Othe local anesthetics

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Drugs classified as local anesthetics inhibit the conduction of action potentials in all afferent and efferent nerve fibers. Thus, pain and other sensations are not transmitted effectively to the brain, and motor impulses are not transmitted effectively to muscles. Local anesthetics have various clinical uses to treat acute or chronic pain or to prevent the sensation of pain during procedures. To understand the mechanism of action of the local anesthetics, an introduction to the physiology of nerve fibers and the transmission of pain sensation is briefly discussed below.

Physiology of Nerve Fibers and Neurotransmission

The nervous system functions to receive stimulation and transmit stimulus via the nerve cells or neurons. A neuron is a single cell typically composed of a cell body connected via an axon to the axon terminal (Fig. 22.7). The axon terminal is the presynaptic component of the nerve synapse and may contain neurotransmitters ready to be released upon receiving an action potential "message". The axon

Neuron cell body

Node of Ranvier

Neuron, cell membrane

Neuron cell body

Node of Ranvier

Neuron, cell membrane

Figure 22.7 • Schematic diagram of a neuron. Representation of the various branching found in dendrites.

Dendrites

Synaptic knob

Dendrites

Synaptic knob

Figure 22.7 • Schematic diagram of a neuron. Representation of the various branching found in dendrites.

Figure 22.8 • Representations of myelinated (A) and unmyelinated (B) axons.

varies in length from a few millimeters to a meter or longer. Most axons are too long to transmit the signal to the terminal ending by simple chemical diffusion. Thus, the message received by the neuron cell body is transmitted as an electrical impulse to the axon terminal. The electrical impulse is most often generated at the axon hillock, the region of the cell body where the axon emerges. The electrical impulse is conducted by changes in the electrical potential across the neural membrane. The rate at which the message is transmitted down the axon depends on the thickness of the axon and the presence or absence of myelin. The axon may be bare or it may be surrounded by the membrane of a glial cell that forms a myelin sheath (Fig. 22.8). Between the myelin sheaths are areas of the axonal membrane that are unmyelinated, these bare areas are called the nodes of Ranvier. The nodes of Ranvier allow the nerve impulse to skip from node to node down the length of the axon to increase the speed of the action potential conduction (Fig. 22.9). In unmyelinated neurons, the change in the electrical potential of one part of the membrane causes a change in electrical potential of the adjacent membrane, thus the impulse moves along the axon slower. Nerve impulses travel at speeds of up to 120 m/s in myelinated axons and 10 m/s in unmyelinated axons.

The electrical potential difference between the inner and outer surfaces of the cell membrane is a result of the movement of ions across the membrane. At rest, most neurons have a resting potential of about -70 mV. This means that the inside of the neuron contains more anionic charges than the external side. The ions that move across the nerve membrane and contribute to most of the electrochemical potential are Ca2+, Na+, K+, and Cl-. For a nerve cell to transmit an impulse, the internal charge must increase about 20 mV to -50 mV, the firing threshold for a nerve cell. If this initial depolarization reaches the firing threshold, an action potential will be generated. During an action potential the internal charge will quickly increase to about +35 mV and the membrane is now depolarized. This spike is quickly followed by the hyperpolarization of the membrane, to

Axon Direction of movement of nerve impulse-►

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