1. ﴿و ما أوتيتم من العلم إلا قليلا﴾
بسم الله الرحمن الرحيم
﴿و ما أوتيتم من العلم إلا قليلا﴾
صدق الله العظيم الاسراء اية 58

2. Assist Prof of Medical Physiology
Physiology of Pain By
Dr. Abdel Aziz M. Hussein
Assist Prof of Medical Physiology

3. Objectives 1. definition of pain 2. types of pain
3. Body reactions or responses to pain
4. perception of pain
5. neural pathways for pain
6. referred and radiating pain
7. modulation of pain perception
8. endogenous analgesia system
9. gate control theory
10. applications of this theory (acupuncture and TENS)

4. Pain Sensation Def : Significance:
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage according to; International association for the study of pain (IASP).
Significance:
Pain is a warning signal for tissue damage. It is the prominent symptom of tissue damage
Pain has a protective function. It initiates protective reflexes that;
Get rid of the painful stimulus.
Minimize tissue injury or damage.

6. Classification of Pain

7. Pain Sensation A) According to its mechanism or cause:
Pain is classified into 3 main types;
1. Physiological Pain
Also called Nociceptive pain
Caused by stimulation of pain receptors by tissues damage e.g. in inflammation
2. Pathological Pain
Also called neuropathic pain
Caused by damage of nerve pathway
3. Psychogenic Pain
In depression and anxiety
Difficult to differentiate whether 2ry to or actual cause of pain

8. Pain Sensation N.B. Neuropathic pain:
according to site of injury is classified into;
Central → Central pain e.g. thalamic infarct
Peripheral → e.g. nerve compression, neuralgias.
Mixed → e.g. post herpetic neuralgia.
Character: neuropathic pain is characterized by burning, tingling, numbness, squeezing, itching, constant +/- intermittent shooting, and electric.

9. Pain Sensation B) According to its duration:
Both nociceptive and neuropathic pains are classified into 2 types;
Acute pain: less than 7 weeks
Chronic pain : more than 7 weeks

10. Pain Sensation C) According to the quality or character :
A pain it is classified into 5 types;
a) Pricking or Cutting Pain:
b) Burning Pain:
c) Aching Pain:
d) Throbbing Pain:
e) Colicky Pain:

11. Pain Sensation 1. Pricking pain 2. Burning pain
Sharp and localized pain.
Of skin origin (mainly)
e.g. in pricking or cutting the skin by sharp object
2. Burning pain
Less well localized, has unpleasant burning nature.
Usually of skin origin
Caused by wide spread irritation of skin

12. Pain Sensation 3. Aching pain 4.Throbbing pain 5.Colicky pain
disagreeable pain of dull- aching nature
More diffuse and felt coming from deeper tissues e.g. rheumatic pains
4.Throbbing pain
Fluctuation of its intensity with arterial pulsations
localized inflammation in deep tissues e.g. abscess
5.Colicky pain
Comes in cramps, so it has a colicky nature, e.g. intestinal colic and ureteric colic
Spasm of smooth ms in the walls of hollow viscera

13. Pain Sensation Cutaneous pain Deep pain Visceral pain
D) According to site of origin: 3 types;
Cutaneous pain
Pain comes from skin and subcutaneous tissues
Usually pricking or burning pain
Deep pain
Pain comes from structures deep to the skin e.g. skeletal muscle, joints, and tendons
Usually dull aching or throbbing
Visceral pain
Pain comes from internal viscera e.g. stomach
Usually colicky or dull aching

14. Body Reactions to Pain

15. Body Reactions to Pain 1) Somatic reactions: a) Withdrawal reflex :
It occurs in cutaneous pain
This is a protective reaction which get rid of injurious agent
b) Reflex spasm of nearby muscle:
It occurs in deep pain
It immobilize pained parts to decrease pain sensation
c) Reflex spasm of overlying muscle:
It occurs in visceral pain
It produce guarding rigidity of abdominal muscle (guarding reaction)

16. Body Reactions to Pain 2) Autonomic reactions:
Mild and moderate cutaneous pain → sympathetic stimulation → ↑ heart rate and ABP (pressor reaction)
Sever cutaneous, deep, and visceral pain → parasympathetic stimulation →↓ HR and ABP (depressor reaction)
3) Emotional or psychogenic reactions:
In the form anxiety, fear, crying, and depression
These reactions vary:
From person to person on exposure to similar pain stimuli.
In the same person according to his emotional state:
-Worry about the cause of pain augment the feeling of pain.
Strong emotional excitement & sever physical exertion may block the feeling of pain.
Thus, seriously wounded soldiers in a battlefield suffer little or no pain till the battle is over.

17. Body Reactions to Pain 4) Cutaneous hyperalgesia: It is 2 types;
SECONDARY
PRIMARY
In healthy skin area around red area
In the red area
Site:
It duration is much shorter than that of 1ry hyperalgesia
It develops within 30 to 60 minutes and lasts for several hours or days after injury.
Duration
When a noxious stimulus is applied, the pain felt is more severe than usual.
When non-noxious stimuli such as touch or mild warming are applied they cause pain.
Characteristics:
Convergence -Facilitation theory:
-No lowering of the pain threshold
-The pain impulses from the area of 1ry hyperalgesia facilitates (↑ed excitability) those from the area of 2ry hyperalgesia.
It is due to lowered threshold of pain receptors in the red area due to local axon reflex
Mechanism:

19. Area of injury Area of redness Healthy skin Antidromic impulse
Secreting substance P

20. Convergence facilitation
Area of injury
Area of redness
Healthy skin
Convergence facilitation

21. Pain Perception

22. Pain Perception
Pain sensation
Painful stimulus

24. Pain Receptors 1)Types:
They are morphologically similar but functionally they are specific
Morphological types: are specific free nerve endings
Functional types: classified according to their adequate stimulus into:-
1) Mechanical Pain Rs:
Respond to strong mechanical forces, such as cutting, or pricking
2) Thermosensitive pain Rs:
Respond to excessive changes in temp. (above 45°C and below 10°C).
3) Chemical Pain Rs: respond to noxious chemical stimuli.
4) Polymodal Pain Rs:
Respond to a combination of mechanical, thermal, and chemical noxious stimuli

25. Pain Receptors 2)Distribution:
Pain Rs are found in most tissue of the body.
a) Abundant in the skin and some internal tissue such as the periosteum, arterial wall, joint surfaces, and the dura of the tentorium cerebelli.
b) Few in deep tissues and all viscera. So, for pain to occur, painful stimulus must by intense and widespread. The deep & visceral pain is poorly localized.
c) Brain itself and the parenchymal tissues of the liver, kidneys, and lungs have no pain receptors “pain insensitive structures”
N.B.: Serious diseases in these organs don’t produce pain till they extend to a pain sensitive structure like arterial wall or serous covering.

26. Pain Receptors Tissue damage 3) Mechanism of stimulation:
Chemical stimuli
Strong acids or Alkalies
Mechanical stimuli
Cutting or pricking
Thermal stimuli
temp. > 45 C and < 10 C
Tissue damage
1st class
K ions, Histamine, Serotonin, and Bradykinin
Release of Pain Producing Compounds (PPS)
2nd class
PGE2, leukotriens and Substance P
Sensitize the pain Rs by lowering its threshold to stimuli
Directly stimulate
Pain Receptors

27. Tissue Damage
Direct stimulators
Sensitizers

29. Pain Receptors 4) Adaptation:
Pain Rs do not adapt to continuing noxious stimuli
This serves a protective function to keep the individual trying to remove the damaging stimulus or to get away from it.

30. Neural Pathways of Pain

31. Fast Pain Pathway Pathway: Neospinothalamic tract
A) 1st order neuron :
A delta afferent fibers
End in lamina I of dorsal horn of spinal cord
B) 2nd order neuron :
Axons of neurons lamina I of dorsal horn of spinal cord cross the opposite side in front of central canal and ascend as neospinothalamic in spinal cord and as spinal leminiscus in brain stem
End in posteroventral nucleus of thalamus (PVNT)

32. Fast Pain Pathway Pathway: C) 3rd order neuron :
Axons of neurons of PVNT ascend in sensory radiations
End in primary somatic sensory area (area 3,1,2)
Note:
The chemical transmitter released at the central end of A delta fibers that carry fast pain is glutamate

33. Receptors Free nerve endings Lateral spinothalamic tract
Fast Pain Pathway
PVNT
Sensory Radiations
Spinal Leminiscus
Lamina I
A delta
Receptors Free nerve endings
Lateral spinothalamic tract

34. Slow Pain Pathway Pathway: Paleospinothalamic tract
A) 1st order neuron :
C afferent fibers
End in lamina II and III (called substantia Gelatinosa of Rolandi SGR) of dorsal horn of spinal cord
B) 2nd order neuron :
Axons of neurons SGR of dorsal horn of spinal cord cross the opposite side in front of central canal and ascend in spinal cord and as;
Spinoreticular tract end in RF of MO and Pons
Spinotectal tract end in PAG areas of midbrain
Paleospinothalamic tract end in non specific thalamic nuclei (intralaminar and midline)

35. Slow Pain Pathway Pathway: C) 3rd order neuron :
Axons of neurons from RF and NSTN of thalamus ascend in sensory radiations
Terminate diffusely in all areas of the cerebral cortex
Note:
The chemical transmitter released at the central end of c fibers that carry fast pain is substance P

36. Paleospinothalamic tracts
All cortical areas
Non-specific nuclei of thalamus
Periaqueductal gray area (PAG) in midbrain
Reticular formation
In MO and Pons
SGR
Laminae II, III
Afferent
C fibers
Receptors
Free nerve endings
Paleospinothalamic tracts

37. Comparisons Between Slow and Fast Pain
Chronic (Slow)
Acute (Fast)
Skin, deep tissues, and viscera
Skin only
Source
All types
Mechanical and thermal
Stimulus
Burning
Pricking
Quality
One or more seconds after stimulation
Within 0.1 sec after stimulation
Onset
Long (few minutes)
Short (one second)
Duration
Diffuse
Well –localized
Localization C
A-delta
Afferent
Paleospinothalamic tract
Neospinothalamic tract
Tract
Thalamus
Cerebral cortex
Centre
Substance P
Glutamate
Chemical trans.

38. Radiating and Referred Pain

39. Referred Pain Def: Site of referral is determined by dermatomal rule:
Referred pain is pain felt away from the site of its origin
Radiating pain is pain appear to migrate away from the its original site
Referred pain is a part of radiating pain
N.B.
Visceral pain usually referred, deep pain may be referred but cutaneous pain never referred
Site of referral is determined by dermatomal rule:
The pain from a viscera is referred to a somatic structure (skin or deep structure) which were developed in the same embryonic segment and supplied by the same dorsal root ganglia.
Abnormal sites are due to migration of viscera.

41. Referred Pain Mechanism : Convergence Projection Theory:
Afferents pain fibers from skin area and diseased viscera converge on the same 2nd order neuron and finally stimulate the same cortical neuron
The cortex project (feel) pain as it is coming from the skin because the sensory cortex is accustomed to receive pain from the skin
Skin is the commonest site of pain
Convergence may occurs also at the level of thalamus or sensory cortex

43. Modulation of Pain Perception

45. Pain Control System There is endogenous analgesic system as proved by:
Stress analgesia e.g. soldiers wounded by the heat of the battle may feel no pain until the battle is over.
The pain felt from an injured area is reduced when the skin around the injured area is rubbed or stroked.
Morphine injected in minute doses in experimental animals in the third ventricle of the brain produce marked analgesia.
This Pain Control System can modulate pain sensation (mainly inhibitory) by release of endogenous opiate like (opioid) peptides such as encephalins, endorphins
It cause both presynaptic and postsynaptic control of nociception in the dorsal horn via enkephalin release which inhibits release of substance P, transmitter at pain nerve endings

46. Endogenous Analgesia System
1) Def,
System which control pain transmission in CNS or inhibit pain transmission i.e. endogenous analgesia system
2) Sites:
Periventricular area of hypothalamus
Periaqueductal area (PAG) around aqueduct of sylivus in midbrain and Pons
Nucleus raphe magnus (NRM) AND Nucleus reticularis paragigantocellularis (NRPG) in lower Pons and upper medulla
Pain inhibitory complex (PIC): interneuron in dorsal horn of spinal cord

48. Endogenous Analgesia System
3) Neurochemistry:
This system act through the release of endogenous opioid peptides which act on opiate receptors.
Opioid peptides:
They include 3 groups; enkephalins, endorphins and dynorphins.
Opiate Receptors:
3 types of opiate receptors : delta (δ), kappa (κ), and muta (μ).
Enkephalins bind with the delta (δ) receptors
Endorphins bind with the muta (μ) receptors
Dynorphins bind with the kappa (κ) receptors.
These receptors can be blocked by naloxone, which is a morphine antagonist

49. Natural (physiological) Stress induced analgesia
Activation of the Pain Control System
Clinical (Experimental)
Natural (physiological)
1- Electrical stimulation of certain regions of pain control system
Exposure to severe stress, particularly when associated with strong emotional excitement.
2- Local application of opiates (such as morphine) at particular regions in the nervous system.
(pharmacological analgesia)
Stress induced analgesia

50. Stress Periventricular nucleus of hypothalamus
Endorphins ++
Periaqueductal gray area
Stress
Encephalin ++
Nucleus raphe magnus
Serotonin ++
Ascending pathway
1st order neuron of pain
Encephalins --
Substance P
Posterior horn of spinal cord

51. Endogenous Analgesia System

52. Gate Control Theory

54. Gate Theory of Pain Sites:
The sites of synapses along the pain pathway are considered as gates through which pain transmission can be;
Facilitated (if the gate is open) or
Blocked (if the gate is closed).
Sites:
The main pain gates are:
1- Spinal gate: at the SGR.
2- Brain stem gate: at the nuclei of reticular formation.
3- Thalamic gate: At neurons of PVLNT & intalaminar thalamic nuclei.

55. 3 2 1

57. Spinal Gate At spinal gate pain transmission is blocked by;
Descending inhibitory impulses through the pain control system activating enkephalin-secreting interneuron
Stimulation of the large diameter nerve fibers (A delta and A beta) terminating peripherally in mechanoreceptors, such as tactile receptors or proprioceptors (A beta), and pricking pain fibers (A delta).

58. Gate Theory of Pain

59. Spinal Gate
This may explain why simple maneuvers such as rubbing the skin (thus exciting tactile and pressure receptors), near a painful area is often effective in relieving certain types of pain → A beta
Also block of pain by acupuncture (A delta fibers)

60. Pain Control by Rubbing
Interneuron
Rubbing of the skin
A beta fibers
Pain C fiber
Painful stimuli

61. Acupuncture Interneuron A delta fibers Pain C fiber Painful stimuli

62. Applications of Gate Control Theory
This theory provides basis for various methods of pain relief
Massaging a painful area
Applying irritable substances to a painful area (counter-irritation)
Transcutaneous Electrical Nerve Stimulation (TENS)
Acupuncture ?

63. Acupuncture Mechanism:
Acupuncture has been practiced in China for more than years as a method for pain relief.
Mechanism:
1- Needles in appropriate body regions are thought to excite certain sensory neural pathways which feed into the brain stem centers (such as the PAG) involved in the pain control system, with release of endogenous opioid peptides.
2- Simultaneous suppression of pain transmission at the spinal pain-gate by acupuncture

65. TENS
Def.,
TENS is any stimulating device which delivers electrical currents across the intact surface of the skin
Mechanism:
TENS causes relieve of pain by activate large diameter ‘touch’ fibres (Aβ) without activating smaller diameter nociceptive fibres (Aδ and C) this causes;
1- Excitation of certain sensory neural pathways which activate PAG area involved in the pain control system, with release of endogenous opioid peptides.
2- Simultaneous suppression of pain transmission at the spinal pain-gate by acupuncture

67. TENS

69. Modulation of Pain Perception
Conditions that closes the Gate
Conditions that open the Gate
medications
Counter stimulation, e.g. massage, heat
Extent of injury
Extra activity
Physical conditions
Relaxation
Positive emotion
Depression, tension
Anxiety, worry
Emotional conditions
Distraction
Involvement in life activity
Focusing on pain
Mental conditions

70. THANKS