Neurons afferent

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

This is an unconventional reflex mediated by capsaicin-sensitive primary afferent neurons. In fact, an adequate stimulus can directly excite a peripheral terminal... 

Diuretics This indicates the unique property of capsaicin-sensitive primary afferent neurons to release mediators (neuropeptides and others) from both peripheral and central nervous system terminals upon adequate stimulation. Capsaicin and other chemical (protons) or physical (heat) stimuli release mediators from both peripheral and... 

In the gastrointestinal tract, drugs or toxins, as well as mechanical stimulation, induce emesis by activation of sensory receptors on afferent neurons in the vagus and sympathetic nerves. Information is relayed to the vomiting centre via the nucleus tractus solitarius... 

Substance P is a member of a group of polypeptides known as neurokinins or tachykinins. It is thought to be the primary neurotransmitter for the transfer of sensory information from the periphery to the spinal cord and brain. Substance P as well as neurokinin NKX receptors has been detected in vagal afferent neurons in the area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus. Substance P has been shown to increase the firing rate of neurons in the area postrema and nucleus tractus solitarius and to produce retching when applied directly to these areas in animal studies. 

Without interruption, the neurochemicals ultimately lead to a firing of the unmyelinated or thinly myelinated afferent neurons. This sends messages along the pain pathway in the periphery and transfers the pain message to the central nervous... 

GABAergic presynaptic inhibition of excitatory transmission of primary afferent neurones of the spinal cord resulting in epileptiform convulsions, myosis, and dyspnea with more or less prolonged apnea. 

Many different types of sensory receptors are located throughout the body. These receptors monitor the status of the internal environment or that of the surroundings. Sensory receptors are sensitive to specific types of stimuli and measure the value of a physiological variable. For example, arterial baroreceptors measure blood pressure and chemoreceptors measure the oxygen and carbon dioxide content of the blood. The information detected by these sensors then travels by way of afferent neuronal pathways to the central nervous system (CNS). The CNS is the integrative portion of the nervous system and consists of the (1) brain and the (2) spinal cord. 

Distinguish among the three types of neurons afferent neurons, efferent neurons, and interneurons... 

Afferent neurons lie predominantly in the PNS (see Figure 6.1). Each has a sensory receptor activated by a particular type of stimulus, a cell body located adjacent to the spinal cord, and an axon. The peripheral axon extends from the receptor to the cell body and the central axon continues from the cell body into the spinal cord. Efferent neurons also lie predominantly in the PNS. In this case, the cell bodies are found in the CNS in the spinal cord or brainstem and the axons extend out into the periphery of the body where they innervate the effector tissues. By way of convergence, the centrally located cell bodies may receive inputs from several different regions of the brain that will influence their activity. 

Figure 6.1 Types of neurons. Afferent neurons, which transmit impulses toward the CNS and efferent neurons, which transmit impulses away from the CNS, lie predominantly in the peripheral nervous system. Intemeurons, which process sensory input and coordinate motor responses, lie entirely within the central nervous system.

Figure 7.1 Cross-sectional view of the spinal cord. In contrast to the brain, the gray matter of the spinal cord is located internally, surrounded by the white matter. The gray matter consists of nerve cell bodies and unmyelinated intemeuron fibers. This component of the spinal cord is divided into three regions the dorsal, lateral, and ventral horns. The white matter consists of bundles of myelinated axons of neurons, or tracts. Each segment of the spinal cord gives rise to a pair of spinal nerves containing afferent and efferent neurons. Afferent neurons enter the spinal cord through the dorsal root and efferent neurons exit it through the ventral root.

The cell bodies of second-order sensory neurons are found in the dorsal horn. These neurons receive input from afferent neurons (first-order sensory neurons) entering the CNS from the periphery of the body through the dorsal... 

Afferent neurons that transmit sensory information toward the spinal cord are referred to as first-order sensory neurons. The cell bodies of these neurons are found in the dorsal root ganglia. These ganglia form a swelling in each of the dorsal roots just outside the spinal cord. The portion of the axon between the distal receptor and the cell body is referred to as the peripheral axon and the portion of the axon between the cell body and the axon terminal within the CNS is referred to as the central axon. 

As discussed, the first-order neuron is the afferent neuron that transmits impulses from a peripheral receptor toward the CNS. Its cell body is located in the dorsal root ganglion. This neuron synapses with the second-order neuron whose cell body is located in the dorsal horn of the spinal cord or in the medulla of the brainstem. The second-order neuron travels upward and synapses with the third-order neuron, whose cell body is located in the thalamus. Limited processing of sensory information takes place in the thalamus. Finally, the third-order neuron travels upward and terminates in the somatosensory cortex where more complex, cortical processing begins. 

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 example of the mechanism of the withdrawal reflex is illustrated in Figure 7.4. When a painful stimulus activates a sensory receptor on the right foot, action potentials are transmitted along the afferent neuron to the spinal cord. By way of divergence, this neuron synapses with several other neurons within the gray matter of the spinal cord ... 

Two types of afferent neurons are associated with nociceptors ... 

Figure 8.3 Referred pain. The mechanism of referred pain involves convergence of visceral afferent neurons and cutaneous afferent neurons with the same second-order neurons in the dorsal horn of the spinal cord. In this example, the pain of angina that originates in the heart is referred to the left arm.

Each sensory afferent neuron connects with an interneuron or accessory neuron. These interneurons are located entirely within the CNS, with the majority occurring in the cerebral cortex. They form numerous interconnections and are the means by which all cognitive information, thoughts and feelings, are processed. It should be emphasised that the main role of this processing of information is inhibitory. The sensory receptors provide the CNS with a massive amount of data. The interneurons process and filter this into a limited amount of useful and important informa tion. Conscious information processing forms just one part of this activity. A great deal of brain activity is concerned with routine processes, which continue without conscious awareness. 

Sensory afferent neuron Synapse Synapse Motor efferent neuron... 

Figure 1.13 Communication to and from the cardiovascular centre in the brain. The cardiovascular centre controls changes in the output from the heart (cardiac output) and the flow of blood through peripheral b ssues and organs. It is the efferent neurones that transfer informab on from the brain to the heart and peripheral vessels. The afferent neurones transfer informab on from the heart and other b ssues, e.g. muscle, to the centre. Informab on transfers from the major arteries, the coronary arteries and peripheral muscles to the brain. There is also informab on transfer within the brain and within the muscle.

Atropine can be useful in patients with carotid sinus syncope. This condition results from excessive activity of afferent neurons whose stretch receptors are in the carotid sinus. By reflex mechanisms, this excessive afferent input to the medulla oblongata causes pronounced bradycardia, which is reversible by atropine. 

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

Schematic diagram of a primary afferent neuron mediating pain, its synapse with a secondary afferent in the spinal cord, and the targets for local pain control. The primary afferent neuron cell body is not shown. At least three nociceptors are recognized acid, injury, and heat receptors. The nerve ending also bears opioid receptors, which can inhibit action potential generation. The axon bears sodium channels and potassium channels (not shown), which are essential for action potential propagation. Synaptic transmission involves release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron. Alpha2 adrenoceptors and opioid receptors modulate the transmission process.

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

Yoshimura, N. and de Groat, W. C. Increased excitability of afferent neurones innervating rat urinary bladder after chronic bladder inflammation, The Journal of Neuroscience 1999, 19, 4644-4653. 

Following inflammation there is a 10-fold increase in axons expressing AMPA or kainate receptors (Coggeshall and Carlton, 1999). In anaesthetized rats, antagonism of AMPA/kainate receptors inhibits dorsal horn neuronal responses induced by innocuous and noxious mechanical stimulation of a chronically inflamed ankle (Neugebauer et al., 1994). Application of kainate to the rat hindpaw induces activation of primary afferent neurons, an effect that is reduced by the AMPA/kainate antagonist DNQX (Ault and Hildebrand, 1993). 

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