The seminar explains in detail the physiology and the pathological mechanism behind the pain related to irreversible pulpal inflammation.

1. GOODMORNING

2. Pathophysiology of
Pain in Irreversible
Pulpitis
AMAL SINGH RANA

3. Contents
Pain
Inflammation
Irreversible pulpitis
Anatomy of dental innervation
Transmission of pain

4. “An unpleasant sensory and emotional experience associated with actual or potential tissue
damage, or described in terms of such damage.”
Always Subjective
2019
Pain

5. Types of Pain
Pain
• Nociceptive pain
• Neuropathic pain
• Heterotrophic pain ( Referred pain )
• Peripheral sensitization
• Central sensitization Pathways of pulp, Cohen, 11th ed, Pg.no 554

6. 1994
9 Major categories
33 Subcategories

7. Classification

8. Inflammation is a protective response involving cells , proteins and other mediators that is intended to eliminate
the initial cause of cell injury.
Inflammation
Clears Infection
Initiate repair
Damages normal tissue
Severe
Prolonged
Auto immune diseases

9. Types
Feature Acute Chronic
Onset Fast Slow
Cellular infiltrate Neutrophils Macrophages, Lymphocytes,
Monocytes
Tissue injury Mild Severe
Signs More
prominent
Less prominent
Basic Pathology, Robbins, 7th ed., Pg.no 30

10. Reaction
Vascular changes
Vasodilation
Increased vascular permeability
Basic Pathology, Robbins, 7th ed., Pg.no 33

11. Cellular Changes
Leukocyte Activation
Phagocytosis

12. Inflammatory Mediators
• Histamine
1
• Serotonin
2
• Prostaglandin
3
• Leukotrienes
4
• Platelet activating factor
5
• Reactive oxygen species
6
• Cytokines
7
• Neuropeptides
8
Cell-Derived
Basic Pathology, Robbins, 7th ed., Pg.no 45

13. • Complement Activation (c3a, c5a, c3b, c5b)
1
• Kinins (Bradykinin)
2
• Fibrinolysis system (Proteases)
3
Plasma-Derived
Basic Pathology, Robbins, 7th ed., Pg.no 45

14. Origin Mediators Sources
Histamine Mast cell, basophils, platelets
Serotonin Platelet
Prostaglandins Mast cell, leukocytes
Leukotrienes Mast cell, leukocytes
Platelet activating factors Mast cell, leukocytes
Reactive oxygen species Leukocytes
Cytokines Activated macrophages
Basic Pathology, Robbins, 7th ed., Pg.no 45

15. Functions
Mediators Functions
Histamine Vasodilation, increased vascular permeability
Serotonin Vasoconstriction
Prostaglandins Vasodilation, pain, fever
Leukotrienes Increased vascular permeability, chemotaxis, leukocyte adhesion/activation
Platelet activating factors Vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis
Reactive oxygen species Killing of microbes, tissue damage
Cytokines Local (Endothelial activation) , systemic (Fever, Hypotension)
Mediators Functions
Complements Leukocyte chemotaxis and activation, direct target killing, vasodilation
Kinins Increased vascular permeability, smooth muscle contraction, vasodilation, pain
Proteases Endothelial activation, leukocyte recruitment
Basic Pathology, Robbins, 7th ed., Pg.no 45

16. Normal Anatomy of
Dental Innervation

17. PULP
Sensory Autonomic
Conduction of noxious stimulus Regulation of blood flow
Trigeminal ganglion via CN V Superior cervical ganglion with ICA
to join CN V

18. Nerve fibres (Types)
A-Fibers C-Fibers
Fast Conducting Slow Conducting
Myelinated
Unmyelinated
Sharp shooting pain Dull Aching pain
Most sensory fibers being unmyelinated within the dental pulp, the majority have a myelinated origin

19. Subtypes & Function
70 to 80% ( Unmyelinated )

20. Distribution
A-Fibers
Entry – Apical Foramen
Pulp Horns
Cervical area
Radicular Dentin

21. Unmyelinated fibers
Pulp core
Plexus of Rashkow
Extension into dentinal tubules

22. Clinical Implication
Placement of an EPT electrode
Incisal third of an anterior tooth
Mesio-buccal cusp of a molar

23. Pattern of Distribution
Attributed to the dependence of nerve fiber on different “Neurotrophin and Neurotrophic factors”
Nerve growth factor
Brain derived neurotrophic factor
Neurotrophin 3 and 4
Glial cell derived neurotrophic factor
Ciliary neurotrophic factor
A fibers – Glial cell derived neurotrophic factor ( Close to Coronal pulp )
C fibers and sympathetic nerve fibers – Nerve growth factors
Ingles Endodontics, 7th ed, Pg.no 203

24. Neuropeptides
Nerve fibres
Peptidergic Non-peptidergic
A-fibers and C-fibers contain
Substance P and CGRP

25. Nerve fibers (Functions)
One
• Regulation of pulpal blood flow
Two
• Regulation of pulpal immunity
Three
• Transmission of pain

26. Regulation of blood flow
Under normal condition : Pulp is adequately perfused
Nutrient and oxygen supply
Maintain normal tissue pressure
In tissue injury and inflammation : Activation of sympathetic and Sensory nerve fibers
Sympathetic Activation Release of NPY & NE
Sensory stimulation Release of CGRP & SP
Reduced blood flow
Changes in vascular permeability

27. Immune regulation
• NKA
• VIP
• CGRP
• SP
Phagocytosis
Histamine
release
Proliferation
of T-
Lymphocytes
Limits the size
of periapical
lesion
J Endod. 2003;29(9):557–558.
Peptides. 1985;6(2):107–111
Bone. 2000;27(6):803–810

28. Origin of pain
TRANSDUCTIO
N
CONDUCTION
TRANSMISSIO
N
PERCEPTION
Process by which noxious stimuli are
converted into electrical activity in
appropriate nerve endings.
Nociceptive information is carried
from nerve endings to central
terminal of neurons
Neural events that carry nociceptive
impulses across synaptic junctions from
one neuron to another
1st 2nd 3rd order neurons
Final process in subjective
experience of pain
Occurs in cerebral cortex
Highly variable between peoples

29. Oral and facial pain, Okeson, 7th ed., Pg.no 34

30. Process of transmission
• Sensory Nociceptors
• Post ganglionic
sympathetic-efferent
Detection
• SENSORY NUCLEI
in Medullary
dorsal horn
Processing
• Trigemino-thalamic tract
Thalamus
• Cerebral cortex
Perception
First order neurons
Second order neurons
Third order neurons
( Thalamocortical tract )

31. Detection
Distal terminal of nerves haves “SENSORY RECEPTORS“
Exteroreceptors
Propioreceptors
Interoreceptors
Nociceptors
Merkel endings, Meissner’s, Ruffini’s, Krause’s corpuscles
Muscle spindles, golgi tendon organs, pacinican’s corpuscles,
Periodontal mechanoreceptors
Visceral system
Detects mechanical, thermal, chemical stimuli

32. Detection
Thermal
Mechanical
Chemical
Polymodal afferents G-protein coupled receptors
( A-delta fibres , C-fibres ) Transient receptor potential vanilloid 1
Toll-Like Receptors
On Activation….,
GPCR
GS
Gi/0
G-Alphaq/11
GS Gi/0 G-Alpha q/11
Activates adelylate
cyclase
Increases cAMP
Nociceptor
Stimulation
Decreases cAMP
Nociceptor
Inhibition
Activates
Phospholipase-C
Nociceptor
senstization
Ingles Endodontics, 7th ed, Pg.no 204–05

33. TRPV-1
Detects chemical and thermal stimuli ( more than > 43°C )
First targets that detect external stimuli and mediate the transmission of pain.
TOLL-LIKE RECEPTORS ( Pattern recognition receptors )
Recognize antigens produced by microorganisms
Lipopolysacchrides
Lipo-techoic acid
( Gram –ve )
( Gram +ve )
Sensitization of receptors
Reduced threshold
Spontaneous pain
Ingles Endodontics, 7th ed, Pg.no 205–06

34. Peripheral Sensitization
Repeated exposure to noxious stimuli
Reduced threshold
Sensitization of A & C-fibres
Hyperalgesia
Allodynia
Spontaneous pain
Inflammatory Mediators
Prostaglandins
Leukotrienes
Substance P
Interleukin 1
Pathways of pulp, Cohen, 11th ed, Pg.no 550

35. Hyperalgesia
Allodynia
Characterstics
Spontaneous pain
Reduced pain threshold
Increased response to painful stimuli
Perception of pain in response to
non-noxious stimuli
Symptoms
Throbbing pain
Increased response to electric/thermal test
Symptoms
Mechanical allodynia Thermal allodynia
Pain on chewing
Pain on eating

36. Neuronal Plasticity
Plasticity of interdental nerve fibers are implicated in dental injury
Modifying gene expression Changing cytochemical phenotype
Low Intensity injury
Increases primary afferent fibres
SPROUTING
Ingles Endodontics, 7th ed, Pg.no 206

37. Expression of nerve growth factor
NGF is synthesized by the fibroblast coronal to cell rich zone
Maximal sprouting = Pulp horns
Neuronal
sprouting
Increased in no. of
neuropeptides
Neurogenic
inflammation
Pathways of pulp, Cohen, 11th edition, Pg.no 552

38. Processing ( Central Nervous System )
Trigeminal spinal tract nuclear complex ( Medulla )
Subnuclei Caudalis
Subnuclei Interpolaris
Subnuclei Oralis
Receives most of the nociceptive inputs
Also known as “Medullary dorsal horn”
Pathways of pulp, Cohen, 11th ed, Pg.no 554

39. 50%
Neurons of caudalis receive convergence
of sensory input from wide range of
cutaneous and deep structures
Patient perceives pain in particular teeth that
actually originates from different
tooth/structure
Pathways of pulp, Cohen, 11th ed, Pg.no 554

40. Second order neurons
Thalamus
Medullary
dorsal
horn
( Transmission neurons )
Low threshold
mechano-sensitive
• Light touch
• Pressure
• Propioreception
Nociceptive specific
• Noxious stimuli
Wide dynamic range
• Noxious stimuli
• Non-noxious
stimuli
TYPES
Oral and facial pain, Okeson, 7th ed., Pg.no 56

41. Second order neurons
Anterolateral spinothalamic tract
Neospinothalamic
A-Delta fibres
Paleospinothalamic
C-fibres
Leminiscal system
Light touch
Pressure
Propioception
Oral and facial pain, Okeson, 7th ed., Pg.no 57

42. Central Sensitization
Hyperalgesia and Allodynia
Intense and repeated stimulus
Release of Glutamate
Activation of NDMA
glutamate receptor
Excitation of nociceptive neurons
Increase responsiveness of nociceptive neurons of
CNS due to peripheral stimulation

43. Third order neurons
3rd
order
neurons
Thalamus Cerebral cortex
( Thalamocortical tract )
Starts from ventral posteromedial nucleus
Oral and facial pain, Okeson, 7th ed., Pg.no 58

44. 45%of somato-sensory cortex is
dedicated to face, mouth and throat
Oral and facial pain, Okeson, 7th ed., Pg.no 35

45. Pain in irreversible pulpitis
A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is
incapable of healing
Spontaneous pain
Pain on Chewing
Pain due to thermal changes
Sharp shooting pain

46. CAUSES

47. Activation or Sensitization of Nociceptive afferent fibres by inflammatory mediators
Mediators Effect on nociceptors
Histamine Activation
Serotonin Activation
Bradykinin Activation
Prostaglandin Sensitization
Leukotrienes Sensitization
Substance P Sensitization
Pathways of pulp, Cohen, 11th ed, Pg.no 550

48. Spontaneous pain
Occurs due to Hyperalgesia and Allodynia
Contributing mechanisms
Concentration and type of inflammatory
mediator
Tissue pressure
Neuronal Sprouting
Peripheral sensitization
Central sensitization
Pathways of pulp, Cohen, 11th ed, Pg.no 550

49. Sharp Shooting pain
Key to dental pain mechanisms are “ voltage-gated sodium channels ” (Nav)
Isoform within pulp
Nav1.7 Nav1.8
Upregulated in painful teeth
when compared to normal one
Forms clusters in unmyelinated
segments of myelinated axons
Promotes faster
conduction of an impulse
Ingles Endodontics, 7th ed, Pg.no 206

50. Depolarization of nerve at lower stimulus
Sensitization
of Nav
channels
Inflammation
Release of
prostaglandins

51. Pain on Thermal changes ( Thermal Allodynia )
A hallmark of symptomatic irreversible pulpitis pain.
Expression of thermoreceptors
Pulp
Fibroblasts
TRPA1
TRPM2
TRPM8
Odontoblasts
TRPV 1
TRPV 2
TRPV3
TRPA1
TRPM8
TRPV1 – HEAT stimuli
TRPM8 – Cold stimuli
Ingles Endodontics, 7th ed, Pg.no 208

52. Pain on Biting ( Mechanical Allodynia )
• Micro-organisms and their toxins
• Activates pulp mechanoreceptors
1
• Microbes and their toxins
• Activates peri-radicular mechanoreceptors
2
• Expression of pulpal nociceptors
• Activates central sensitization
3
Odontoblasts expresses TRPV4 & TRPM3
Presence of A-Delta fibres
Ruffini’s endings
Ingles Endodontics, 7th ed, Pg.no 208

53. Pain relief on cold application

54. Hydrodynamic theory ( M. Brännström in 1966 )
Rapid movement
of fluid into the
dentinal tubules.
Thermal
stimulation
Heat
Fluid flow towards pulp
Cold
Fluid flow away from pulp
Pathways of pulp, Cohen, 11th ed, Pg.no 547

55. Acute Inflammation
Accumulation of Neutrophils
Exudation of fluid from vessels
Edema = Increased intra-pulpal pressure
Pain
Measurement of human intra-pulpal pressure and its response to clinical variables, oral surg oral med oral pathol,1965(5) Pg.no655-58

56. Cold application Vasocontriction Decreased intra-pulpal pressure
PAIN REILIEF

57. Thank You