Polysynaptic reflex

Normal function Transduction Conduction Processing, mono- and polysynaptic-re-flexes Processing, perception, emotional components of pain, polysynaptic reflexes... 

Figure 7.3 Components of a reflex arc. As illustrated by the components of the reflex arc, reflexes may be processed entirely at the level of the spinal cord with no need for input from the brain. A monosynaptic reflex has a single synapse between afferent and efferent neurons a polysynaptic reflex has two or more synapses between these neurons. In this case, intemeurons lie between the sensory and motor neurons. The more intemeurons involved, the more complex the response is.

A reflex is initiated by stimulation of a sensory receptor located at the peripheral ending of an afferent or first-order sensory neuron. This afferent neuron transmits impulses to the spinal cord. Within the gray matter of the spinal cord, the afferent neuron synapses with other neurons. As such, the spinal cord serves as an integrating center for the sensory input. The afferent neuron must ultimately synapse with an efferent or motor neuron. When the afferent neuron synapses directly with the motor neuron, it forms a monosynaptic reflex. An example of this type of reflex is the stretch reflex. When the afferent neuron synapses with an intemeuron that then synapses with the motor neuron, it forms a polysynaptic reflex, e.g., the withdrawal reflex. Most reflexes are polysynaptic. The motor neuron then exits the spinal cord to innervate an effector tissue, which carries out the reflex response. 

An interneuron together with a sensory afferent and motor efferent form a polysynaptic reflex (Figure 2.2) this comprises the initial stage of information input (sensory afferent), the processing/computing an appropriate response (interneurons) and the execution of a behavioural response (motor efferent). The simplest reflexes in the nervous system are monosynaptic reflexes, such as the familiar tendon (knee) jerk, these do not involve an interneuron. The sensory afferent activated by the mechano-receptor (the tap of the patellar hammer) forms a synapse with the motor efferent in the spinal cord, which then causes the skeletal muscle to contract and the crossed leg to jerk forward. With a synaptic delay of 1 millisecond (ms), the time between input and output increases with the number of synapses introduced into the circuit. As an... 

Pharmacology The precise mechanism of action is not known. Baclofen can inhibit mono- and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites also may contribute to its clinical effect. Baclofen has CNS-depressant properties. 

Baclofen appears to affect the neuromuscular axis by acting directly on sensory afferents, y-motor neurons, and collateral neurons in the spinal cord to inhibit both monosynaptic and polysynaptic reflexes. The principal effect is to reduce the release of excitatory neurotransmitters by activation of presynaptic GABAg receptors. This seems to involve a G protein and second-messenger link that either increases K+ conductance or decreases Ca conductance. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

Benzodiazepines have the capacity to depress polysynaptic reflexes and have been shown to decrease decerebrate rigidity in cats and spasticity in patients with cerebral palsy. What is not clear is whether they can, in humans, relax voluntary muscles in doses that do not cause considerable central nervous system depression. Nevertheless, benzodiazepines, such as diazepam, are often prescribed for patients who have muscle spasms and pain as a result of injury. In these circumstances, the sedative and anxiolytic properties of the drug also may promote relaxation and relieve tension associated with the condition. 

Tizanidine is an a -adrenergic receptor agonist at supraspinal and spinal levels. This effect results in inhibition of spinal polysynaptic reflex activity. It presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. Tizanidine has no direct effect on skeletal muscle, the neuromuscular junction or on monosynaptic reflex activity. 

It is beta-4 (chlorophenyl)-gamma aminobutyric acid. It is a powerful neuronal depressant. It reduces the release of excitatory transmitter and is antinociceptive in animal studies. It inhibits monosynaptic and polysynaptic reflex transmission at spinal level, probably by stimulating the GABAg... 

Some sedative-hypnotics, particularly members of the carbamate (eg, meprobamate) and benzodiazepine groups, exert inhibitory effects on polysynaptic reflexes and internuncial transmission and at high doses may also depress transmission at the skeletal neuromuscular junction. Somewhat selective actions of this type that lead to muscle relaxation can be readily demonstrated in animals and have led to claims of usefulness for relaxing contracted voluntary muscle in muscle spasm (see Clinical Pharmacology). Muscle relaxation is not a characteristic action of zolpidem, zaleplon, and eszopiclone. 

Tizanidine (Zanaflex) is classified as an alpha-2 adrenergic agonist, meaning that this drug binds selectively to the alpha-2 receptors in the CNS and stimulates them. Alpha-2 receptors are found at various locations in the brain and spinal cord, including the presynaptic and postsynaptic membranes of spinal interneurons that control alpha motor neuron excitability. Stimulation of these alpha-2 receptors inhibits the firing of interneurons that relay information to the alpha motor neuron that is, interneurons that comprise polysynaptic reflex arcs within the spinal cord.27 Tizanidine appears to bind to receptors on spinal interneurons, decrease the release of excitatory neurotransmitters from their presynaptic terminals (presynaptic inhibition), and decrease the excitability of the postsynaptic neuron (postsynaptic inhibition).40 Inhibition of spinal interneurons results in decreased excitatory input onto the alpha motor neuron, with a subsequent decrease in spasticity of the skeletal muscle supplied by that neuron. 

Moruzzi (9) already clearly dissociated activation from arousal. Stimulation from the sensory terminals leads to monosynaptic and more often polysynaptic reflexes. These polysynaptic reflexes relay in subcortical structures. Depending on the intensity of stimulation, the degree of neuronal recruitment, and so forth, the number of brain structures involved will vary. Stimulation may affect the thalamus, basal forebrain, and a newly recognized loop called the cor-ticothalamocortical loop (10). 

However, activation of the central nervous system (CNS) does not equate with EEG arousals or awakenings. CNS activation implies that integrative neurons were activated and sent information to descending pathways, the nucleus tractus solitarius, and sympathetic controlling cells. An ANS modulation is always associated with an efferent response. CNS activation may lead to an arousal, an awakening, or an important ANS activity change, but activation may be limited to a polysynaptic reflex response with ANS change and no EEG arousal (6). 

Diazepam, the most commonly used benzodiazepine in equine medicine, is used as a component of anesthetic protocols (see Ch. 15) and for the treatment of seizures (see Ch. 9). It induces skeletal muscle relaxation by facilitating the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the central nervous system. It acts primarily within the spinal cord and exerts inhibitory effects on polysynaptic reflexes and intemuncial neuron transmission. 

While the regional distribution is fairly uniform for these two substances, there may be significant differences in the concentrations of aspartate and glutamate in certain areas of the spinal cord. Furthermore, biochemical studies have suggested that aspartate may be concentrated in the Interneurons of the polysynaptic reflex arc, and that there may be a specific glutamate pathway from the cortex to the corpus striatum. 

FIGURE 29 Baclofen, a skeletal muscle relaxant, acts at the spinal cord level to inhibit transmission of monosynaptic and polysynaptic reflexes. 

The names and formulae of some of the psycholeptic compounds which cannot be classified in the major chemical categories so far considered are set out in Table 5.3. Meprobamate VIII) was one of the earliest used tranquillizers. It was developed from mephenesin VII), which was introduced as a muscle relaxant and was soon seen to have a sedative action too. In small doses, meprobamate is a sedative. In larger doses, it causes muscle relaxation and has been classed, with similar compounds, as a tranquillo-sedative . Like the barbiturates, it produces no sign of extrapyramidal or central autonomic stimulation. Well-authenticated reports of addiction to meprobamate have appeared . Both mephenesin and meprobamate produce muscle relaxation by inhibiting interneurones—and hence polysynaptic reflexes—in the spinal cord. Though not described as a hypnotic, meprobamate has been successfully used in the treatment of insomnia, perhaps because it reduces tension. 

B. Drugs Used for Acute Muscle Spasm Many drugs are promoted for the treatment of acute spasm due to muscle injury. Most of these drugs are sedatives or act in the brain stem or spinal cord. Cyclobenzaprine, a typical member of this group, is believed to act in the brain stem, possibly by interfering with polysynaptic reflexes that maintain skeletal muscle tone. The drug is active by the oral route and has marked sedative and antimuscarinic actions. Cyclobenzaprine may cause confusion and visual hallucinations in some patients. It is not effective in muscle spasm due to cerebral palsy or spinal cord injury. 

It acts by inhibiting the polysynaptic reflexes both within the spinal cord and subcortical regions of the brain. It has been observed that more than 90% of it gets glucuronidated in the liver. The elimination half-life is about 60 minutes and the absorption time is from 3 to 4 hour. 

Feedback Mechanism Visual perception Haptic perception Polysynaptic reflexes Monosynaptic reflexes... 

As an alpha-2 agonist, tizanidine decreases presynaptic excitatory neurotransmitter release and postsyn-aptic neurotransmitter effectiveness. Alpha-2 receptor agonists attenuate monosynaptic and polysynaptic reflexes in the spinal cord [25]. Tizanidine decreases excitatory neurotransmitter release and Substance P release from small sensory afferents [28]. Tizanidine decreases locus coeruleus activity, thereby modulating descending motor regulatory pathways [28]. Tizanidine decreases activity of both alpha and gamma motor neurons [28]. 

Although the exact mechanism of action is not completely known, it is thought to bind to presynaptic and postsynaptic GABA-B receptors. Baclofen works mainly at the spinal cord level to inhibit monosynaptic and polysynaptic reflexes by interfering with the release of excitatory neurotransmitters. Activity at supraspinal sites may also contribute to its clinical effect. 

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