PAIN THEORY AND PATHWAYS Moderator: Dr. KSR MURTHY SIR Dr. VIKAS JOSHI SIR Presenter: Dr. SOUJANYA MR

PAIN THEORY AND PATHWAYS

Moderator: Dr. KSR MURTHY Dr. VIKAS JOSHI Presenter: Dr. SOUJANYA M

1. Moderator: Dr. KSR MURTHY SIR
Dr. VIKAS JOSHI SIR
Presenter: Dr. SOUJANYA MR
PPAIN THEORY AND
PATHWAYS

2. DEFINITION OF PAINDEFINITION OF PAIN
The International Association for the
Study of Pain
Pain is
"an unpleasant sensory and emotional experience
associated with actual or potential tissue
damage, or described in terms of such damage"

3. INCIDENCEINCIDENCE
Pain is one of the most common reason for visiting a
physician.
It is estimated that chronic pain may affect as many as
40% of the adult population.
The prevalence of low back pain ranges from 8% to
37% and is particularly prominent in patients between
45 to 60 years.
It is estimated that 40 million persons experience
musculoskeletal pain conditions
The most common pain is toothache, which is
estimated to have occurred in 12.3% of population.

( helmick et al.,1995)

4. HISTORYHISTORY
Derived from Latin -“Poena” meaning
punishment from God.
Homer thought pain was due to arrows shot by
God.
Aristotle, who probably was the first to distinguish
five physical senses considered pain to the
“passion of the soul” that somehow resulted from
the intensification of other sensory experience.

5. Plato contented, pain and pleasure arose from
within the body, an idea that perhaps gave birth
to the concept that pain is an emotional
experience more than a localized body
disturbance.
The Bible makes reference to pain not only in
relationship to injury and illness but also an
anguish of the soul.

6. Purpose of PainPurpose of Pain
 It causes the host organism to stop or fix
whatever is causing the discomfort
 It also reduces the likelihood of further
injury
 Acute pain is protective, but when it
becomes chronic, it no longer serves a
purpose.
 Pain promotes the healing process as we
take great care to protect an injured body
part form further damage as to minimize
the experience of more pain.

7. The experience of painThe experience of pain
Three systems interact usually to produce pain:
1. Sensory - discriminative
2. Motivational - affective
3. Cognitive – evaluative
1. Sensory - processes information about the strength, intensity,
quality and temporal and spatial aspects of pain
2. Motivational - determines the individual´s approach
3. Cognitive - overlies the individuals learned behaviour
concerning the experience of pain. It may block, modulate, or
enhance the perception of pain

8. CLASSIFICATION OF PAINCLASSIFICATION OF PAIN
Pain can be classified into :
Acute pain : which is caused by noxious stimulation
due to injury, a disease process or the abnormal
function of muscle or viscera). 2 types –
a. Somatic pain - superficial pain
- Deep pain
b. visceral pain - localised pain
- referred pain
Chronic pain : is pain that persists beyond the
unusual course of an acute disease or after a
resonable time for healing to occur.
a. Nociceptive pain
b. Neuropathic pain

9. Acute Pain
•Abrupt onset
•Usually associated
with an acute physcial
condition.
•Self limiting, resolves
as underlying cause
resolves.
•Associated with
sympathetic
responses: increased
BP and pulse,
sweating, blanching of
skin, hyperventilation;
pts appear distressed.
Chronic pain
•Pain may persists for
variety of reasons for more
than 6months duration
•Chronic pain causes
secondary problems: sleep
disturbances, anxiety,
depression, loss of normal
function in work, social,
recreational areas, increased
stress due to these losses
•Effective treatment for
chronic pain should be
multifactorial
•No sympathetic arousal; pts
may not appear distressed.

10. Superficial pain
(from skin &
subcutaneous tissue)
e.g. superficial
cuts/burns, etc.
Well localised and
sharp, pricking,
throbbing or burning
sensation
Deep pain
(from muscles /
bones / fascia /
periosteum)
e.g.
fractures/arthritis/fibr
ositis, rupture of
muscle belly
Dull, aching and less
localised
Somatic pain

11. Nociceptive pain Neuropathic pain
DefinitionPain caused by physiological
activation of pain receptors.
Pain caused by lesion or
dysfunction of the
somatosensory system, esp
the nociceptive pathway.
Mechanism Natural physiological
transduction
Ectopic impulse generation,
among others.
Localisation Local + referred pain Confined to innervation
territory of the lesioned
nervous structure.
Quality of
symptoms
Ordinary painful sensation
(good verbal description)
New strange sensations
(poor verbal description)
Treatment Good response
(conventional analgesics)
Poor – moderate response
(antidepressants,
antiepileptics)
Chronic pain

12. Neurobiology of Neurobiology of
painpain
Transduction : the conversion of the energy from a noxious
thermal, mechanical, or chemical stimulus into electrical
energy (nerve impulses) by sensory receptors called
nociceptors
Transmission : the transmission of these neural signals from
the site of transduction (periphery) to the spinal cord and brain
Perception : the appreciation of signals arriving in higher
structures as pain
Modulation : descending inhibitory and facilitory input from
the brain that influences (modulates) nociceptive transmission.

13. TRANSDUCTIONTRANSDUCTION

14. TRANSDUCTIONTRANSDUCTION
Nociceptive afferents terminate as free nerve endings in skin
and other tissues.
The principal sensory functions consists of:
1)Transduction of external stimuli or internal chemical or
physical stimuli into generator potential
2)Transformation of generator potential into an action
potential.
3)Propogation of the action potential toward the central
nervous system.
4)Release of neurotransmitter and neuromodulators into
the superficial dorsal horn of spinal cord.
5)A site critical for the integration of neural activity.

15. Substances releasedSubstances released
Excitatory effect on nociception:
•Substance P
•Calcitonin gene peptide
•Glutamate
•Aspartate
•ATP
Inhibitory effect on nociception:
•Ach
•Somatostatins
•Enkephalin
•Endorphins
•NA
•Adenosine
•Serotonin
•GABA
•Glycine

16. TransmissionTransmission
Second stage of processing noxious signals.
Impulse relayed in spinal cord brain stem thalamus central
structures of brain (cortex) pain is processed.
Noxious information is relayed mainly via two different types of
primary afferent nociceptive neurons that conduct at different
velocities.

17. PerceptionPerception
The end result of the neural activity of pain transmission
behavioral strategies and therapy can be applied to reduce
pain.
It is believed, pain perception occurs in the cortical
structures—

19. ModulationModulation
Pain modulation means pain perception variabiliaity which is
influenced by :
Endogenous mechanism
Exogenous mechanism
It can be discussed in under following headings:
Spinal modulation of input
- Gate theory of pain
Supra spinal modulation / Descending inhibition pathway
- Role of periaqueductal grey (PAG)
- Role of Nucleus Raphe Magnus (NMR)
Pain modulation by use of opiods neurotransmitters eg:
endorphins, enkaphalin, dynorphin.

20. The gate theory of pain control:The gate theory of pain control:
Proposed by Melzack and wall in 1960’s
Special neurons located in the spinal cord (dorsal horn of
spinal cord SGR) from the gate through which pain
impulses must pass to reach brain
The three variables control the gate
A-delta fibres (fast pain)
C-fibres (slow pain)
A-beta fibres (light touch)
PAIN GATE THEORY
This gate has the ability to block the signals from the A-delta
and C fibres preventing them from reaching the brain.

21. Pain gate theory…..Pain gate theory…..
Gate opened or closed by 3 factors:
1)Activity of pain fibres – opens the gate
2)Activity of other sensory nerves – closes the gate
3)Message from brain
Pain nerves.
Activity opens
the gate
Other sensory
nerves:
Activity closes the
gate (eg rubbing
the affected area)
Message
from brain
Message to
brain
Gate
Transmi
-ssion
nerve
cells

22. Mechanism :Mechanism :
The impulses coming along C fibres  cause the release
of substance P from theses fibres  and tend to open
gate.
While the impulses coming along A-beta fibres  tend to
keep the gate closed by the process of presynaptic
inhibition of C fibres and postsynaptic inhibition of
secondary neurons in dorsal horn.
IF impulses in the C and A-delta fibres are stronger than
the A-beta fibres  gate opens
IF impulses in the A-beta fibres are stronger than C and A-
delta fibres  gate closes.
A-delta fibres are always stronger.

23. CNS
Substania
Gelatinosa
Pain
transmissi
-on
Response
A-beta
fibres
A-delta fibres
C fibres
close
open

24. Supra spinal modulation Supra spinal modulation
This is a specific system that blocks pain transmission in CNS.
Its major constituents are:
Periaqueductal gray (PAG) – in midbrain
Nucleus raphe magnus (NRM) – in upper medulla
Perventricular nucleus – in hypothalamus, near 3
rd
ventricle
Pain inhibitory complex (PIC) – in dorsal horn of spinal cord:
- it consists of multiple short encephalinergic neurons that
terminate on central endings of pain conducting afferent
fibres.
- when stimulated the release of enkephalin/endorphins
cause pre & postsynaptic inhibition of pain transmission i.e, it
prevents the release of substance P from the pain nerve
endings.

25. Analgesia occurs as follows : Analgesia occurs as follows : descendent descendent
antinociceptive system antinociceptive system
Periaqeductal grey area receives neuronal inputs from
thalamus, hypothalamus, cerebral cortex.
PAG projects neurons containing aspartate and glutamate
that stimulate raph magnus nucleus (RMN)
RMN projects sertoninergic neurons, this in addition to
noradrenergic neurons project
from adjacent medulla to dorsal
horn. They block pain signals by
activating PIC

26. Periaqueductal
gray
Glutamate
Raphe Magnus
Nucleus
(Stimulated by #2&3)
7 6
4
3
21
Dorsal Horn:
PIC ACTIVATED
(PIC consists of multiple short
encephalinergic neurons that
terminate on central endings of
pain conducting afferent fibres;
PIC stimulated by #4)
Thalamus
Hypothalamus
Cerebral Cortex
PAI
N
5
Medull
a
Neuronal inputs:
1.Asparate
2.Glutamate
3.Serotoninergic neurons
4.Noradrenergic neurons
5.PIC activated; pain signals blocked
6.Encephalin released
7.Encephallin PREVENTS release ofsubstances P from
pain nerve ending; pre & postsynaptic INHIBITION
of pain transmission

27. Opiod receptor modulationOpiod receptor modulation
Opiod peptides are morphine like substances present in
the body.
They are natural analgesic substances that act by binding
to opiate receptors in analgesics system and dorsal horn
of spinal cord on central ending of pain
Mechanism of opiod neurotransmitter action:
•Endorphins : neurons using endorphins or enkaphalins are
found in PAG where they inhibit GABAnergic
interneurons that normally supress the anti-nociceptor
neurons
•Enkephalin : it is used by interneuron in the lamina II
responsible for inhibiting the lamina I nocioceptor –
specific spinothalamic neurons

28. Dynorphin : in hypothalamus, PAG, reticular formation, and
dorsal horn.
Endogenous morphine : In terminals forming synapses with
neuron having u-opiod receptors in pain modulating
pathways.
Opiod antagonist : Naloxone
-Used to reverse opioid overdose.
-Displaces receptor-bound opioids
-Good for overcoming respiratory and CV depression.

29. Sites and mechanism of pain relief:Sites and mechanism of pain relief:
Block production of inflammatory mediators. E.g.
Aspirin and non-steroidal antiinflammatories.
Sympathectomy can be useful.
Exogenously administration of opioiod like drugs.
Electric stimulation of dorsal column alleviate pain
originating below site of stimulation.
Selective activation of large diameter afferent fibres
by transcutaneous electrical nerve stimulation.
Acupunture
Stimulation of brainstem sites or adminitration of
drugs which can modify sertoninergic or adrenergic
neurons. E.g. Antidepressants.

30. Neuro-anatomy of Neuro-anatomy of ppainain
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

31. Afferent pathwaysAfferent pathways
The afferent portion is composed of:
a) Nociceptors (pain receptors)
b) Afferent nerve fibres
c) Spinal cord network

32. RECEPTORSRECEPTORS
Pain receptors are called nociceptors
Characterised by a high threshold for
activation and encode the intensity of stimulation
by increasing their discharge rates in graded
fashion.
Nociceptors are free nerve endings.
Free nerve endings are distributed everywhere
both somatic and visceral tissues
except brain tissue and lung parenchyma

33. Fast pain
–acute
–pricking type
–well localised
–short duration
–Thin myelinated
nerve fibres are
involved (A delta)
Slow pain
- chronic
–throbbing type
–poorly localised
–long duration
–Unmyelinated
nerve fibres are
involved (c fibres)
Noxious sensation can be broken into two
components:

34. Nociceptors on repeated stimulation display delayed adaptaion /non-adaption ,
sensitization and afterdischarges.
Different types of nociceptors
◦Mechanonociceptor : responds to pinch and pinprick
◦Silent nociceptor : they respond only when inflammatory substances are present.
◦Polymodal mechanoheatnociceptor : most prevalent and responds to excessive
pressure, extremes of temperature and noxious
substances(bradykinine,5HT,histamine)
Two nociceptor receptors has been identified TRPV1 and TRPV2.
Both responds to high temperature. Capsaicin stimulate TRPV1 receptor.
Polymodal nociceptors are slow to adapt to strong pressure and display heat
sensitisation

35. The role of the afferent and efferent
pathways in processing of pain
information
Nociceptive pain
Nociceptors
Location: In muscles, tendons, epidermis, subcutaneous tissue,
visceral organ, they are not evenly distributed in the body (in
skin more than in internal structures)
Stimulators: Chemical, mechanical and thermal noxae
Mild stimulation  positive, pleasurable
sensation 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

36. 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 DH  transmitted to higher parts of the spinal cord
and to the rest of the CNS by spinothalamic tracts
• The small unmyelinated C fibers are responsible for the
transmission of diffuse burning or aching sensations
• Transmission through larger, myelinated A-delta fibers
occurs much more quickly. A-fibres carry well-localized,
sharp pain sensations

37. Efferent analgesic system
• Its role: - inhibition of afferent pain signals
Mechanisms:
- pain afferents stimulates the neurons in periaqueductal
gray (PAG) - gray matter surrounding the cerebral
aqueduct in the midbrain results in activation of efferent
(descendent) anti-nociceptive pathways
- from there the impulses are transmitted through the
spinal cord to the dorsal horn
- there they inhibit or block transmission of nociceptive
signals at the level of dorsal horn

38. The role of the spinal cordThe role of the spinal cord in pain in pain
processingprocessing
 Most afferent pain fibers terminate in the dorsal horn of
the
spinal segment that they enter. Some, however, extend
toward the head or the foot for several segments before
terminating
 The A-  fibers, some large A-delta fibers and small C- fibers
terminate in the laminae of dorsal horn and in the
substantia
gelatinosa

The laminae then transmit specific information (about
burned or crushed skin, about gentle pressure) to 2nd
afferent neuron

39.  2
nd
afferent neurons transmit the impulse from the substantia
gelatinosa (SG) and laminae through the ventral and lateral
horn,
crossing in the same or adjacent spinal segment, to the other
side
of the cord.
 From there the impulse is carried through the
spinothalamic tract to the brain.
The two divisions of spinothalamic tract are known:
1.Neo-spinothalamic tract – It carries information to the mid
brain, thalamus and post central gyrus (where pain is
perceived)
2. Paleo-spinothalamic tract – It carries information to the
reticular formation, pons, limbic system, and mid brain
(more synapses to different structures of brain)

42. Alternative pain pathway:
The spinoreticular tract is thought to mediate
arousal and autonomic responses to pain
The spinomesencephalic tract, descending
pathways, may be important in activating
antinociceptive, because it has some projections to
the periaqueductal gray.
The spinohypothalamic and spinotelencephalic
tracts activate the hypothalamus and evoke
emotional behavior.
 The spinocervical tract ascends uncrossed to the
lateral cervical nucleus, which relays the fibers to
the contralateral thalamus, It is likely a major
alternative pathway for pain.

43. Acute Acute ppainain
Acute pain is a protective mechanism that alerts the
individual to a condition or experience that is
immediately harmful to the body
Onset - usually sudden
This type of pain is typically associated with a
neuroendocrine stress response that is proportional to
the pain’s intensity.
Its most common forms include post-traumatic,
postoperative and obstetric pain as well as pain
associated with acute medical illness
Most forms are self limited or resolve after chemical
mediators that stimulate the nociceptors are removed or
with treatment for days to weeks.

44. increased heart rate, elevated blood pressure

diaphoresis
increased respiratory rate.
 blood sugar
 gastric acid secretion,  gastric motility
pallor or flushing, dilated pupils
 Stress increases catabolic hormones and decreases
anabolic hormones – increase in cortisol, renin,
angiotensin, aldosterone and ADH – sodium water
retension and secondary expansion of extracellular space.
Psychological and behavioural response to acute pain:
fear, general sense of unpleasantness or unease & anxiety
Clinical Manifestation of PainClinical Manifestation of Pain

45. Acute Pain
1. Somatic -
2.Visceral
- True localised
- Referred
Visceral pain
Parietal pain
Visceral pain
Parietal pain
Visceral pain is dull, diffuse, usually midline. Frequently associated
with abnormal sympathetic and parasympathetic activity’
Parietal pain is typically sharp, and often described as a stabbing
sensation that is either localised to area around the organ or reffered
to a distant site.
is superficial coming from the skin or close to the
surface of the body.

46. Referred pain (transferred pain)
Referred pain : Referred pain is pain that is present in an area
removed or distant from its point of origin. The area of referred pain is
supplied by the nerves from the same spinal segment as the actual site
of pain.
Mechanisms involved in referred pain creation:
a) Results from patterns of embroyological development and
migration of tissues.
b) Convergence theory : convergence of impulses from viscera
and from the skin in the CNS:
 Sensory impulses from the viscera create an irritable focus
in the segment at which they enter the spinal cord. Afferent
impulses from the skin entering the same segment are thereby
facilitated, giving rise to true cutaneous pain.

47. C) Facilitation theory:
-The afferent impulses from visceral structures produce
subliminal fringe effects that lower the excitability threshold of
spinothalamic neurons which receive afferent fibres from
somatic areas
-Therefore, any slight activity in the pathways transmitting pain
impulses from somatic regions, and which impulses from
somatic regions and which normally would die out within the
spinal cord, is facilitated thus reaches consciousness levels.

49. Location Cutaneous dermatome
Central diaphragm C4
Lungs T2 – T4
Aorta T1 – L2
Heart T1 – T4
Esophagus T3 – T8
Pancreas and spleen T5 – T10
Stomach, liver and gallbladder T6 – T9
Adrenals T8 – L1
Small intestine T9 – T11
Colon T10 – L1
Kidneys, ovaries and testes T10 – L1
Ureters T10 –T12
Uterus T12 – L2
Bladder and prostate S2 – S4
Urethra and rectum S2 – S4
Patterns of referred pain.

50. Chronic PainChronic Pain
Chronic pain is persistent or intermittent usually
defined as lasting at least 6 months
The cause is often unknown, often develops
insidiously, very often is associated with a sense
of hopelessness and helplessness.
Chronic pain may be nociceptive, neuropathic,
or mixed.

51. Psychological response to chronic pain:
Intermittent pain produces a physiologic response similar to
acute pain.
Persistent pain allows for adaptation (functions of the body
are normal but the pain is not relieved)
Chronic pain produces significant behavioural and
psychological changes:
- depression
- an attempt to keep pain - related behaviour to a minimum
- sleeping disorders
- pre-occupation with the pain
- tendency to deny pain

52. INTENSITY THEORY INTENSITY THEORY
According to this view, pain is produced when any
sensory nerve stimulated beyond a certain level
In other words, pain is supposed to be a non-specific
and depends only on high intensity stimulation.
But the trigeminal system provides an e.g against this
theory. In case of trigeminal neuralgia the patient can
suffer excruciating pain from a stimulus no greater than
a gentle touch provided it is applied to a trigger zone.
Although, the intensity theory is not accepted, it
remains true to say that instensity of stimulation is a
factor in causing pain.

53. Specificity theory (Johannes Specificity theory (Johannes
Muller,1842)Muller,1842)
According to this view, pain is a specific modality equivalent
to vision and hearing etc.
Just there are Meissner corpuscles for the sensation of
touch, Ruffini end organ supposedly for warmth and Krause
end organs supposedly for cold, so also pain is mediated by
free nerve endings.
Ceratin psychological studies have been regarded as
supporting specificity theory. Specialisation is known to
exist in nervous system and there are well known tracts.
But the concept of specific nerve ending is no longer
tenable. The krause and ruffini endings are absent from the
dermis of about hairy skin. So it is certain that these
structures cannot be receptors for cold and warmth.

54. Protopathic and Epicritic theoryProtopathic and Epicritic theory
Head and Rivers (1908) posulated the existence of two
cutaneous sensory nerves extending from the periphery
to the CNS.
The protopathic system is primitive yielding diffuse
impression of pain including extremes of temperature
and is upgraded.
The epicritic system is concerned with the touch
discrimination and small changes in temperature and is
phylogenetically a more recent acquisition.

55. Pattern theory (Goldscheider, Pattern theory (Goldscheider,
1894)1894)
This theory states that pain sensation depends upon
spatio-temporal pattern of nerve impulses reaching the
brain.
According to Woddell(1962) warmth, cold and pain are
words used to describe reproducible spatio-temporal
pattern or codes of neural activity evoked from skin by
changes in environment.
The precise pattern of nerve impulse entering the CNS
will be difficult for different regions and will vary from
person to person because of normal anatomical
variations.

56. TERM DESCRIPTION
Allodynia Perception of an ordinary non-noxious stimulus as pain
Analgesia Absence of pain
Anesthesia Absence of all sensation
Anesthesia dolorosPain in an area that lacks sensation
Dysesthesia Unpleasant or abnormal sensation with or without a
stimulus
Hypalgesia
(hypoalgesia)
Diminished response to noxious stimulation (eg. Pinprick)
Hyperalgesia Increased response to noxious stimulation
Hyperasthesia Increased response to mild stimulation
Hyperpathia Presence of hyperesthesia, allodynia and hyperalgesia
usually associated with overreaction and persistence of
the sensation after the stimulus
Hypesthesia
(hypoesthesia)
Reduced cutaneous sensation (eg, light, touch, pressure,
or temperature)

57. Neuralgia Pain in the distribution of a nerve or a group of nerves
Paresthesia Abnormal sensation perceived without an apparent
stimulus
Radiculopathy Functional abnormality of one or more nerve root