The document discusses pain transduction, transmission, and modulation. It begins by describing sensory receptors including nociceptors, which detect potentially harmful stimuli and transduce them into neural signals. Nociceptive fibers called Aδ and C fibers transmit these signals to the spinal cord. Transduction involves converting stimuli into neural signals, transmission moves these signals through the nervous system, and modulation regulates signal strength. The spinothalamic tract then relays nociceptive information from the spinal cord to the thalamus and cortex, allowing the perception of pain.

1. Pain Transduction & Transmission
Aditya Johan Romadhon, SST.Ft, M.Fis

2. Sensory receptors
Photoreceptors are those in the rods and cones in the retina that respond to light
The term chemoreceptor refers to receptors stimulated by a change in the chemical composition of the environment in which they are located (taste and smell as well as visceral
receptors such as those sensitive to changes in the plasma level of O2, pH)
Potentially harmful stimuli such as pain, extreme heat, and extreme cold are mediated by nociceptors
Thermoreceptors detect the sensations of warmth and cold
Proprioceptors are located in muscles, tendons, and joints and relay information about muscle length and tension
The cutaneous receptors for touch and pressure are mechanoreceptors
Sensory receptors can be thought of as transducers that convert various forms of energy in the environment into action potentials in sensory neurons

3. Cutaneous Mechanoreceptors
Touch and pressure are sensed by
four types of mechanoreceptors
Meissner’s corpuscles are dendrites
encapsulated in connective tissue and
respond to changes in texture and
slow vibrations
Merkel cells are expanded dendritic
endings, and they respond to
sustained pressure and touch
Ruffini corpuscles are enlarged
dendritic endings with elongated
capsules, and they respond to
sustained pressure
Pacinian corpuscles consist of
unmyelinated dendritic endings of a
sensory nerve fiber, 2 μm in diameter,
encapsulated by concentric lamellae
of connective tissue that give the
organ the appearance of a cocktail
onion, respond to deep pressure and
fast vibration
The sensory nerves from these
mechanoreceptors are large
myelinated Aα and Aβ fibers whose
conduction velocities range from −70–
120 to −40–75 m/s,

4. Pain receptor (nociceptor)
Nociceptors can
be separated into
several types
Mechanical
nociceptors
respond to strong
pressure (eg, from
a sharp object)
Thermal
nociceptors are
activated by skin
temperatures
above 42°C or by
severe cold
Chemically
sensitive
nociceptors
respond to various
chemicals like
bradykinin,
histamine, high
acidity, and
environmental
irritants
Polymodal
nociceptors
respond to
combinations of
these stimuli.

5. Pain receptor (nociceptor)
There are a variety of receptors located on the endings of nociceptive sensory nerves that respond to noxious thermal,
mechanical, or chemical stimuli
Many of these are part of a family of nonselective cation channels called transient receptor potential (TRP) channels.
This includes TRPV1 receptors (the V refers to a group of chemicals called vanilloids) that are activated by intense heat,
acids, and chemicals such as capsaicin (the active principle of hot peppers and an example of a vanilloid)
TRPV1 receptors can also be activated indirectly by initial activation of TRPV3 receptors in keratinocytes in the skin
Noxious mechanical, cold, and chemical stimuli may activate TRPA1 receptors (A, for ankyrin) on sensory nerve terminals
Sensory nerve endings also have acid sensing ion channel (ASIC) receptors that are activated by pH changes within a
physiological range and may be the dominant receptors mediating acid-induced pain
In addition to direct activation of receptors on nerve endings, some nociceptive stimuli release intermediate molecules that
then activate receptors on the nerve ending
For example, nociceptive mechanical stimuli cause the release of ATP that acts on purinergic receptors (eg, P2X, an
ionotropic receptor and P2Y, a G protein-coupled receptor)
Tyrosine receptor kinase A (TrkA) is activated by nerve growth factor (NGF) that is released as a result of tissue damage.

6. Nociceptors

7. Nociceptive nerve fiber
Impulses from
nociceptors are
transmitted via two fiber
types, thinly myelinated
Aδ fibers (2–5 μm in
diameter) that conduct at
rates of −12–35 m/s and
unmyelinated C fibers
(0.4–1.2 μm in diameter)
that conduct at low rates
of −0.5–2 m/s
Activation of Aδ fibers,
which release glutamate,
is responsible for fast
pain which is a rapid
response and mediates
the discriminative aspect
of pain or the ability to
localize the site and
intensity of the noxious
stimulus
Activation of C fibers,
which release a
combination of glutamate
and substance P, is
responsible for the
delayed second pain also
called slow pain which is
the dull, intense, diffuse,
and unpleasant feeling
associated with a noxious
stimulus

8. Itch and tickle are also related to pain
sensation
itch-specific fibers have been
demonstrated in the ventrolateral
spinothalamic tract
Itching can be produced not only by
repeated local mechanical stimulation
of the skin but also by a variety of
chemical agents including histamine
and kinins such as bradykinin which
are released in the skin in response to
tissue damage

9. The pain
Pain is defined as an unpleasant sensory and emotional experience
associated with actual or potential tissue damage
As shown by the definition, pain serves the purpose to prevent
tissue damage and protect the body while it is healing
Under certain conditions, pain can become maladaptive and
persist as chronic pain
This pain serves no protective function and is described as
pathological pain as opposed to physiological pain

10. transduction, transmission and modulation when there is a presence of noxious stimuli.
Fundamentally, the basic pain mechanism undergoes three events
Both nociceptors remain silent during homeostasis in the absence of pain and are activated when there
is a potential of noxious stimulus
The sensation of pain is associated with the activation of the receptors in the primary afferent fibers,
which is inclusive of the unmyelinated C-fiber and myelinated A delta fiber

11. Transduction
Transduction refers to the process by
which a painful physical or chemical
stimulus is transformed into a signal
that can be carried (via transmission)
to the central nervous system and
perceived as pain

12. Transduction
Transduction occurs along
the nociceptive pathway
following such order:
Stimulus events are
converted to chemical
tissue events
Chemical tissue and
synaptic cleft events are
then changed into electrical
events in the neurons
Electrical events
in the neurons
are transduced
as chemical
events at the
synapses

13. Transmission & Modulation
After the completion of
transduction, the following
mechanism would be
transmission. It takes place by
transmitting the electrical events
along the neuronal pathways
Meanwhile, the modulation
event takes place at all level of
nociceptive pathways through
the primary afferent neuron, DH
and higher brain center by up-
or down-regulation.

14. Route of pain transmission
Within the ascending system, primary afferent nociceptors are responsible for conveying the noxious
information received to the projection neurons in the DH of the spinal cord
Following that, a subset of these projection neurons in turn transmit these sensory information up
to the thalamus reaching the somatosensory cortex through the spinothalamic tract, thus
providing information on the intensity and the location of the noxious stimulus.
The spinothalamic tract is located in the whitematter of spinal cord and consists of two parts
The lateral spinothalamic and anterior spinothalamic tracts, which have different courses of
function
The lateral spinothalamic tract focuses on transmission of the pain and temperature sensation,
while the anterior spinothalamic tract carries information related to the crude touch and firm
pressure sensation towards the thalamus in the brain.

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