexes occurred. These findings show that acupuncture-like stimulation exerts physiologic effects on the central nervous system, mediated presumably by muscle afferent fibers. The effects may be relevant to relief of muscle spasm and musculoskeletal pain, and restoration of mobility.

Arm↗

Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (Stilling's nucleus) to proprioceptive input from the tail.

Extracellular an intracellular recordings were obtained from 24 spinothalamic neurons located in the intermediomedial gray (Stilling's nucleus) in the S2 and S3 spinal segments of anesthetized adult monkeys (Macaca fascicularis). Most units were spontaneously active. They lacked cutaneous receptive fields but could be excited by subcutaneous receptors. Bending the tail to one side of the animal's body axis excited cells located on the contralateral side of the cord an inhibited ipsilateral cells. The firing rate of each cell was a reproducible function of the angle of the portion of the tail distal to the innervated segment. Cells responded with a burst of spikes to electrical stimulation of low threshold ipsilateral primary afferent fibers in the homosegmental dorsal root. The latency of the underlying synaptic potential was 0.5-0.7 ms from the time of arrival of the afferent volley at the cord, indicating monosynaptic input. Low intensity stimulation of the contralateral homosegmental dorsal root inhibited back-ground activity. The latency of the underlying inhibitory synaptic potential was 0.8-1.1 ms, suggesting crossed disynaptic inhibition. We conclude that sacral spinothalamic tract neurons located in the intermediomedial gray participate in signalling the spatial orientation of the animal's tail.

Animals↗

Parasympathetic preganglionic neurons in the sacral spinal cord.

Two types of preganglionic neurons have been identified in the sacral parasympathetic nucleus (SPN) of the cat. These neurons could be differentiated by various characteristics including axonal conduction velocities, morphology, location in the nucleus, organ of innervation and central reflex mechanisms controlling their activity. Neurons having myelinated axons (B-PGNs) with conduction velocities between 3.3 and 13 m/s were located in the lateral band of the SPN and innervated the urinary bladder. Neurons with unmyelinated axons (C-PGNs) with conduction velocities of 0.5-1.4 m/s were located in the dorsal band of the nucleus and innervated the large intestine. B-PGNs were excited by distention of the bladder and inhibited by distension or mechanical stimulation of the intestine, whereas C-PGNs exhibited the opposite responses to these stimuli. C-PGNs often exhibited a low level of spontaneous discharge in absence of stimulation but exhibited marked firing (3.5-10 spikes/s) during a defecation reflex elicited by mechanical stimulation of the rectum-anal canal. The excitatory responses were elicited by C-fiber afferents via a spinal reflex pathway. B-PGNs were inactive when intravesical pressure was below the threshold for inducing micturition (5 cm H2O) but raising the pressure above the threshold induced firing consisting of repetitive bursts of action potentials occurring at relatively high frequencies (15-60 spikes/s). These bursts coincided with rhythmic bladder contractions. The frequency of bladder contractions and associated bursts of PGN-firing and the mean PGN-firing rate (2-8 spikes/s) increased as intravesical pressure was increased in steps between 5 and 30 cm H2O. However, as indicated by interspike interval histograms, the frequency of firing within a burst of action potentials was unchanged. It is concluded that the micturition reflex pathway is organized as a simple on-off switching circuit and that B-PGNs receive a maximal synaptic input when intravesical pressure exceeds the micturition threshold. This circuit was triggered by vesical A delta afferents via a spinobulbospinal pathway. Transection of the spinal cord interrupted the reflex pathway and blocked micturition. However, in chronic spinal animals a spinal reflex mechanisms emerged which contributed to the recovery of bladder function. This mechanism, which was weak or non-existent in animals with an intact neuraxis, exhibited a number of important differences from the normal micturition reflex, most notably being activated by a C-fiber afferent rather than a A delta afferent limb. The mechanism underlying the emergence of C-fiber evoked bladder reflexes in spinal animals is uncertain.

Action Potentials↗

Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine.

Electrophysiological and horseradish peroxidase (HRP) techniques have provided new insights into the organization of the sacral parasympathetic reflex pathways to the large intestine and urinary bladder. The innervation of the two organs arises from separate groups of sacral preganglionic cells: (1) a dorsal band of cells in laminae V and VI providing an input to the intestine; and (2) a lateral band of cells in lamina VII providing an input to the bladder. These two groups of cells were separated by an interband region containing tract cells and interneurons. Neurons in the interband region received a visceral afferent input and exhibited firing correlated with the activity of intestine and urinary bladder. It seems reasonable therefore to consider the interband region as a third component of the sacral parasympathetic nucleus. Anterograde transport of HRP revealed that visceral afferents from the intestine and bladder projected into the parasympathetic nucleus. Most of the projections were collaterals from afferent axons in Lissauer's tract that passed in lamina I laterally and medially around the dorsal horn. These afferent collaterals were located in close proximity to preganglionic perikarya and dendrites in laminae I, V and VI. The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays (45-70 msec). The reflex pathways mediating defecation and micturition in cats with an intact neuraxis were markedly different. Defecation was dependent upon a spinal reflex with unmyelinated (C-fiber) peripheral afferent and efferent limbs. On the other hand, micturition was mediated by a spinobulbospinal pathway with myelinated peripheral afferent (A-fiber) and efferent axons (B-fiber). Transection of the spinal cord at T12-L2 blocked the micturition reflex but only transiently depressed the defecation reflex. In chronic spinal cats the micturition reflex recovered 1-2 weeks after spinalization; however, in these animals bladder-to-bladder micturition reflexes were elicited by C-fiber rather than A-fiber afferents. The C-fiber afferent-evoked reflex was weak or undetectable in animals with an intact neuraxis. Transection of the spinal cord also changed the micturition reflex in neonatal kittens (age 5-28 days). In neonates with an intact neuraxis bladder-to-bladder reflexes occurred via a long latency spinobulbospinal pathway (325-430 msec). The long latency is attributable to the slow conduction velocity in immature unmyelinated peripheral and central axons. In chronic spinal kittens (3-7 days after spinalization) the long latency reflex was abolished and a shorter latency (90-150 msec) bladder reflex was unmasked. The emergence of this spinal pathway may reflect axonal sprouting and the formation of new reflex connections within the sacral parasympathetic nucleus.

Afferent Pathways↗

Convergence of cutaneous and pelvic visceral nociceptive inputs onto primate spinothalamic neurons.

The responses of 66 primate spinothalamic neurons to natural stimulation the the urinary bladder and testicle were studied with extracellular recording techniques in order to elucidate the neural basis for referral of visceral pain. Thirty-eight out of 53 cells located at the thoraco-lumbar junction or in sacral segments responded to noxious cutaneous stimuli, and 84% of these also exhibited phasic and/or tonic excitatory responses to distension of the urinary bladder. Seventeen out of 20 of these units, all located at the thoraco-lumbar junction, were excited by compression of the ipsilateral testicle. The response was graded with the compressive force. Excitatory responses to noxious heat and an irritant chemical (KC1) applied to the exposed testicular surface were also observed. Twelve sacral units having inputs from deep receptor of the tail exhibited mixed excitatory and inhibitory responses to bladder distension. A further 2 cells located at the thoracolumbar junction responded only to cutaneous tactile stimuli, and 13 cells located at the lumbosacral enlargement were tonically inhibited by bladder distension. It is concluded that spinothalamic neurons that convey nociceptive input from the skin may also respond to noxious visceral stimuli. Such viscero-somatic convergence provides a neural substrate for the phenomenon of cutaneous referral of visceral pain.

Animals↗

Effects of 2,4-dinitrophenol amylobarbitone and certain other drugs on the rate of oxygen consumption and force of contraction of isolated curarized diaphragm muscle of the rat.

1 A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically-induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.2 The resting oxygen consumption of the muscle was increased substantially by 2,4-dinitrophenol in concentrations (0.02 mM and higher) that eventually produced contracture. Two other uncoupling agents, 4,6-dinitro-o-cresol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, behaved similarly.3 The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4-dinitrophenol (0.05 mM), although the strength of the ;maximal' contractions was lessened.4 Amylobarbitone increased the strength of contraction at a concentration (0.2 mM) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mM) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mM. Phenobarbitone had a weaker action.5 S-n-decyl-thiouronium increased oxygen consumption when given at a concentration (1 mM) that diminished strength of contraction and eventually produced contracture of the muscle.6 Both S-methyl-thiouronium (1 mM) and 4-aminopyridine (0.1 mM and 0.5 mM) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mM) or by phenformin (0.1 mM).7 It is concluded that the response to 2,4-dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S-n-decyl-thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4-aminopyridine and S-methyl-thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non-metabolic action.

Amobarbital↗

Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction.

1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited.

Acetylcholine↗