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 and
Pain Control System By
Dr. Abdel Aziz M. Hussein
Assist Prof. of Medical Physiology

3. Pain Sensation
Def :
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage
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.

5. Classification of Pain

6. Occurs at the time of injury
Pain Sensation
A) According to its duration:
Pain is classified into 2 types;
1. Acute
Fast or epicritc
Occurs at the time of injury
2. Chronic
Slow or protopathic
After injury

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

8. Pain Sensation 1. Physiological Pain 2. Pathological Pain
C) According to its mechanism or cause:
Pain is classified into 2 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 e.g. sciatica

9. Pain Perception

10. Pain Perception
Pain sensation
Painful stimulus

11. Pain Receptors 1) Morphology: are specific free nerve endings
Pain Rs are morphologically similar but functionally they are specific
1) Morphology: are specific free nerve endings
2) Highly specific i.e. respond to tissue damage only
Classified according to their adequate stimulus into:-
a) Mechanical Pain Rs:
Respond to strong mechanical trauma e.g. cutting
b) Thermosensitive pain Rs:
Respond to excessive changes in temp (above 45°C and below 10°C).
c) Chemical Pain Rs: respond to noxious chemical stimuli.
d) Polymodal Pain Rs: respond to a combination of mechanical, thermal, and chemical noxious stimuli

12. Pain Receptors 3) Distribution:
Abundant in the skin and some internal tissue such as the periosteum, arterial wall, joint surfaces, and the dura of the tentorium cerebelli.
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.
Brain itself and the parenchymal tissues of the liver, kidneys, and lungs have no pain receptors “pain insensitive structures”

13. Pain Receptors 4) Threshold :
It is the lowest intensity of injurious agent needed to stimulate the pain receptors to cause pain sensation
Pain receptors are of high threshold: the pain receptors needs sufficient degree of tissue damage to be stimulated.
Measured by;
By pricking the skin with a pin at measured levels.
By compressing the skin against hard objects.
Thermal method (more accurate) (45 C)

14. Pain Receptors 5) Adaptation:
Slowly adapting receptors even non adapting receptors
This is very important because it directs the subject to get rid of the injurious agent

15. Pain Receptors 6) Mechanism of stimulation: Tissue damage
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

17. Neural Pathways of Pain

19. 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)

20. 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

21. 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

22. 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)

23. 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

24. 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

25. Significance of Pain Pathways
Paleospinothalamic
Neospinothalamic
a) Continuously inform the C.N.S about the presence of tissue damage → direct the person to remove the injurious agents.
a) Rapidly inform the C.N.S about the injurious agent → initiate rapid protective reflexes as flexion withdrawal reflex.
b) Strong arousal state due to potent activation of RAS
c) Initiation of the emotional & autonomic reactions, through RF
b) Determines accurately the site “locality” of the painful stimuli.

26. Comparisons Between Slow and Fast Pain
Chronic (Slow)
Acute (Fast)
Skin, deep tissues, and viscera
Skin only
Source
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.

27. Radiating and Referred Pain

28. Referred Pain
Def:
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 e.g. sciatic pain
Referred pain is a part of radiating pain
N.B.
Visceral pain usually referred, deep pain may be referred but cutaneous pain never referred

29. Referred Pain 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.

31. Pain
Injury

32. Referred Pain Mechanism : Convergence Projection Theory:
Afferents pain fibers from skin area and diseased viscera converge on the same neuron of SGR 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
Convergence may occurs also at the level of thalamus or sensory cortex

33. Neuropathic Pain
Def. :
Is a chronic type of pain caused by damage to or pathological changes in the nerve fibers either in the peripheral or central nervous system.
Examples:
Central → Central pain e.g. thalamic infarct
Peripheral → e.g. nerve compression e.g. Sciatica (Lesley Smith), neuralgias and neuropathy
Mixed → e.g. post herpetic neuralgia.

34. Nociceptive pain
Neuropathic Pain

35. Neuropathic Pain Characters:
1. Described as tingling, numbness, , burning or shooting pain.
2. It occurs in bouts or paroxysms.
3. Usually accompanied by hyperalgasia and allodynia.
4. Hardly to be treated.
5. Partially responsive to opioid therapy
6. May respond to tricyclic antidepressant

36. Pain Control System

39. Pain Control System 1) Def,
System which control pain transmission in CNS or inhibit pain transmission i.e. endogenous analgesia system
N.B
The activity of this system differs from one person to another and from time to time in the same person.

40. 2) Components : 1. Periventricular hypothalamic area
2. Periaqueductal area (PAG)
3. Nucleus reticularis paragigantocellularis (NRPG) and locus cerulus
3. Nucleus raphe magnus (NRM)
4. Pain Inhibitory Complex (PIC)

41. 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 mu (μ).
Enkephalins bind with the delta (δ) receptors
Endorphins bind with the mu (μ) receptors
Dynorphins bind with the kappa (κ) receptors.
These receptors can be blocked by naloxone, which is a morphine antagonist

42. 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

43. Mechanism of Stress Induced Analgesia

44. Posterior horn of spinal cord
Ascending pathway
1st order neuron of pain
Glutamate Substance P
Posterior horn of spinal cord

45. Posterior horn of spinal cord
Limbic system RF
Hypothalamus
Cerebral cortex
PAG
Severe stress
Strong emotions
Encephalin ++
NRM LC
Serotonin ++
Noradrenaline ++
Ascending pathway
1st order neuron of pain
Encephalins --
Glutamate Substance P
Posterior horn of spinal cord

46. Action of encephalins at PIC

47. Gate Control Theory

49. Gate Theory of Pain Sites: Was proposed by Melzack and Wall in 1965.
States that, 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.

50. 3 2 1

52. 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).

53. Gate Theory of Pain

54. 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)

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

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

57. 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

58. 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

60. 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

62. TENS

64. 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

65. THANKS