opic 11. The common characteristic of sensory systems. The somato-sensory system.

Physiology of pain sensitivity

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Physiological dictionary of the topic:

1) Absolute threshold of irritation – is the smallest level of stimulus that can be

detected, usually defined as at least half the time.
2) Differential threshold of irritation – is the minimum increase in a stimulus
required to detect a difference in the perception
3) Adaptation – Adaptation is the decline of the electric responses of a receptor
neuron over time in spite of the continued presence of an appropriate stimulus of
constant strength. This change is apparent as a gradual decrease in the frequency of
spikes generated within the receptor neuron.
4) Nociception – is the process by which noxious stimulation is communicated
through the peripheral and central nervous system. Nociceptors are specific
receptors within the skin, muscle, skeletal structures, and viscera that detect
potentially damaging stimuli
5) Proprioceptive analyzer – helps us to determine the weight of an object by the
amount of pressure or force it places through our joints. This then helps us to
develop control and apply the right amount of pressure needed to manipulate
objects.
6) Sensor fields – A device that establishes a radio frequency field in its vicinity and
detects changes in that field resulting from the movement of persons or objects within
its range.
7) Somatosensory system –The somatosensory system is the part of the sensory
system concerned with the conscious perception of touch, pressure, pain,
temperature, position, movement, and vibration, which arise from the muscles, joints,
skin, and fascia
8) Pain –An unpleasant sensory (noxious) and emotional experience associated with
actual or potential tissue damage
9) Antinoceptive system – the action or process of blocking the detection of a
painful or injurious stimulus by sensory neurons.
10) Sensory system – The sensory system is a complex neural network of pathways
that relay information about the external environment between the brain and body

The main theoretical questions of the topic:

1. The conception of sensory systems or analyzers, their structure, value

and classification
https://www.slideshare.net/whisper119/sensory-systems-1

2. The intensity of sensations. The absolute and differential thresholds of

irritation. The Weber-Fechner’s laws:
 Intensity of a sensation is directly proportional to the intensity of the
physical stimulus raised to a constant power, so it depends on the
strength of the stimulus.
 The absolute threshold of sensation is the minimum intensity of a
stimulus that is needed to detect a particular stimulus 50% of the
time, so it is the lowest level at which a stimulus can be detected.

exp:
 The minimum intensity of light we can see
 The lowest volume of a sound we can hear
 The smallest concentration of particles we can smell
 The smallest concentration of particles we can taste
 The lightest touch we can feel

 Differential threshold is the difference between two stimuli or

between one level of a stimulus and another level of that stimulus,
it is also known as “just noticeable difference” (JND), so it is the
minimal perceptible difference in strength between two stimuli.

exp:
 The smallest difference in sound for us to perceive a change in the
radio’s volume
 The minimum difference in weight for us to perceive a change between
two piles of sand
  The minimum difference of light intensity for us to perceive a difference
between two light bulbs
 The smallest difference of quantity of salt in a soup for us to perceive a
difference in taste
 The minimum difference of quantity of perfume for us to perceive a
difference in something’s smell
 The Weber-Fechner’s laws expresses the sensitivity of a sensory
system to differences between two stimuli, the higher the intensity
of a stimulus, the more it will need to change so we can notice a
difference.

3. Classification of the receptors and main properties of the receptors:

Sensory receptors convert specific forms of energy into action potentials

in sensory neurons.

Sensory receptors can be categorized in various ways:

Function:
Mechanoreceptors, Chemoreceptors, Thermoreceptors, Photoreceptors,
& Nociceptors.
Location:
Exteroreceptors, Visceroreceptors, & Proprioceptors.
Structure:
Free nerve endings, Tacile/Merkle disks, Hair follicle receptors, Pacinian
Corpuscles, Meissner corpusle, Ruffini end organs, Muscle spindles, &
Golgi tendon apparatus.

1. Function:

Cutaneous mechanoreceptors: mediate responses to touch and

pressure.

 Activated by changes in pressure

 Common mechanoreceptors include
 Pacinian corpuscles in the subcutaneous tissue
 Meissner corpuscles in non-hairy skin
 Baroreceptors in the carotid sinus
 Hair cells on the organ of Corti and in the semicircular canals

Thermoreceptors detect the sensations of warmth and cold.

  Located in the skin and includes cold and warm receptors.

Nociceptors: respond to potentially harmful stimuli such as pain,

extreme heat, and extreme cold.

 These are also in the skin.

Chemoreceptors: are stimulated by a change in the chemical

composition of the local environment. These include receptors for
taste and smell as well as visceral receptors that are
sensitive to changes in the plasma level of O2 , pH, and osmolality.

 Activated by chemicals
 They serve for olfaction and taste

Photoreceptors in the rods and cones in the retina respond to light.

 Activated by light
 Rods and cones (located in the retina)
o Rods are sensitive to low-intensity light and function better in
a dark environment
o Cones have a better threshold for light, therefore function
well in daylight. They also participate in color vision.
2. Location:

Exteroreceptors; Associated with the skin and detects the external

environment.

Visceroreceptors; Associated with the visceral organs & detects the

internal environment.

Proprioceptors; Associated with joints, tendons, & other CT & detects

body position, mvmt, & extent of stretch or force of muscular contraction.

4. The mechanisms of irritation of primary and secondary receptors:

 5. The adaptation of the receptors. The possible mechanisms of
adaptation
Adaptation is the decline of the electric responses of a receptor neuron over time in spite of
the continued presence of an appropriate stimulus of constant strength. This change is
apparent as a gradual decrease in the frequency of spikes generated within the receptor
neuron.

What causes receptor adaptation?

Brief stimulation produces adaptation which occurs and recovers while more prolonged
stimulation can produce slower and more lasting forms of adaptation. Also, repeated sensory
stimulation appears to temporarily decrease the gain of thalamocortical synaptic
transmission.
What sensory receptor adapts quickly?
The Rapidly Adapting (RA) or Meissner corpuscle end-organ mechanoreceptor (also known
as the tactile corpuscles) underlies the perception of light touch such as flutter and slip on the
skin. It adapts rapidly to changes in texture (vibrations around 50 Hz).
Sensory Adaptation occurs when sensory receptors change their sensitivity to the stimulus.
This phenomenon occurs in all senses, with the possible exception of the sense of pain.
Why do pain receptors not adapt?
Pain receptors, unlike other sensory receptors in the body, do not adapt or become less
sensitive to repeated stimulation. Under certain conditions the receptors become more
sensitive over a period of time. These substances can stimulate pain receptors or cause
direct damage to the nerve endings themselves.

Examples of Sensory Adaptation :

Sight : When you go into a dark room or outside at night, your eyes eventually adjust to the
darkness because your pupils enlarge to let in more light. Likewise, when you are in bright
light, your eyes adjust by the narrowing of your pupils. This is another form of sensory
adaptation.
How are thermoreceptors adapting to the steady state?
Temperature perception experiment. Thermoreceptors are rapidly adapting receptors, which
are divided into two types: cold and warm. When you put your finger into cold water, cold
receptors depolarize quickly, then adapt to a steady state level which is still more depolarized
than the steady-state.
Receptor adaptation mechanisms involve regulation of the number, sensitivity and
subcellular localization of receptors that detect environmental cues and convert extracellular
signals into a change of intracellular events.
How are sensory receptors adapted to their function?
The encapsulated endings such as Meissner’s and Krause’s corpuscles are fast adapting
receptors which detect the velocity and acceleration of touch stimuli. In contrast, Merkel cell–
neurite complexes are slowly adapting pressure receptors and serve to detect the velocity of
displacement.
Sensory adaptation is a change in the sensitivity of your perception of sensation
sensory adaptation :

 Tonic receptors : slow adapting : produce constant rate of firing as long as stimulus
is applied (pain)
Tonic (slow) receptors include chemoreceptors that respond to chemical levels in the blood;
pain receptors and proprioceptors do not exhibit adaptation.

 phasic receptors : fast adapting : burst of activity but quickly reduce firing rate
(adapt) if stimulus maintained
examples of receptors : NP, neuropeptide; SP, substance P; NKA, neurokinin A; CGRP,
calcitonin gene-related peptide. Slowly adapting receptors. Myelinated fibers associated with
smooth muscle of proximal airways are probably slowly adapting (pulmonary stretch)
receptors that are involved in reflex control of breathing and in the cough reflex. Rapidly
adapting receptors.

6. The conductive department of sensory systems. The conductive tracts:

specific and nonspecific information links (channels of the information
transmission):

Functions :
 conveys impulse to the cortex
 performs secondary analysis to form reflex reactions ( withdrawal
orientational reflex)
 define important information ( lateral inhibition in thalamus )

Specific ascending pathways carry single types of stimuli to the

brainstem and the thalamus, they transmit information from somatic
receptors and taste buds to the somatosensory cortex (parietal lobe), the
ones from eyes go to the visual cortex (occipital lobe), and the ones from
ears go to the auditory cortex (temporal lobe). they lead to a specific
determination regarding the site of stimulus. The only specific ascending
pathway that doesn’t pass through the thalamus is the olfactory pathway.
Nonspecific ascending pathways consist of polymodal neurons and are
activated by sensory units of several types.

a. Transmit non-specific information, in effect saying that something

happened but we don’t know what.

b. Can have many synapses

c. Typically relays through reticular formation, which is an area that
integrates input from a wide variety of sensory modalities; individual
neurons can respond to multiple sensory modalities.
d. These pathways lead to alerting responses, arousal, and can lead to
the affective (or subjective) component of a stimulus (it hurts real bad, or
it feels real good).
for us XD: Nonspecific-have convergence and notify the brain that "something" is happening,
causing general arousal and focusing attention (holy shit what was that).
Specific- the "labeled lines" that provide detailed info about the modality, location, intensity,
etc. (a hammer just hit my hand right here).

7. Structural and functional organization and functions of the

somatosensory system.
structural organization :
A somatosensory pathway will typically consist of three neurons: primary, secondary, and
tertiary.

1. In the periphery, the primary neuron is the sensory receptor that detects sensory
stimuli like touch or temperature. The cell body of the primary neuron is housed in the
dorsal root ganglion of a spinal nerve or, if sensation is in the head or neck, the
ganglia of the trigeminal or cranial nerves.
2. The secondary neuron acts as a relay and is located in either the spinal cord or the
brainstem. This neuron’s ascending axons will cross, or decussate, to the opposite
side of the spinal cord or brainstem and travel up the spinal cord to the brain, where
most will terminate in either the thalamus or the cerebellum.
3. Tertiary neurons have cell bodies in the thalamus and project to the postcentral gyrus
of the parietal lobe, forming a sensory homunculus in the case of touch. Regarding
posture, the tertiary neuron is located in the cerebellum.

functional organization :
The somatosensory system is regulated by receptors that are spread throughout the body
and measure a number of different sensory modalities in the body. These sensations can be
divided into three main divisions: external stimuli, internal stimuli, and the sense of where the
body is in space.
Perception of external stimuli can include the sense of touch (via mechanoreceptors), pain
(via nociceptors), and temperature (via thermal receptors). Perception of internal stimuli can
include organ (visceral) sensation and pain (via multiple receptor types) and blood chemical
composition (via chemoreceptors). Finally, proprioception (via proprioceptors) is the sense of
where the body is in space. The ability of an individual to touch their nose easily while their
eyes are closed is an example of the proprioception system.
functions :
The role of somatosensory systems is to provide sensory feedback to the central nervous
system continuously.
The somatosensory system is a network of neurons that help humans recognize objects,
discriminate textures, generate sensory-motor feedback and exchange social cues.
The somatosensory system functions in the body’s periphery, spinal cord, and the brain.

 Periphery: Sensory receptors (i.e., thermoreceptors, mechanoreceptors, etc.) detect

the various stimuli so they relay peripheral sensations such as pain, pressure,
movement or temperature from the skin to the brain.
 Spinal cord: Afferent pathways in the spinal cord serve to pass information from the
periphery and the rest of the body to the brain.
 Brain: The postcentral gyrus contains Brodmann areas (BA) 3a, 3b, 1, and 2 that
make up the somatosensory cortex. BA3a is involved with the sense of relative
position of neighboring body parts and the amount of effort being used during
movement. BA3b is responsible for distributing somatosensory information to BA1
and shape and size information to BA2.

8. Cortex department of sensory system: analysis and synthesis of

afferent irritations. The interactions between sensory systems:

A single afferent neuron with all its receptor endings makes a sensory
unit. When stimulated, this is the portion of the body that leads to activity
in a particular afferent neuron is called the receptive field of that neuron.
Afferent neurons enter the CNS, diverge and synapse upon many
interneurons. These afferent neurons are called sensory or ascending
pathways and specific ascending pathways if they carry information
about a single type of stimulus. The ascending pathways reach the
cerebral cortex on the side opposite to where their sensory receptors are
located.
Specific ascending pathways that transmit information from somatic
receptors and taste buds go to the somatosensory cortex (parietal lobe),
the ones from eyes go to the visual cortex (occipital lobe), and the ones
from ears go to the auditory cortex (temporal lobe).
Olfaction is NOT represented in the cerebral cortex.
Nonspecific ascending pathways consist of polymodal neurons and are
activated by sensory units of several types. These pathways are
important in alertness and arousal.
Cortical association areas, lying outside primary cortical sensory areas,
participate in a more complex analysis of incoming information such as
comparison, memory, language, motivation, emotion, etc.
The interactions between sensory systems:
Each sensory system sends signals to the brain. It's up to the brain to
interpret these signals and come up with a response. To do this, the
brain uses sensory integration which is a combination of information from
multiple sensory systems.
Sensory signals first enter the brain through the thalamus (except for
olfaction, which bypasses this area). From there, it is routed to a sense-
specific area of the cortex. Cortical areas, in turn, send signals to the
brain's "association areas," which combine information from multiple
senses.
Some examples of how the human senses interact:
Example 1: Smell and taste
When eating food, the experience of eating involves being able to both
taste and smell the food that is being eaten. A pizza does not just taste
good because it is sensed by taste buds on the tongue. Smells of cooked
dough, cheese, and the different toppings are just as important as taste
in the process of savoring food that is eaten.
Example 2: Vision and touch
Being able to solve a puzzle requires picking up and touching puzzle
pieces as well as looking for visual clues about which pieces might fit
together.
Example 3: Sight, sound, and touch
When someone crosses a busy street, multiple senses are involved. A
person will look at traffic lights, other pedestrians, and the movement of
cars. They will also listen for the sound of honking horns or rushing cars
and feel vibrations from traffic on the ground.

9. Nociception, the physiological characteristic of nociceptors

Nociception :
Nociception is a subcategory of somatosensation. It is the neural processes of encoding and
processing noxious stimuli, it refers to a signal arriving at the CNS as a result of the
stimulation of specialized sensory receptors in the peripheral nervous system called
nociceptors.
Nociception is the measurable physiological response of specialized sensory receptors
(nociceptors) to overt or potential tissue damage and is perceived in the CNS—via the
spinothalamic tract, the thalamus, and finally different areas in the neocortex—as pain.
Initially, noxious chemical, mechanical, or thermal stimuli are detected at nerve endings of
primary sensory neurons with their soma located in the dorsal root ganglion (DRG) for body
sensation, and in the trigeminal ganglion (gasserian ganglion) for face sensation. Specialized
receptors () located at the cell membrane of sensory nerve endings translate the intensity of
a given stimulus into action potential frequency, which results in the emission of glutamate
and peptides in the respective area in the spinal cord dorsal horn (mostly superficial laminae
I and II with some projections to lamina V).

characteristic of nociceptors :
they have the morphological appearance of free nerve endings
nociceptors are non adapting receptors
Nociceptors are characterized by two distinctive features:
 they are responsive preferentially to tissue threatening stimuli and encode their
intensity,
 They mediate nocifensive motor and vegetative reactions by their central
connections.

10. The structure-functional characteristic of a nociceptive system. The conductive pathways

and levels of nociceptive information processing. The mechanisms of forming the pain
Pain pathway physiology- Dr. Anil babu Swarna (slideshare.net)

The structure-functional characteristic of a nociceptive system :

The conductive pathways and levels of nociceptive information processing :

the nociceptive pathway is an efferent three neuron dual ascending system ( exemple ;
anterolateral and dorsal column medial lemniscal pathways ) with descending modulation
from the cortex , thalamus and brainstem
the first order neurons :
The first order neurons that make up the dual ascending system have their origins in the
periphery as A delta and polymodal C fibers . first order neurons synapse on second order
neurons in the dorsal horn primarily with laminas where they release excitatory amino acids
and neuropeptides

Mechanism
Nociceptive stimuli activate TRP channels located on nerve endings, which cause first-order
neurons to depolarize and fire action potentials. Action potential frequency determines
stimulus intensity. A delta fibers release glutamate onto second-order neurons, while C fibers
release neuropeptide neurotransmitters. First-order neurons are found in the dorsal root
ganglion (stimulus from the body) and trigeminal ganglia (stimulus from the face). A delta and
C fibers are associated with first-order neurons that can be found in the nucleus posterior
marginalis of Rexed layer I and substantia gelatinosa of Rexed layer II. From Rexed layer I
and II, these neurons form projections that make up the three major ascending pain
pathways: the neospinothalamic, paleospinothalamic, and archispinothalamic tracts.

The neospinothalamic tract begins with nociceptive neurons located in Rexed layer I.
Second-order neurons decussate at the anterior white commissure and then ascend via the
lateral spinothalamic tract. Third-order neurons are located in the ventral posterolateral
nucleus (VPL) and the ventral posterior inferior nucleus (VPI). From the thalamus,
nociceptive information projects to the primary somatosensory cortex for further processing
and pain perception. Nociceptive information from the face and intraoral structures is
transmitted via first-order neurons in the trigeminal ganglia, which project to the pons and
spinal trigeminal nucleus in the medulla before synapsing with neurons in the ventral
posteromedial nucleus (VPM), parafascicular nucleus (PF), and the centromedian nucleus
(CM). Similar to nociceptive information from the body, the information further projects to the
primary somatosensory cortex.

The paleospinothalamic tract is the second of the three ascending pain pathways. First-order
neurons of this pathway are found in Rexed layer II, which project diffusely to Rexed layers
IV through VIII. From the spinal cord, these projections travel anteriorly and project bilaterally
onto the mesencephalic reticular formation, periaqueductal gray, tectum, PF, and the CM.
Neurons from the PF and CM send projections to the somatosensory cortex, brainstem
nuclei, and limbic areas (cingulate gyrus, insulate cortex). Emotional and visceral responses
to pain are mediated by the interplay between the limbic structures, hypothalamus, and
brainstem nuclei.

The archispinothalamic tract also mediates visceral and emotional reactions to pain. First-
order neurons are found in Rexed layer II, which project to neurons in Rexed layers IV and
VII. From the latter two layers, diffuse projections are sent to the midbrain reticular formation
and the periaqueductal gray. Neurons in the midbrain reticular formation and periaqueductal
gray then send projections to the hypothalamus, limbic system nuclei, PF, and CM nucleus.

The body is also capable of suppressing pain signals from these ascending pathways. Opioid
receptors are found at various sites at the level of the spinal cord and in structures such as
the periaqueductal gray, nucleus raphe magnus, dorsal raphe, rostral ventral medulla,
caudate nucleus, septal nucleus, hypothalamus, habenula, and hippocampus. At the level of
the spinal cord, these G-protein-coupled receptors are found on the pre-synaptic ends of
nociceptive neurons of Rexed layers IV through VII. Beta-endorphins, enkephalins, and
dynorphins serve as ligands that activate these receptors and cause cell hyperpolarization
via activating potassium channels and blocking calcium influx. The subsequent inhibition of
substance P results in blocked pain transmission. The descending pain suppression pathway
is a circuit composed of the periaqueductal gray, locus coeruleus, nucleus raphe magnus,
and nucleus reticularis gigantocellularis. The periaqueductal gray and its associated
structures are responsible for modulating the response of the body to stress, especially pain,
via opioid receptors. It suppresses information carried via C fibers, not A delta fibers, via
inhibition of local GABAergic interneurons.

The mechanisms of forming the pain :

Nociceptive pain is associated with the activation of peripheral receptive terminals of primary
afferent neurons in response to noxious chemical (inflammatory), mechanical or ischemic
stimuli.

11. The physiological sense of pain, the kinds of pain, components of

pain

Physiologically, pain occurs when sensory nerve endings called nociceptors (also
referred to as pain receptors) come into contact with a painful or noxious stimulus.
The resulting nerve impulse travels from the sensory nerve ending to the spinal cord,
where the impulse is rapidly shunted to the brain via nerve tracts in the spinal cord
and brainstem. The brain processes the pain sensation and quickly responds with a
motor response in an attempt to cease the action causing the pain.

 Types of pain:
 - Arcuate pain
Acute pain means the pain is short in duration (relatively speaking), lasting
from minutes to about three months (sometimes up to six months). Acute pain
also tends to be related to a soft-tissue injury or a temporary illness, so it
typically subsides after the injury heals or the illness subsides. Acute pain from
an injury may evolve into chronic pain if the injury doesn’t heal correctly or if
the pain signals malfunction.
  Chronic pain
Chronic pain is longer in duration. It can be constant or intermittent. For
example, headaches can be considered chronic pain when they continue over
many months or years – even if the pain isn’t always present. Chronic pain is
often due to a health condition, like arthritis, fibromyalgia, or a spine condition.

When chronic pain is classified according to pathophysiology, three types have been
described:
 Nociceptive pain: caused by stimulation of pain receptors
 Neuropathic pain: caused by damage to the peripheral or central nervous
system,s “pain arising as a direct consequence of a lesion or disease affecting
the somatosensory system” . It is usually described as a poorly localized,
electric shock-like, lancinating, shooting sensation originating from injury to a
peripheral nerve, the spinal cord, or the brain
 Psychogenic pain: caused or exacerbated by psychiatric disorders, is defined
as pain that persists despite the lack of any identified underlying physical
cause.

12. The structure-functional organization of antinociceptive (analgetic)

system
Analgesia system means the pain control system. Body has its own
analgesia system in brain, which provides a shorter relief from pain.
endogenous analgesic system. Analgesia system has got its own
pathway through which it blocks the synaptic transmission of pain
sensation in spinal cord and thus attenuates the experience of pain.
In fact analgesic drugs such as opioids act through this system and
provide a controlled pain relief.
Role of Analgesic Pathway in Inhibiting Pain Transmission
1. Fibers of analgesic pathway arise from frontal lobe of cerebral
cortex and hypothalamus
2. These fibers terminate in the gray matter surrounding the third
ventricle and aqueduct of Sylvius (periaqueductal gray matter)
3. Fibers from here descend down to brainstem and terminate on:
i. Nucleus raphe magnus, situated in reticular formation of lower
pons and upper medulla
ii. Nucleus reticularis, paragigantocellularis situated in medulla
4. Fibers from these reticular nuclei descend through lateral white
column of spinal cord and reach the synapses of the neurons in
afferent pain pathway situated in anterior gray horn Synapses of the
afferent pain pathway are between
: i. Aδ type afferent fibers and neurons of marginal nucleus
 ii. C type afferent fibers and neurons of substantia gelatinosa of
Rolando. 5.
At synaptic level, analgesic fibers release neurotransmitters and
inhibit the pain transmission before being relayed to brain.
Neurotransmitters of Analgesic Pathway
Neurotransmitters released by the fibers of analgesic pathway are
serotonin and opiate receptor substances namely enkephalin,
dynorphin and endorphin.

13. Opiate and nonopiate mechanisms of antinociceptive system

Opioids, the primary class of drugs used as

antinociceptive agents, target multiple classes of opioid
receptors in the periaqueductal gray, the spinal cord, amygdala
dostral ventral medulla, and cortex Binding to
opioid receptors disrupts information transmission in the
nociceptive circuits by decreasing conductance of voltage-
gated calcium channels and opening of inward-rectifying
potassium channels.
Activation of the opioid receptors has 2 principal effects on
nociceptive information transmission:
blocking afferent nociceptive inputs into the spinal cord;
and enhancing descending inhibition of nociceptive inputs
beginning at the level of the periaqueductal gray. These
descending projections originate in the periaqueductal
gray and project to the spinal cord through synapses in the
rostral ventral medulla. These 2 effects of opioids decrease
nociceptive information processing. In contrast, action of the
opioids in the amygdala decreases nociceptive perception and
the emotional effect of nociceptive and pain stimulation.17,18
These multisite antinociceptive effects are also one of the
mechanisms through which opioids decrease arousal.
Opioids also decrease arousal through their inhibitory
actions on brainstem cholinergic circuits at the level of the
lateral dorsal tegmental nucleus, the pedunculopontine
tegmental nucleus, the median pontine reticular formation,
and the thalamus Opioids enhance cholinergic input to
the sinoatrial node, induce bradycardia, and thereby, mitigate
sympathetic responses associated with nociception.
14. The physiological mechanisms of anesthetization

Anesthesia: is the use of drugs to prevent or reduce pain during medical procedure , the
patient is not conscious and there are not muscle movements
There are 2 major types of anesthesia:
 General anesthesia
 It makes the whole body lose feelings,movement and consciousness
 Drugs used for this type are called general anesthetics
 Anesthesia performed with general anesthetics occurs in 4 stages :
 Stage 1 : Induction
 it’s the period during which the patient goes from the state of
consciousness to a state of unconsciousness
 Stage 2 : Excitement
 At this stage the depression of inhibitory neurons in the central
nervous system leads to increased excitement involuntary muscle
movement, increased heart, rate blood pressure and respiration
 Stage 3: surgical anesthesia
 At this stage there is a gradual loss of muscle tone and reflexes.
Patient is fully unconscious, unresponsive to surgery and has regular
breathing. Best time for surgery and the anesthesiologist must pay
attention to the monitor to prevent the stage 4
 Stage 4: Medullary Paralysis or overdose
 At this stage respiratory and cardiovascular failure which leads to
death if the patient can’t be revived quickly
  Mechanism of general anesthetics (drugs)
 At a microscopic level There are 3 sites of action.
 The action of general anesthetics on thalamus and reticular activating system
leads to reversible loss of consciousness.
 The action on the hippocampus, amygdala and prefrontal cortex causes
amnesia
 The action on the spinal cord is responsible for immobility and analgesia
 At a molecular level we can divide general anesthetics into 3 groups according to
their abilities to produce unconsciousness, immobility and analgesia.
1st group : Intravenous agents
 drugs name( etomidate, propofol, barbiturates) ; there are more potent at
producing unconsciousness rather than immobility or analgesia ( used in
induction phase)
Their effectors are mediated by a subset of gamma-Aminobutyric acid type A receptors
(Gaba-A)
Gaba-A receptors are located both postsynaptically and extra synaptically on the majority of
neurons in the central nervous system. When endogenous Gaba binds to this receptors it
cause a conformational change which open central pore allowing chloride ions to pass down
electrochemical gradient
It leads to stabilization or hyperpolarization of the resting resting potential making it more
difficult for excitatory neurotransmitters to depolarize the neuron and generate an action
potential. So when the drugs bind to specific sites on the Gaba-A receptor they prolong
opening of the channel, suppress neuronal excitability and promote unconsciousness.
Side effects: Etomidate can cause adrenal suppression and transient skeletal
muscle movements including myoclonus. Propofol is known to cause respiratory
depression and hypotension. Barbiturates can cause apnea,cough, bronchospasms,
respiratory depression.

2nd group:
 Intravenous agent Ketamine and inhalation agents nitrous oxide, xenon and
Cyclopropane

NB:These drugs produce significant analgesia however their ability to produce

unconsciousness and immobility is weak , Those drugs are typically used in the maintenance
phase of anesthesia.

This group has a little or no effect on Gaba-A receptors and instead, their effects are
mediated preliminary by N-methyl-D-aspartate receptors(NMDA). NMDA receptors are
located in a spinal cord and are crucial in pain modulation and processing.
When neurotransmitter glutamate binds to NMDA receptors it causes inflow of extracellular
calcium into the postsynaptic neuron which then activates a series of signaling molecules
causing the pain signal to increase and fire more frequently.
The drugs selectively inhibit NMDA receptors which ultimately prevent or decrease
neurotransmission of pain. They also affect members of the 2-pore-domain potassium
channel which regulate the resting membrane potential of neurons.They promote
opening of these channels leading to increased potassium efflux producing reduction
in neural excitability that contributes to their sedative effects.
Side effects:
Ketamine can cause hypertension, tachycardia and hypersalivation , also dreams
hallucination(24 hours after treatment) .
 Nitrous oxide and Cyclopropane cause dizziness, nausea, vomiting
Xenon= no side effect

3rd groups: volatile anesthetic

Consist of Halothane, enflurane, isoflurane,sevoflurane and desflurane
They produce unconsciousness via different Gaba-A receptor subunits, there are also
many 2-pore domain potassium channels that are activated (high immobility).
Like Groupe 2 they inhibit NMDA receptors.
Other ion channel are sensitive to those anesthetics such as neuronal nicotinic
acetylcholine receptors , serotonin type 3 receptors, sodium mitochondrial ATP-
sensitive potassium channels and Hyperpolarization- activated cyclic nucleotide gated
channels

Side effects: it produce a dose dependent reduction in blood pressure and cardiac
output
halothane= cardiac arrhythmias and hepatotoxicity
Sevoflurane= renal toxicity

Dexmedetomidine= unique ability to produce sedation and analgesia without the risk
of respiratory depression
This effect result from its binding to the presynaptic alpha-2 adrenergic receptors of
the subtype 2A which is located in the brain and spinal cord.The action on these
receptors inhibits the release of norepinephrine, terminating the propagation of pain
signals and inducing light sedation.

Side effects: bradycardia and hypotension or hypertension due to low alpha 1

receptor agonist activity

 local or regional anesthesia

 it is used for specific target area of the body
 drugs used here are called local anesthetics

Local or regional anesthesia is used to block the conduction of action potentials in

sensory and motor nerve fibers. This usually occurs as a result of blockade
of voltage-gated Na+ channels on the nerve cell membrane. This causes a
gradual increase in the threshold for electrical excitability of the nerve, reduction
in the rate of rise of the action potential, and a slowing of axonal conduction
velocity.
There are two major categories of local anesthetics:
 ester-linked (eg, cocaine, procaine, tetracaine)
 amide linked (eg, lidocaine, bupivacaine).
In addition to either the ester or amide, all local anesthetics contain an
aromatic and an amine group. The structure of the aromatic group
determines the drug’s hydrophobic characteristics, and the amine group determines
its latency to onset of action and its potency. Application of thesedrugs into
the vicinity of a central (eg, epidural, spinal anesthesia) or peripheral nerve can
lead to rapid, temporary, and near complete interruption of neural traffic to allow a
surgical or other potentially noxious procedure to be done without eliciting pain.
Cocaine (from the coca shrub, Erythroxylan coca) was the first chemical to be
identified as having local anesthetic properties and remains the only
naturally occurring local anesthetic. Its addictive and toxic properties
prompted the development of other local anesthetics. Nociceptive fibers
(unmyelinated C fibers) are the most sensitive to the blocking effect of local
anesthetics. This is followed by sequential loss of sensitivity to
temperature, touch, and deep pressure. Motor nerve fibers are the most
resistant to the actions of local anesthetics.

General Function of Sensory Receptors Cartes | Quizlet