INTRODUCTION to LOCAL ANESTHESIA

and NEUROPHYSIOLOGY

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Dr.Mohammad. M.Abu.Mowais
DDS, MSc, Palestinian board in oral surgery

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Definition of Local Anesthesia
a loss of sensation in a circumscribed area of
the body caused by a depression of excitation
in nerve endings
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Or

an inhibition of the conduction process in

peripheral nerves; no loss of consciousness
occurs
 Properties of Local Anesthetics:
1) Not irritating to the tissue
2) No permanent alteration of nerve structure
3) Systemic toxicity should be low
4) Effective whether injected or applied topically
5) Time of onset of anesthesia should be as short as possible
6) Duration of action must be long enough to complete the procedure
but not so long as to require an extended recovery
7) Should be stable in solution and easily biotransformed
8) Should not cause allergic reactions
9) Should be sterile or capable of being sterilized by use of heat
 Neurophysiology
The Neuron
• The neuron is the structural unit of the nerve

• Two types of neurons

1) Sensory afferent (toward the CNS)
2) Motor efferent (away from the CNS)
Sensory Neurons: transmit pain; three parts
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1) Dendritic Zone- free nerve endings;
most distal portion of the neuron

2) Axon- synapses with the CNS to transmit

input to the brain

3) Cell Body- provides metabolic support for

the entire neuron I JI
Sensory Neurons (afferent)
Motor Neuron (efferent)
 The Axon

✔long cylinder of neural cytoplasm (axoplasm) encased in a

thin sheath, the nerve membrane, or axolemma
✔axoplasm is a gelatinous substance that is separated from
extracellular fluids by a continuous nerve membrane
 have a fiber have
gates like Na K
that have effect on
action potential

✔nerve cell membrane is ~75 Angstroms thick

✔all cell membranes are organized to block the diffusion of water
soluble molecules
✔all cell membranes are selectively permeable via specialized pores
✔transduce information by protein receptors responsive to chemical or
physical stimulation by neurotransmitters, hormones, light, vibrations
 The Membrane

✔cell membrane is a bilipid layer of phospholipids

✔hydrophilic (polar) ends facing the outer surface and
hydrophobic (nonpolar) ends projecting to the middle of
the membrane
 the nerve membrane lies at the
interface between the
extracellular fluid and the axoplasm

the nerve membrane separates highly

ionic concentrations within the axon
from those outside
The Membrane: Lipid Layer
 IS 96 The Membrane
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the resting nerve membrane has an electrical resistance about 50
times greater than that of the extra/intracellular fluids, thus preventing
the passage of Na, K and Cl ions down their concentration gradients

when a nerve impulse passes, electrical conductivity of the nerve

membrane increases 100-fold: increased conductivity allows the
passage of Na and K ions down their concentration gradient through
the nerve membrane membrane Im impuleme a
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movement of these ions provides the energy for impulse conduction
along the nerve

some nerve fibers are covered in myelin, specialized Schwann cells

regular interval constrictions are called Nodes of
Ranvier which form gaps between two adjoining
Schwann cells
 uh P neuron 161
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Electrophysiology of Nerve Conduction

• Nerve resting potential is -70 mV; this is

produced by differing concentrations of ions
on either side of the nerve membrane

• Interior of the nerve is negative compared to

the exterior before a stimulus excites the nerve
STEP 1 - Stimulus excites nerve which leads to:
70 resting
1) Slow Depolarization- inside of nerve becomes
less negative 60 50

2) Threshold Potential- extremely rapid

depolarization occurs from the falling electrical
potential so

3) Rapid Depolarization- interior is electrically

positive +40 mV and the outside is negative
(-70 mv) 50 40
Resting to Threshold Potential

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Threshold Potential to Rapid
Depolarization
 STEP 2 - after depolarization,
repolarization occurs

Repolarization- electric potential

inside the cell gradually becomes
more negative until the interior is
again restored to –70 mV
Depolarization Repolarization
 Depolarization ITA
0.03ms

-excitation leads to increase in permeability of the

cell membrane to sodium ions Na

-transient widening of transmembrane ion channels

allow passage of the sodium ions

-rapid influx of sodium ions into the interior of the

nerve cell causes depolarization of the cell
membrane from resting to firing threshold which is
-50 to -60 mV
Firing Threshold magnitude of the
decrease in negative trans-membrane
potential that is necessary to initiate an
action potential (impulse); getting more
positive with more influx of Na+
Firing Threshold
-decrease in negative transmembrane potential of
+15 mV; from –70 mV to –55 mV is necessary to
reach the firing threshold; voltage differences of
less than +15 mV will not induce firing

-exposure to a nerve with local anesthetic raises its

firing threshold

-elevating the firing threshold means that more

sodium must pass through the membrane to
decrease the negative transmembrane potential
to a level where depolarization occurs
 -when the firing threshold is reached,
sodium rapidly enters the axoplasm due to
increased membrane permeability

-depolarization lasts ~ .3 msec

 Repolarization
The action potential is terminated when
the membrane repolarizes; this is caused
by the inactivation of increased
permeability to sodium

The movement of Na+ and K+ during

depolarization is passive
Repolarization
After the membrane potential returns to –70 mV
there is still a slight amount of excess sodium
within the nerve cell and a slight excess of
potassium extracellularly

Sodium is moved out of the cell using ATP and

the sodium pump

Repolarization requires ~ .7 msec

Absolute Refractory Period the nerve
is unable to respond to another stimulus
regardless of its strength

Relative Refractory Period a new

impulse can be initiated at this time but
only by a stronger than normal stimulus;
follows the absolute refractory period
 Membrane Channels
Sodium channels line the excitable nerve membrane which
are lipoglycoproteins situated firmly in the membranes
Sodium passes through the channels 12 times easier than
potassium
Sodium ions are “thinner” than potassium or chloride ions
and should therefore move easily down concentration
gradients through membrane channels into the nerve cell,
however:

However, sodium ions are hydrated at rest and increase in

size to 3.4 Angstroms; they are too large to pass through the
sodium channels when the nerve is at rest
Membrane Channels
 Membrane Channels

Potassium and chloride can pass through these gated

channels

During depolarization the gated transmembrane sodium

channels change their configuration to allow the sodium
ions to enter the cell
 Impulse Propagation

Activation of an action potential by a stimulus

Disruption of the resting nerve membrane potential

Interior of the cell goes from negative (–70 mV) to positive (+40 mV)

Exterior of the cell changes from positive to negative

Local currents begin flowing between the depolarized segment and the
adjacent resting area

Local currents flow from positive to negative extending for several

mm along the nerve membrane

As a result, the interior of adjacent areas become less negative and the
exterior becomes less positive
Impulse Propagation
 Impulse Propagation
Transmembrane potential decreases approaching firing threshold for
depolarization

When transmembrane potential decreases by 15mV from resting

potential, firing threshold is reached and rapid depolarization occurs

The newly depolarized segment sets up local currents and it all starts
over again

Newly depolarized segments return to resting state after absolute and

relative refractory periods

Waves of depolarization can move in only one direction due to the

absolute and relative refractory periods, thus retrograde (backward)
movement is prevented
 Impulse Spread

1) Unmyelinated Nerves
-high electrical resistance cell membrane
-slow forward “creeping” spread of impulses
-conduction of unmyelinated C fibers is1.2 m/sec slowly
 2) Myelinated Nerves

-insulating myelin separates the extra/intracellular charges

-the farther apart the charges the smaller the current necessary
to charge the membrane
-current leaps from node to node saltatory conduction
 Myelinated Nerves

if conduction of an impulse is blocked at one node, the local

current skips that node and continues to the next node
 P I I
in

A minimum of 8 to 10 mm of nerve must

be covered by anesthetic solution to
ensure adequate block of impulse spread
Mode and Site of Action of Local Anesthetics

Local anesthetics interfere with the excitation process in the

nerve membrane in one or more of the following ways:

1) Altering the basic resting potential of the nerve

membrane 770

2) Altering the threshold potential (firing level)

3) Decreasing the rate of depolarization*O.IN C

4) Prolonging the rate of repolarization 0.7ms

 Because of local anesthetics, cellular
depolarization is not sufficient to
reduce the membrane potential of a
nerve fiber to its firing threshold and a
propagated action potential
does not develop
Where Do Local Anesthetics Work?

Specific Receptor Theory local anesthetics act by binding to specific receptors on the
if I'm Hild sodium channel
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the action of the drug is direct and is not mediated by some change
in the general properties of the cell membrane

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a specific receptor site for local anesthetics exists in the sodium channel which eliminates
permeability to sodium ions
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Tertiary amine local anesthetics inhibit

influx of sodium during nerve conduction
 Mechanism of Action of Local Anesthetics
1) Displacement of calcium ions from the sodium channel receptor site

2) Binding of the local anesthetic molecule to this receptor site

3) Blockade of the sodium channel

4) Decrease in sodium conductance

5) Depression of the rate of electrical depolarization

6) Failure to achieve the threshold potential level (firing level)

7) Lack of development of propagated action potentials

8) Conduction blockade
1) The nerve remains in a polarized state, therefore
there is no depolarization because the ionic
movements responsible for the action potential fail
to develop

2) The membrane’s electrical potential remains

unchanged, therefore local currents do not
develop and the self-perpetuating mechanism of
impulse propagation is stalled

3) Nerve block produced by local anesthetic is

called a nondepolarizing nerve block
 Local Anesthetic Molecules

Majority of local anesthetics are tertiary amines

(except Prilocaine) tester cause
may
allergy
All local anesthetics are amphipathic
(lipophilic/hydrophilic)
Three main parts of the local anesthetic molecule:
1) Lipophilic Part (aromatic ring)
2) Intermediate Chain (amide or ester)
3) Hydrophilic Part (ethyl alcohol/acetic)
The lipophilic part of the local anesthetic is the largest portion
of the molecule
Hydrophilic part of the local anesthetic is an amino derivative
of ethyl alcohol or acetic acid
Local anesthetics without a hydrophilic portion are not
suitable for injection but are good topical anesthetics, i.e.,
Benzocaine
9164
 What Form Do Local Anesthetics
Exist in the Cartridge?

Labs prepare local anesthetics as basic: poorly soluble

in water and unstable on exposure to air; they have
little to no clinical value in this state

Since they are weakly basic, they combine readily

with acids to form local anesthetic salts which makes
them soluble in water and stable
61 weakbase basic job
localanestheticsall 6 acid x̅ a
Local anesthetics used for injection
are dispensed as salts, most
commonly the hydrochloride salt,
dissolved in either sterile water
or saline; so in the cartridge they
are salts
 pH Variations
like inflamed tissue
Acidification of tissues decreases local anesthetic
effectiveness
Inadequate anesthesia results when local anesthetics are
injected into inflamed/infected tissues

pH of normal tissues ~ 7.4

pH of inflamed tissues ~ 5.5
Vasoconstriction
Local anesthetics containing epinephrine or other
vasopressors are acidified by the manufacturer to inhibit the
oxidation of the vasopressor
Clinically, the lower the pH the more
burning on injection slower onset of
anesthesia
II be as 0 in axoplasm It www.t
pH of the interior of the nerve remains
unchanged and stable despite wide
variations in extracellular fluid pH;
so it is with the pH of the extracellular
fluid that determines the success or
failure of local anesthetics
 Why not increase the pH of the
local anesthetic in the cartridge?

ANSWER: Because the local

anesthetic base is unstable, it would
precipitate out of alkalinized solutions
 The extracellular fluid pH is most
important when it comes to the free
base getting into the nerve sheath; if the
extracellular pH is acidic, as with an
infection, the local anesthetic can not
enter the nerve in order to do its job;
the free base state will never appear or
so few molecules will cross the nerve
membrane and inadequate anesthesia
in acid high cons of Itt will occur
bind
with AN in extrellule flebid
 Effect of decreased pH on actions of
local anesthetic

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Less free base (RN) molecules available to diffuse across nerve sheath
Block anesthesia can be successful
even in the presence of infection;
ido not inject directly into the
infection because it can be spread
throughout the connective tissue
 Dissociation of Local Anesthetics

The local anesthetic salt is dissolved in sterile water

or saline

-It exists simultaneously as:

1) uncharged molecules (free base) (RN) (Class C)
2) positively charged molecules (cation) (RNH+)
(Class D)
Dissociation of Local Anesthetics

pKa is a measure of a molecule’s

affinity for hydrogen ions (H+);
when the pH of a solution has the
same value as the pKa, 50% of the
drug exists as the free base (RNH+)
and 50% exists as the cation (RN)
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Low pH (acidic) shifts toward the
cationic form; more RNH+

High pH (basic) shifts toward the

free base form; more RN
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 The relative proportions of ionic forms
(RNH+, RN) depends on three variables:

1) pH of the local anesthetic solution

481 PH a of GIN
2) pH of the surrounding tissues
(infection or not)

3) pKa or dissociation constant of the

specific local anesthetic
higher pKa increased H+ increased Onset Time
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Bupivacaine with pKa ~8.1 will take longer to work
because there are fewer free base molecules
available to penetrate the nerve membrane

it can take up to 8 minutes at pH of 7.4 (tissue pH)

(especially with infection present)
Four Factors Are Involved In The Action of a
Local Anesthetic:
1) Diffusion of the drug through the nerve sheath

2) Binding of the drug at the receptor site in the membrane

channel

3) Free bases (RN) cross the nerve membrane

4) Cation (RNH+) blocks the receptor

The uncharged, lipid-soluble free base (RN)

form of the local anesthetic is responsible
for diffusion through the nerve membrane
 Local Anesthetics with lower pKa have large
number of free base molecules (RN) that are
able to diffuse through the nerve sheath

But the anesthetic action of this drug is

inadequate because at intracellular pH of 7.4 a
very small number of base molecules dissociate
back to the cationic form (RNH+) necessary for
binding at the receptor site
(e.g., Benzocaine = pKa 3.5)
The rate of onset is related to the pKa
of the local anesthetic

Bupivacaine at pKa 8.1 has a slower

onset than Lidocaine pKa 7.7
 Antioxidants and pH
Antioxidants are added to local anesthetics to delay the
oxidation of the vasopressor; oxidation will turn the solution a
reddish-brown

Sodium bisulfite is a common antioxidant placed in local

anesthetic solution

Lidocaine 2% with a pH of 6.8 is acidified to a pH of 4.2 with

the addition of the antioxidant sodium bisulfite

The shelf life of local anesthetics decrease as the pH of the

solutions decreases
 The large buffering capacity of the tissue
(pH 7.4) is able to maintain a normal tissue
pH, however, it takes a longer time to do so
after an injection of a pH 4.2 solution than
B with a pH 6.8 solution

the end result is a slower clinical onset of

action while the tissue pH equilibrates the
pH of the solution with the pH of the
tissues
Barriers to Diffusion of the Solution
 Induction of Local Anesthesia
Mantle Bundles (OUTSIDE)

-fasciculi that are located near the surface of the nerve

-first ones reached; exposed to higher concentration of

the solution

-blocked completely shortly after injection

-innervates more proximal regions of the nerve

(molars from IANB)
 Hot I
Time
Hect ofanesthesia
 Core Bundles (INSIDE)

-fasciculi found closer to the center of the nerve

-must delay before onset of anesthesia;

lower concentration of solution

-explains why patient may have inadequate

pulpal anesthesia in the midst of profound
soft tissue anesthesia

-innervates more distal regions of the nerve

(incisors from IANB)
 Induction Time
Factors Under Clinician’s Control:
1) Concentration of the drug
2) pH of the local anesthetic solution

Factors not Under Clinician’s Control:

1) Diffusion constant of the anesthetic drug
2) Anatomical diffusion barriers of the nerve
 What is the order of recovery from Local
Anesthetic?
Follows same diffusion patterns as induction only in the
reverse order

Mantle fibers lose anesthesia before the core fibers

Third molars would regain sensation before incisors if an

inferior alveolar nerve block were administered

Recovery is a slower process than induction because the local

anesthetic molecule is bound to the drug receptor site in the
sodium channel and is released more slowly than it is absorbed
 p ing IS
n
What if I need to re-inject a patient?
At the time of re-injection, the concentration of local
anesthetic in the mantle fibers is less than the
centrally located core fibers

The partially recovered mantle fibers still contain

some level of local anesthetic, although not enough
to provide complete anesthesia

Upon re-injection, the mantle fibers are again

subjected to a high concentration of local anesthetic
solution inward toward the nerve
-The combination of residual local anesthetic and the
newly deposited supply results in rapid onset of
profound anesthesia with a smaller volume of the
drug being administered

-Tachyphylaxis is an increased tolerance to a drug

that is administered repeatedly; this could result in
less anesthesia after re-injection