Pain and Pain pathway

Dr. Binu Babu Mrs. Jincy Ealias

Asso. Professor Assi. Professor
 Pain
• Pain is a complex unpleasant phenomenon
composed of sensory experiences that include
time, space, intensity, emotion, cognition, and
motivation
• Pain is an unpleasant or emotional experience
originating in real or potential damaged tissue
• Pain is an unpleasant phenomenon that is
uniquely experienced by each individual; it
cannot be adequately defined, identified, or
measured by an observer
 The experience of pain
Three hierarchial levels interact usually to produce
complex picture of pain:
1. Sensory – discriminative system (location,
intensity, quality and temporal and spatial aspects
of pain)
2. Motivational - affective system determines the
individual´s approach avoidance behaviours
(depression, anxiety)
3. Cognitive - evaluative system (thoughts
concerning the cause and significance of pain). It
may block or modulate the perception of pain.
 Pain categories
1. Nociceptive pain
a. Somatic Pain
b. Visceral Pain
2. Neuropathic Pain
3. Inflammatory Pain
4. Pain duration
a. Acute Pain
b. Chronic Pain
5. Psychogenic Pain
6. Referred Pain
7. Phantom Pain
 Pain categories
Nociceptive pain arises from a stimulation of
specific pain receptors and is a normal response to
potential damage or injury of tissues such as skin,
muscles, visceral organs, joints, tendons, or bones.
We all experience this type of pain from time to time
it tends to resolve in a reasonable amount of time.
Examples include:
• Somatic: muscles, joints, tendons, ligaments bones
or skin; this pain is often localized
• Visceral: hollow organs and smooth muscle;
usually referred
Neuropathic: Is pain initiated or caused by a problem with
the signals from the nerves. The cause can be a number of
reasons but it is often following an injury or disease of the
nervous system.
• The nature of neuropathic pain ranges from deficits
perceived as numbness to hypersensitivity (hyperalgesia
or allodynia), and to paresthesias such as tingling.
1. Allodynia-This means that the pain comes on, or gets
worse, with a touch or stimulus that would not normally
cause pain.
2. Hyperalgesia- This means that you get severe pain from a
stimulus or touch that would normally cause only slight
discomfort.
3. Paraesthesia. This means that you get
unpleasant or painful feelings even when
there is nothing touching you, and no
stimulus. For example, you may have painful
pins and needles, or electric shock-like
sensations.
Causes include, but are not limited to: diabetic
neuropathy, postherpetic neuralgia, spinal cord
injury pain, phantom limb (post-amputation)
pain, post-stroke, nerve disorders, HIV and
Alcoholism.
• Inflammatory: The body responds to
damage, injury or an underlying cause by
activating pain pathways to produce
inflammation. Although long term
inflammation can do a lot of damage,
initially, its role is protective.
• Examples include: appendicitis, rheumatoid
arthritis, inflammatory bowel disease, and
herpes zoster.
• Pain duration
– Acute pain: pain of less than 3 to 6 months
duration
– Chronic pain: pain lasting for more than 3-6
months, or persisting beyond the course of an
acute disease, or after tissue healing is
complete.
– Acute with chronic pain: It is known for
people who have a chronic pain condition to
experience acute flare-ups, also known as
setbacks.
 Psychogenic pain
• Psychogenic pain, also called
psychalgia or somatoform pain, is pain
caused, increased, or prolonged by mental,
emotional, or behavioural factors.
 Referred pain
• Referred pain is pain perceived at a location
other than the site of the painful stimulus/
origin. It's the result of a network of
interconnecting sensory nerves.
 Phantom Pain
• Phantom pain refers to the pain felt in the
area where a limb has been amputated
• Phantom pain is considered to occur
because the nerve endings at the site of the
amputation continue to send signals to the
brain that make the brain interpret the limb
is still there and the pain impulses are
coming from the amputated limb
 Neuroanatomy of pain
• The portions of the nervous system
responsible for the sensation and
perception of pain may be divided into three
areas:
• Afferent pathways
• CNS
• Efferent pathways
 Nociceptive fibers
• A-delta fibers (Að) are slow, thin,
myelinated fibers associated with
sharp/pricking, well localized
pain.
• C fibers are very slow, thin,
unmyelinated fibers that are
associated with a dull, aching,
throbbing, diffuse pain.
• A-beta (Aß), is a fast, large
diameter, myelinated fiber that
carries APs from
mechanoreceptors.
– Aß fibers are believed to modulate
C and Að activity within the dorsal
horn.
 The role of afferent and efferent pathways in
processing of pain information
Nociceptive pain
• Nociceptors: Endings of small unmyelinated and lightly
myelinated afferent neurons
• Stimulators: chemical, mechanical and thermal
• Mild stimulation  positive, pleasurable sensation (e.g.
tickling)
• Strong stimulation  pain
• Location: In muscles, tendons, epidermis, subcutanous
tissue, joints, visceral organs they are not evenly
distributed in the body (in skin more then in internal
structures)
 Afferent pathways
• From nociceptors  transmitted by small A-delta fibers
and C- fibers to the spinal cord  form synapses with
neurons in the dorsal horn (DH)
• From dorsal horn  transmitted to higher parts of the
spinal cord and to the rest of the CNS by spinothalamic
tracts
– The small unmyelinated C- neurons are responsible for
the transmission of diffuse burning or aching
sensations.
– Transmission through the larger, myelinated A- delta
fibers occurs much more quickly. A delta - fibers carry
well-localized, sharp pain sensations
 CNS
The thalamus, sensitive cortex :
• Perceiving
• Describing of pain
• Localizing
Parts of thalamus, brainstem and reticular formation: identify
dull longer lasting, and diffuse pain.
The reticular formation and limbic system: control the
emotional and affective response to pain because the cortex,
thalamus and brainstem are interconnected with the
hypothalamus and autonomic nervous system, perception of
pain is associated with an autonomic response
 Efferent Pathway
• Role: - Inhibition of afferent pain signals
• Mechanisms:
– Pain afferents on their way up to CNS send branches to
periaqueductal grey (PAG) - grey matter surrounding the
cerebral aqueduct in the midbrain, and stimulates the
neurons there  activation of efferent (descendent) anti-
nociceptive pathways.
– from there the impulses are transmitted through the spinal
cord to the dorsal horn
– there thay inhibit or block transmission of nociceptive
signals at the level of dorsal horn
 Pain pathway
The stages of pain pathway
• Transduction
• Conduction
• Transmission
• Modulation
• Perception
 TRANSDUCTION
• Transduction begins when peripheral
terminals of nociceptive (sensory receptors of
pain)
– C fibers
– A-delta
– (Aδ) fibers
• Nociceptive fibers are depolarized by noxious
mechanical, thermal, or chemical energy. The
membranes of these terminals contain
proteins and voltage-gated ion channels that
convert thermal, mechanical, or chemical
energy into an action potential (AP).
• Nociceptor terminals are spread densely
throughout the skin. They are found less on
periosteum, joints, tendons, muscles, and least
on the surface of organs.
 CONDUCTION
• Conduction of an Action
Potential is the second phase of
nociception.
• An AP generated in nociceptor
terminals is conducted across
the peripheral process to the
central process were it
depolarizes the presynaptic
terminal. The presynaptic
terminal interfaces with a
network of interneurons and
second order neurons in the
dorsal horn. Interneurons can
facilitate or inhibit transmission
to second order neurons
• These nociceptors projects from the
trigeminal ganglion and enter the CNS at the
level of the pons. Trigeminal Að and C fibers
pass down through the pons into the
medulla where they synapse on second
order neurons which then rise to decussate
within the pons and pass to the thalamus.
 MODULATION
• Modulation of
nociceptive transmission
is an adaptive process
involving both excitory
and inhibitory
mechanisms. The
responses of second
order neurons can be
suppressed or facilitated
dependent on
importance of the event.
 PERCEPTION
• Perception of nociceptive pain is dependant upon neural
processing in the spinal cord and several brain regions.
Pain becomes more than a pattern of nociceptive action
potentials when they reach the brain.
• Action potentials ascending the spinothalamic tract are
decoded by the thalamus, sensorimotor cortex, insular
cortex and the anterior cingulate to be perceived as an
unpleasant sensation that can be localized to a specific
region of the body.
• Action potentials ascending the spinobulbar tract are
decoded by the amygdala and hypothalamus to generate
a sense of urgency and intensity. It is the intergration of
sensations, emotions and cognition that result in our
perception of pain.
 REFLEX ARC
• The pathway followed by nerve impulses
that produce a reflex is the reflex arc.
• Reflexes occur over highly specific neural
paths (reflex arcs), all of which have five
essential components
a. Receptor: This is the site of the stimulus
action. The receptor is the part of the neuron
(usually a dendrite) that detects a stimulus.
Receptor responds to a stimulus.
b. Sensory neuron: Afferent sensory neuror
transmits impulses to the CNS.
• Integration centre: The integration centre is
always within the CNS. The integration centre
involves one synapse or multiple synapses.
– Monosynaptic reflex (1 synapse, rapid): In simple
reflex arcs, there may be a single synapse between a
sensory neuron and a motor neuron (monosynaptic
reflex)
– Polysynaptic reflex: More complex (but slow) reflex
arcs involve multiple synapses with chains of
interneurons. Here, one or more interneurons
constitute the integration centre.
• Motor neuron: Efferent motor neuron conducts
impulses from the integration centre to an
effector organ.
• Effector: Effector is a muscle or gland that
receives the impulse from the motor neuron
and responds to the efferent impulses (by
contracting or secreting).
– In somatic reflexes, the effector is skeletal muscle.
– In autonomic (visceral) reflexes, the effector is
smooth or cardiac muscle or a gland.
 References
• Acree, T. E., & Beidler, L. M.
(1971). Taste,. Berlin, New York, Springer-
Verlag.
• Per Brodal. (2010). The central nervous
system : structure and function. Oxford
University Press, Cop.
• Nieuwenhuys, R., J Voogd, Voogd, J., &
Christiaan Van Huijzen. (2008). The Human
Central Nervous System. Springer.