Physiology of Pain

By
Dr. Marwa Mostafa
 Pain definition

* Pain is a physiologic consequence of tissue injury and serves a

vital protective function.
* The International Association for the Study of Pain defines
pain as “an unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or described in
terms of such damage.
* Pain is a signal in your nervous system that say something
may be wrong.
N.B

Clinicians often treat patients with pain with the goal of reducing or
eliminating pain, it is important to note that pain is an important
protective sensation. In this manner, pain can serve as an indicator of
pathology, physical stress, or injury. Therefore, when pain is present,
treatment should be targeted to solve the underlying cause.
 The purpose or function of pain
 Protective function:

A withdrawal reflex response to an acute noxious stimulus is an understandable and

necessary reaction that has an obvious protective function even in the absence of conscious
perception.
 Biological function:

More importantly, the experience of pain may lead to the avoidance of potentially harmful
situations and possible injury. Immobility and withdrawal due to pain may serve to
provide an environment in which healing and restoration of function can occur.
 Classification of pain:

1) According to inferred pathophysiology

 Two Basic (main) Categories of Pain:

Nociceptive pain Neuropathic

pain
Somatic visceral Central Peripheral
nervous nervous
system system
Superficial deep Arising Arising from parietal
from peritoneum or pleura
Viscera
itself
 Nociceptive pain:

Typical type of pain:

 Everybody has experienced this (tooth ache, fracture, skin lesion).
Subtypes of Nociceptive Pain
Somatic Pain: (Associated with skin and musculo-skeletal region).

• Superficial (skin layers).

• Deep (internal structures).
Visceral Pain ( Associated with viscera and internal organs)

• Arising from viscera itself

 Neuropathic Pain

Neuropathic pain can be defined as pain initiated or caused by a primary lesion or

dysfunction in the nervous system.

Abnormal processing of the impulses either by the peripheral or central nervous system.
 2) According to duration of pain
A) A cute: Acute pain is a symptom that results from injury and/ or disease that causes or can cause tissue damage
through infection, trauma, the progression of a metabolic disorder, or a degenerative disease.
Acute pain:
• Lasts less than 12 weeks, subsides once the healing process is accomplished
• Sharp, easy to locate (skin), but diffuse, difficult to locate( muscles, joints or viscera).
• Fast, pricking.
• Occurs very rapidly.

• Carried by large diameter myelinated Aδ fibers.

• Usually alleviated with the help of professional.

• Acute pain serves to protect against further tissue damage, and when tissue injury is present, pain may be
maintained to allow time for proper tissue healing.
• Therefore, the symptoms can reflect the underlying pathology.
The stimulus responsible for acute pain is associated with increased muscle tone,
heart rate, blood pressure, skin impedance, and other manifestations related to the
increase of activity of the sympathetic nervous system. Autonomic, psychological,
and behavior responses persist while the stimulus is present.
B)Sub-acute:
* Intermediate stage between acute and chronic stages
* Begins after the acute stage pass by and lasts for few weeks.
C) Chronic: Chronic pain is commonly defined as persistent or recurrent pain existing for more than 3 to 6 months
or pain that persists beyond the normal time expected for healing of injured tissue.
* Involves complex processes and pathology. Usually involves altered anatomy and neural pathways.
* Burning, aching.
* Gradually increases.
* Carried by small diameter non-myelinated ‘C’fibers.
* Pain often increases over time & is aggravated by many factors.
* Chronic pain follows acute pain and is also associated with structural and functional changes in the central nervous
system that require multiple therapeutic approaches
Characteristics a n d functions of C fibre a n d A-delta fibres
C fibres A-delta fibres
Characteristics: Characteristics:
 Primary afferent fibres  Primary afferent fibres
 Small diameter  Large diameter
 Unmyelinated  Myelinated
 Slow conducting  Fast conducting
Receptor type: Receptor type:
 Polymodal respond to more than one type of  High-threshold mechanoreceptors respond
noxious stimuli: mechanical stimuli over certain intensity.
 Mechanical
 Thermal
 Chemical
Pain quality: Pain quality:
 Well-localized
 Diffuse
 Sharp
 Dull
 Stinging
 Burning
 Pricking
 Aching
 Referred to as ‘fast’ or ‘first’ pain
 Referred to as ‘slow’ or second’ pain
 3)According to onset

A)Sudden: as in cases of trauma, accidents, stabbing or pricking pain.

B)Gradual: take prolonged period and gradually increases all over time as in cases of
cancer, and osteoarthritis.
 4)According to perception of pain distribution

A) Localized pain (commonly during acute stage).

B)Referring pain (commonly occur due to malfunctioning / disturbance of some functions

of an organ causing pain to be referred to other organs, as in colon distension and in
colic pain they may refer pain to back region).

C)Radiating pain (commonly due to neurological problem, as bracialgia and sciatica).

 Referred Pain
 Referred pain is defined as pain that occurs at a site remote from the

source of the disease or injury, usually a visceral or muscle source

 Occur due to convergence of cutaneous, visceral, and skeletal

muscle nociceptors on the common nerve root of the spinal cord.

 The brain interprets the afferent input as arising from cutaneous

structures because of the higher proportion of cutaneous afferents

converging on second-order transmission neurons.

 A common example is referred pain that radiates to the left

shoulder, arm, jaw, or chest during angina or myocardial

infarction
 Pain Receptors (Nociceptors)

• Specialized receptors called nociceptors signal actual or potential tissue damage.

• The receptors in the skin are understood better than the receptors found in the viscera

and cardiac and skeletal muscle.

• The nociceptors are three distinct types of free nerve endings that respond to different

stimulus modalities
 The nociceptors do not normally respond to sensory stimuli in nondamaging ranges.

 For example, high-threshold mechanoreceptors (HTMs) do not usually respond to light

touch. The sensitivity of HTMs increases following mild injury, however, causing the
surrounding tissue to become more sensitive to pressure.

 Polymodal nociceptors become increasingly sensitive following repeated heat or

chemical activation, possibly accounting for the hyperalgesia experienced in injured

skin.
Nociceptors are further classified into four types:

 The first type is termed high threshold mechanonociceptors or specific nociceptors.

 These nociceptors respond only to intense mechanical stimulation such as pinching,

cutting or stretching.

 The second type is the thermal nociceptors, which respond to the intense heat and cold.

 The third type is chemical nociceptors, which respond only to chemical substances.

 A fourth type is known as polymodal nociceptors, which respond to high intensity

stimuli such as mechanical, thermal and to chemical substances like the previous three
types.
 Nociception

 The physiologic component of pain is termed nociception, which consists of the

following processes:

 Transduction

 Transmission

 Perception

 Modulation of neural signals generated in response to an external noxious stimulus.

 Transduction of pain
• Transduction is the process by which afferent nerve endings participate in translating
noxious stimuli (e.g., a pinprick) into nociceptive impulses

• Transduction begins when the free nerve endings (nociceptors) of C fibres and A-delta
fibres of primary afferent neurones respond to noxious stimuli.

• Nociceptors are exposed to noxious stimuli when tissue damage and inflammation
occurs as a result of, for example, trauma, surgery, inflammation, infection, and
ischemia.
The nociceptors are distributed in the;

 Somatic structures (skin, muscles, connective tissue, bones, joints);

 Visceral structures (visceral organs such as liver, gastro-intestinal tract).

Transduction of pain
 Transduction of pain
Chemical mediators such as
 Prostaglandin;

 Bradykinin;

 Serotonin;

 Substance P;

 Potassium;

 Histamine.

Chemical mediators are released to the vicinity of nociceptors that may be activated and sensitized.
The resultant "soup" of chemical mediators also changes the transduction sensitivity of
nociceptors, resulting in reduction of threshold for activation and increased response to
suprathreshold stimulus, i.e., peripheral sensitization.
 Transmission of pain (Pain Pathway)
The transmission process occurs in three stages.
1- The pain impulse is transmitted from the site of transduction along the nociceptor
fibers to the dorsal horn in the spinal cord;(first order neuron)
Pain impulses are transmitted by two fiber systems:
Aδ fibers are myelinated, 2 – 5 μm in diameter and conduct at rates of 12 – 30 m/s,
C fibers are unmyelinated, 0.4–1.2μm in diameter and conduct at rates of 0.5 to 2 m/s.
2- From the spinal cord to the brain stem and thalamus. The
fibers cross to the opposite side of the spinal cord, and then
ascend to brain stem and thalamus (second order neuron)
via the anterolateral system which actually contains at least
two main pathways:

 The first is called the spinothalamic pathway.

The most direct route to the thalamus, it is also known as the

neospinothalamic or direct pathway for fast pain.

 The second is known as the spinoreticular pathway-

also called the paleospinothalamic or indirect path for

slow pain
 The presence of two pain pathways explains the existence of two components of pain:
 fast, sharp and well localized sensation (first pain) which is conducted by Aδ
fibers; and
 a duller slower onset and often poorly localized sensation (second pain) which is
conducted by C fibers.
 The spinomesencephalic tract ascends to the midbrain and terminates in periaqueductal
gray (PAG).
 Spinomesencephalic cells terminating in the PAG may activate a descending inhibitory
system that promotes analgesia due to the release of serotonin.
 The spinothalamic tract transmits signals that are important for pain localization.
 The spinoreticular tract is constituted by cells that ascend to the medullary reticular
formation and to the pontine reticular formation.
 This pathway is involved in the emotional aspects of pain.
3-from the thalamus to the somatosensory areas of the
cerebral cortex. (third order neuron )
 Perception of pain

• Perception of pain is the end result of the neuronal activity of pain transmission and
where pain becomes a conscious multidimensional experience.

• The multidimensional experience of pain has affective-motivational, sensory-

discriminative, emotional and behavioural components.

• When the painful stimuli are transmitted to the brain stem and thalamus, multiple
cortical areas are activated and responses are elicited.
 These areas are:

 The reticular system: This is responsible for the autonomic and motor response to pain and for
warning the individual to do something, for example, automatically removing a hand when it
touches a hot saucepan.
 It also has a role in the affective- motivational response to pain such as looking at and assessing
the injury to the hand once it has been removed form the hot saucepan.
 Somatosensory cortex: This is involved with the perception and interpretation of sensations.
 It identifies the intensity, type and location of the pain sensation and relates the sensation to past
experiences, memory and cognitive activities.
 It identifies the nature of the stimulus before it triggers a response, for example, where the pain
is, how strong it is and what it feels like.
 Limbic system: This is responsible for the emotional and behavioural responses to pain for
example, attention, mood, and motivation, and with processing pain and past experiences of pain.
 Modulation of pain

The modulation of pain involves changing or inhibiting transmission of pain impulses in the
spinal cord. The multiple, complex pathways involved in the

I- Spinal modulation (at spinal cord level)

The gate control theory of pain
 It is the most used theory to explain the inhibition of pain by therapeutic modalities.

 This theory proposes that stimulation of large-diameter afferent nerve fibers (Aβ)

(transmit mechanical and thermal sensation) activates local inhibitory circuits in the
dorsal horn of the spinal cord and prevents nociceptive impulses carried by small-
diameter nerve fibers (C and Aδ) from reaching higher brain centers.
 The gray matter of the spinal cord is divided into 10 layers

(Rexed laminae), which basically progress from posterior to

anterior (as laminae I–X).
 The incoming pain fibers (Aδ and C) synapse in laminae I–V

( lamina V called T cell), whereas Aβ fibers from cutaneous

mechano- & thermo- receptors synapse in laminae III–VI.
 Laminae II and III (the substantia gelatinosa, SG) consists of

small, densely packed interneurons that act as a gate for

transmission of pain stimuli.
 These interneurons have an inhibitory effect on the terminals

of pain fibers that synapse with the T cell

 According to the original gate control theory of pain, when Aβ

fibers are activated, they send excitatory stimuli through a

collateral branch that activates the substantia gelatinosa (SG)
interneurons that inhibit the pain fiber terminals and T cell
activity.
 Therefore, SG interneurons close the gate to nociceptive

traffic and reduce pain.

 On the other hand, Aδ and C fibers send an inhibitory

collateral branch that reduces the inhibitory effect of SG upon

the pain fiber terminals, increasing the firing of the T cell.
 In this case, the gate is open and nociceptive traffic can

proceed to upper centers, resulting in pain

2-Supraspinal modulation (Descending modulation)
• The endogenous opiate theory of pain
• It is that the inhibitory effects from the higher center come
principally from periaqueductal grey matter (PAG)which is located
at midbrain ,and raphe nucleus (RN) (located in the medulla).

• These both have excitatory effects on the inhibitory interneurons

of the substantia gelatinosa, and so can reduce the pain
transmission.

• These descending pathway are thought to exert their effect

through releasing of serotonin which in turn will activate the
encephalin interneuron located at substantia gelatinosa