This document provides an overview of pain, including its definition, types, and pathway in the human body. It discusses how pain is sensed by nociceptors and transmitted through the nervous system to be perceived in the brain. Acute and chronic pain are compared, and the mechanisms of nociceptive and neuropathic pain explained. Somatic, visceral, referred, somatogenic, and psychogenic pain are defined. The neuroanatomy and physiology of pain processing through transduction, transmission, modulation, and perception are outlined in detail.

1. By
Hesham Marei
BDs, MSc, PhD, FDS RCS (Eng)
Assistant Professor
Oral and Maxillofacial Surgery,

2. Definition of Pain
Types of Pain
Pain Pathway
Mechanism of Pain Control

3. An unpleasant sensory and emotional experience
associated with actual or potential tissue damage.

4. 




Acute versus chronic
Nociceptive versus Neuropathic
Somatic versus visceral
Referred versus non referred pain
Somatogenic versus psychogenic

5. Acute pain
Chronic pain
•Sudden onset
•Temporary (disappears once
stimulus is removed)
•Persistent – usually lasting
more than six months
•can be somatic, visceral,
referred
•Cause unknown – may be due
to neural stimulation
•Physiological responses to
acute pain include increased
RR, HR, BP and reduction in
gastric motility – sympathetic
response)
•Physiological responses are
less obvious especially with
adaptation.
•Psychological responses may
include depression

6. Nociceptive pains result from activation of
nociceptors (Pain receptors)
Neuropathic pain result from direct injury to nerves
in the peripheral nervous system. (Alcoholism,
diabetic neuropathy, post-herpetic neuralgia, etc…)

7. Somatic pain
 Superficial: stimulation of receptors in skin
 Deep: stimulation of receptors in muscles, joints and
tendons
Visceral pain
 Stimulation of receptors in internal organs, abdomen
and skeleton
 Often poorly localised as fewer receptors located in
viscera
 Visceral pain can be referred.

8. Pain experienced at a point distant to its point of
origin
Area of referred pain is supplied by same spinal
segment as actual site of pain
Brain misinterprets signals as coming from somatic
regions
Knowledge of different types of referred pain is
important in clinical diagnosis because in many
visceral ailments the only clinical signs is referred
pain.
Good section on referred pain can be found in
Guyton and Hall (2006)

9. Somatogenic pain is a pain originating from an actual
physical cause e.g. trauma, ischaemia etc
Psychogenic pain is pain for which there is no
physical cause. It is not however imaginary pain and
can be as intense as somatic pain.

10. Pain threshold
The pain threshold is the point at which a stimulus is perceived as pain.
A patient who is hyper-reactive is considered to have a low pain threshold. On the
other hand a patient with a high pain threshold can tolerate pain.
The pain threshold is affected by:
•Emotional status.
•Fatigue.
•Age.
•Sex.
•Fear and Apprehension.

11. Neuroanatomy of pain
The portions of the nervous system responsible for the
sensation and perception of pain may be divided into three
areas:
1. afferent pathways
2. CNS
3. efferent pathways
The afferent portion is composed of:
a) nociceptors (pain receptors)
b) afferent nerve fibres
c) spinal cord network

12. The role of the afferent and efferent pathways in
processing of pain information
Nociceptors: Endings of small unmyelinated and lightly
myelinated afferent neurons.
Stimulators:
Chemical, mechanical and thermal stimuli
Mild stimulation → positive, pleasurable sensation
(e.g. tickling)
Strong stimulation → pain
These differences are a result of the frequency
and amplitude of the afferent signal transmitted
from the nerve endings to the CNS.
Location:
In muscles, tendons, epidermis, subcutanous tissue,
Visceral.
- they are not evenly distributed in the body
(in skin more then in internal structures)

13. Nociceptive pain:
- mechanisms involved
in development

14. Receptors respond to injury
 Thermal –excessive heat or cold
 Mechanical –tearing, crushing, stretching etc
 Chemical
Inflammatory mediators
Lactic acid
ischemia

15. There are four processes in
the pain pathway
1.
transduction

1.
Transmission

1.
Propagation of impulses along spinothalamic pathway.
Modulation

1.
Noxious stimuli translated into electrical activity at sensory nerve
endings
Transmission is modified
Perception

Affective / motivational aspect
Each of these processes present a potential target for analgesic
therapy

16. Pain is detected by nociceptors (noci = harmful)
Free nerve endings of sensory neurones Found in all
tissues and organs (except brain)
Can be classified as either:
 Unimodal – respond to only one type of stimulus
 Polymodal – respond to more than one type of stimuli.

17. When cellular damage occurs, tissues release
chemicals that stimulate nociceptors
 Bradykinin
Histamine
 Serotonin
Acetylcholine
 Potassium ions
 Prostaglandins (PGE2, PGI2)
 Substance P
The activity and sensitivity of nociceptors is
profoundly altered by such mediators (enhances
receptor response to noxious stimuli).
See article by Kelly et al ( 2001) for interesting
information on this aspect

18. TRAUMA
•Mechanical
•Thermal
•chemical
Overall effect is increased
nociceptor activation
r
epto
c
noci
Mediators
Bradykinin Histamine
Serotonin Acetylcholine
Potassium ions
 Prostaglandins (PGE2, PGI2)
Substance P


19. Nociceptors respond to noxious stimuli and
covert energy at the site of the stimulus into
neural impulses
Nociceptors are terminal endings of primary
afferent fibres. These can be classed into two main
types
 Myelinated A-delta fibres
 non-Myelinated C fibres
When the threshold level of the stimulus is
reached, then depolarization occurs along these
fibres in the form of action potentials

20. A-Delta fibres
C- fibres
Myelinated
Unmyelinated
fast ( first) pain -conduct at 535m/sec
Slow (second) pain – conduct at
0.5-2.0m/sec
Associated with Sharp, brief,
prinking pain
Associated with dull,burning,
aching, prolonged pain
Well localised
More diffuse
Elicited by mechanical or thermal
stimuli
Elicited mainly by chemical stimuli
or persisting mechanical or
thermal stimuli

21. Primary (1o) Afferents
‘dull’
vague
Aδ
C

24.  Both A delta and C nociceptor fibres synapse in the dorsal
horn of the spinal cord
 Evidence suggests that neurotransmitters released at this
point include substance P, glutamate, calcitonin generelated peptide (CGRP).

25. Secondary neurones cross the cord and ascend
through the antero-lateral spinothalamic tract to the
thalamus where they synapse with tertiary neurones
These tertiary neurones ascend from the thalamus to
somatosensory cortex.

26. cortex
thalamus
Tissue injury
• histamine
• bradykinin
• etc.
dorsal root
ganglion
primary
afferent
lateral spinothalamic tract
Fig 3-25

27. Somatosensory cortex is involved in the
localisation and identification of pain.

28.  • nociceptors →
transmitted by small Adelta fibers and C- fibers
to the spinal cord → form
synapses with neurons in
the dorsal horn(DH)
 From DH → transmitted
to higher parts of the
spinal cord and to the rest
of the CNS by
spinothalamic tracts

30. Central Sensitization

31. Transduction, transmission, modulation interact to
create subjective emotional experience of pain.
The portion of CNS involved in the interpretation
of the pain signals are the limbic system,
reticular formation, thalamus, hypothalamus and
cortex

32. The brain first perceives the sensation of pain
• The thalamus, sensitive cortex :
perceiving
describing
localising
of pain
• 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, the perception of pain is associated with an
autonomic response

33. Theory of pain production and modulation
• Most rational explanation of pain production and modulation
is based on gate control theory (created by Melzack and Wall)
• According to this theory, nociceptive impulses are
transmitted to the spinal cord through large A- delta and
small C- fibers
• These fibers create synapses in the SG
• The cells in this structure function as a gate, regulating
transmission of impulses to CNS

34. Stimulation of larger nerve fibers (A-alfa, A-beta) causes the cells in SG to "close the
gate".
A closed gate decreases stimulation of T-cells (the 2nd
afferent neuron), which decreases transmission of impulses,
and diminishes pain perception
Stimulation of small fiber input inhibits cells in SG and
"open the gate".
An open gate increases the stimulation of T-cells →
→↑ transmission of impulses → enhances pain perception
• In addition to gate control through large and small fibers
stimulation, the central nervous system, through efferent
pathways, may close, partially close, or open gate.
Cognitive functioning may thus modulate pain perception

36. Perception of pain is dependent upon:
 Cellular damage
 Receptor stimulation
 Ascending neural pathways
 Sensory cortex arousal
 Conscious awareness of stimulation of pain

37. NSAIDs
Aa
COX
PGs

38. Local
Anesthetics
(voltage-gated
Na+ channels)

39. Opioids
(µ, δ, κ)

40. NSAIDs: 1970’s
opioids: 1970’s
tramadol: 1980’s & 1990’s
COX-2 inhibitors: 1990’s
acetaminophen: unknown
combinations
adjuncts

41. Severe
Moderate
Mild
Step 3
Strong opioids (e.g., morphine)
with or without non-opioids
Step 2
Weak opioids (e.g., codeine)
with or without non-opioids
Step 1
Non-opioids (e.g., NSAIDs,
acetaminophen = paracetamol)