Presented by:Kritika Sarkar

B.D.S. Final year

Neurophysiology

Neuro- anatomy The neuron.

Definition. Classification. Structure of sensory neuron.

The configuration of neurons.

Electrophysiology of nerve conduction. Electrochemistry of nerve conduction. Resting potential. Membrane excitation:

Depolarization. Repolarization.

Impulse propagation. Impulse spread.

Unmyelinated nerves. Myelinated nerves.

Physiology of peripheral nerves.

Contents

Pain.Definition.Theories.Physiology (Pathway).Mediators.Receptors.

Contents:

It is the structural & functional unit of the nervous system.

It transmits messages b/w the CNS and all parts of the body.

The neuron/nerve cell

Depending upon the function:Sensory (afferent)Motor (efferent).Relay (Interneuron).

Depending upon number of poles:Unipolar neurons.Bipolar neurons.Multipolar neurons.

Depending upon the length of axon:Golgi type I.Golgi type II.

Classification

Sensory neuron They are capable of transmitting

pain & consist of 3 main parts.

1. Dendritic zone-most distal segment, respond to stimulation, provoking an impulse centrally in the axon.

2. Axon-thin cable like structure which has similar arborizations like that of the dendrites. They may be quite long (giant squid axon measures 100-200 cm)

3. Cell body-it is located away from the axon/the main pathway of impulse transmission in the nerve. Its main function is to provide vital metabolic support.

Axon is the long cylinder of neural cytoplasm (axoplasm) encased in a thin sheath, the nerve membrane (axolemma).

The axoplasm, a gelatinous substance, is separated from extracellular fluids by continuous nerve membrane.

In some nerves this membrane is itself covered by an insulating lipid rich layer of myelin.

The membrane consists of bi-lipid layer of phospholipids, associated proteins, lipids & carbohydrates.

The lipids are oriented with their hydrophilic/polar ends facing the outer surface & the hydrophobic/non-polar ends projecting in the middle of the membrane.

Configuration of neurons

• Proteins are visualized as the primary organizational elements of membranes.

• They are classified as:• Transport proteins (channels, carriers or

pumps)• Receptor sites.

• Channel proteins are thought to be continuous pores through the membrane, allowing some ions (Na+, K+, Ca++) to flow passively, whereas other channels are “gated”, permitting ion flow only when the gate is “open”.

• Some nerves are covered with lipid layer of myelin.

• The Myelinated nerve fibers are enclosed in spirally wrapped layers of lipoprotein myelin sheaths, which are actually a specialized form of Schwann cell.

• There are constrictions at regular intervals (approx. 0.5-0.3 mm) along the myelinated nerve fibers- NODES OF RANVIER.

The function of the nerve is to carry messages in the form of electrical action potentials, which are called impulses.

Action potentials are transient depolarization of

the membrane that result from a brief increase in the permeability of the membrane to sodium, & usually also from a delayed increase in the permeability to potassium.

Physiology of peripheral nerves

Electrophysiology of nerve conduction

Resting potential

Stimulus

Slow Depolarization (0.3 msec)

Rapid Repolarization (0.7 msec)

Resting potential

Resting state- in its resting state the nerve membrane is: Slightly permeable to Na+ [Na+ migrates

inwardly because both the concentration(greater outside) & the electrostatic gradient favor such migration. Resting membrane is relatively impermeable to Na+ prevents massive influx of the ion.]

Freely permeable to K+ [It remains in the axoplasm, despite its concentration gradient, because the negative charge of the nerve membrane restrains the positively charged ions by electrostatic attraction.]

Electrochemistry of nerve conduction

Excitation of a nerve segment leads to an increase in permeability of the cell membrane to sodium ions.

The rapid influx of sodium ions to the interior of the nerve cell causes depolarization of the nerve membrane from its resting level to its firing threshold of approximately -50 to -60 mV.

A minimum 15 mV voltage potential is required to generate an action potential.

Depolarization

Firing threshold – the magnitude of the decrease in negative transmembrane potential that is necessary to initiate an action potential (impulse).

The action potential is terminated when the membrane repolarized.

This is caused by the extinction of increased permeability to Na+.

In many cells permeability to K+ increases, resulting in influx of K+, & leading to a more rapid membrane repolarization & return to its resting potential.

Repolarization

Na+ diffuses into the cell and K+ diffuses out of the cell

BUT, membrane is 75x’s more permeable to K+ than Na+ Thus, more K+ diffuses out than Na+ diffuses inThis increases the number of positive charges on the outside of the membrane relative to the inside.

BUT, the Na+-K+ pump carries 3 Na+ out for every 2 K+ in.

•Number of charged molecules and ions inside and outside cell nearly equal

concentration of K+ higher inside than outside cell, Na+ higher outside than inside.

•Potential difference: unequal distribution of charge exists between the immediate inside and immediate outside of the plasma membrane: -70 to -90 mV.

Resting potential

A stimulus excites the nerve, leading to the following sequence of events:

A. An initial phase of slow depolarization. The electrical potential within the nerve becomes slightly less negative.

B. When the falling electrical potential reaches a critical level, an extremely rapid phase of repolarization results. This is termed as threshold potential, or firing threshold.

C. This phase of rapid depolarization results in a reversal of the electrical potential across the nerve membrane. The interior of the nerve is now electrically positive in relation to the exterior. An electrical potential of +40 mV exists on the interior of the nerve cell.

Step I

After these steps of depolarization, repolarization occurs.

The electrical potential gradually becomes more negative inside the nerve cell relative to outside until the original resting potential of -70mV is again achieved.

The entire process requires 1 millisecond : Depolarization=0.3 msec. Repolarization=0.7 msec.

Step II

Stimuli Disruption of RMP

Cell’s interior: -ve

to +ve

Cell’s exterior:

+ve to –ve

Production of local current

Current flows from depolarized

to resting segment

Transmembrane

potential ß

Action potential in the next segment

Carried on……

Impulse SpreadIn myelinated & un-myelinated nerve fibers.

Fiber class

Subclass

Myelin

Function

A a + Motor, propioception

b + Motor, propioception

g + Muscle tone

d + Pain, temperature, touch

B + Various autonomic functions

C sC - Various autonomic functions

d gC - Various autonomic functions; pain, temperature, touch

Classification of peripheral nerve fibers

Pain

An unpleasant emotional experience usually initiated by a noxious stimulus & transmitted over a specialized neural network to the CNS where it is interpreted as such.

Definition

Theories

Classical description was provided by Descartes in 1644, when he conceived pain system as a straight through channel from skin to the brain.

The concept changed little until 19th century when Muller postulated the theory of information transmission only by the way of sensory nerves.

Von Frey developed the concept of specific cutaneous receptors for the mediation of touch, heat, cold & pain.

Free nerve endings were implicated as pain receptors. A pain centre was thought to exist within the brain, which

was responsible for the development of all overt manifestations of the unpleasant experience.

Specificity theory

In 1894 Goldscheider was the 1st to propose that stimulus intensity & central summation are the critical determinants of pain.

The theory suggested that particular patterns of nerve impulses that evoke pain are produced by summation of sensory input within the dorsal horn of the spinal column.

Pain results when the total output of cells exceeds a critical level.

For example, touch plus pressure plus heat might add up in such a manner that pain was the modality experienced.

Pattern theory

The gate control theory, proposed by Melzack & Wall in 1965 & recently reevaluated, is presently receiving considerable attention.

Although the theory may be simply stated, its ramifications are extremely complex.

The gate control theory postulates:1. Information about the presence of injury is transmitted to the CNS by

small peripheral nerves.2. Cells in the spinal cord or nucleus of 5th cranial nerve, which are excited

by these injury signals, are also facilitated or inhibited by other large peripheral nerves that also carry information about innocuous events.

3. Descending control systems originating in the brain modulate the excitability of cells that transmit information about injury.

Therefore the brain receives messages about injury by the way of the gate control system, which is influenced by:

1. Injury signals.2. Other types of afferent impulses &3. Descending control.

Gate control theory

Agents that Activate or Sensitize Nociceptors:

Arachidonic acid

Cell injury

Prostaglandins

Leukotrienes

• vascular permeability.

• sensitizes nociceptor

Cyclooxygenase pathway

Cell injury tissue acidity Kallikrein Bradykinin vascular permeability

activates nociceptor

synthesis & release of prostaglandins

Substance P (released by free nerve endings) sensitize nociceptor

vascular perm., plasma extravasation

(neurogenic inflammation)

releases histamine (from mast cells)

Calcitonin gene related peptide (free nerve endings) dilation of peripheral capillaries

Serotonin (released from platelets & damaged endothelial cells) activates nociceptor

Cell injury potassium activates nociceptor.

Pain ReceptorsSensory nerve endings that mediate pain (nociceptor) are

actually chemo receptors. It is currently believed that there are both mechano-receptive & chemo-receptive nociceptors.

Criteria for a substance to be classified as a chemical pain mediator are: General accessibility & activation as a consequence of injury,

infection or mechanical tissue damage. Suppression of mediator formation resulting in prevention of

pain fiber activation. Easy formation from labile precursors, release from sensitive

storage sites, and short half-life. Pain caused by exogenous application onto nociceptors.

All criteria are met within the dental pulp by the peptide, substance P. In other parts, other chemical agents are significant, with bradykinin being one of the most active.

Monheim’s Local anesthesia & pain control in dental practice (7th edition).

Malamed’s Handbook of local anesthesia. Ganong’s review of Medical physiology. Textbook of medical physiology by Guyton & Hall. www.iasp-pain.org www.google.com www.bioalive.com www.ncbi.org www.wikipedia.org www.slideshare.net

Bibliography

Thank you!