The document discusses pain pathways and mechanisms of pain control. It defines pain and describes different types of pain such as acute vs chronic, nociceptive vs neuropathic, somatic vs visceral, referred vs non-referred, and somatogenic vs psychogenic pain. It then explains the neuroanatomy of pain transmission from nociceptors to the central nervous system and perception in the brain. Finally, it discusses current analgesic options and the WHO analgesic ladder for treating mild to severe pain.

1. Pain Pathway, Transmission, and
Control
By
(
Hesham Marei
BDs, MSc, PhD, FDS RCS (Eng
Assistant Professor
,Oral and Maxillofacial Surgery

2. Objectives
•
•
•
•
Definition of Pain
Types of Pain
Pain Pathway
Mechanism of Pain Control

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

4. Types of pain
•
•
•
•
•
Acute versus chronic
Nociceptive versus Neuropathic
Somatic versus visceral
Referred versus non referred pain
Somatogenic versus psychogenic

5. Acute vs chronic

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

7. Nociceptive v Neuropathic
• 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…)

8. Somatic v Visceral
• 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.

9. Referred pain
• 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)

10. Somatogenic versus psychogenic
• 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.

11. 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.

12. 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

13. The role of the afferent and efferent pathways in
processing of pain information
Nociceptors: Endings of small unmyelinated and lightly
myelinated afferent neurons.
Stimulators:
Location:
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.
In muscles, tendons, epidermis, subcutanous tissue,
Visceral.
- they are not evenly distributed in the body
(in skin more then in internal structures)

14. Nociceptive pain:
- mechanisms involved
in development

15. Types of stimuli
• Receptors respond to injury
– Thermal –excessive heat or cold
– Mechanical –tearing, crushing, stretching etc
– Chemical
• Inflammatory mediators
• Lactic acid
• ischemia

16. Pain pathway
There are four processes in
the pain pathway
1. transduction
–
2.
Noxious stimuli translated into electrical activity at sensory
nerve endings
Transmission
–
3.
Propagation of impulses along spinothalamic pathway.
Modulation
–
4.
Transmission is modified
Perception
–
Affective / motivational aspect
Each of these processes present a potential target for
analgesic therapy

17. Transduction - receptors
• 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.

18. Transduction -Receptor
activation
• 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

19. Transduction
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


20. Transduction
A delta fibres and C fibres
• 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 depolarisation occurs along these
fibres in the form of action potentials

21. Transduction - A delta fibres and C fibres
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

22. Primary (1o) Afferents
sharp’‘
localized
Aδ
dull’‘
vague
C

24. Pain Transmission Pathway
• 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
gene-related peptide (CGRP).

25. Pain Transmission Pathway
• 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. Normal Pain Pathways
cortex
thalamus
Tissue injury
• histamine
• bradykinin
• etc.
dorsal root
ganglion
primary
afferent
lateral spinothalamic tract
Fig 3-25

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

28. • • nociceptors →
transmitted by small Adelta fibers and Cfibers 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. Mechanisms of Pain
Central Sensitization

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

37. Sites of Action
NSAIDs
Aa
COX
PGs

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

39. Sites of Action
Opioids
(µ, δ, κ)

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

41. ’WHO Analgesic ‘Ladder
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)