Physiology lecture - Pain perception, content is mainly taken from Human Physiology - From Cells to Systems, Eighth Edition by Lauralee Sherwood

2. PAIN PERCEPTION AND HEADACHES
DR. M. ATHAR ABDULLAH
M. PHIL PHYSIOLOGY PGT
ISLAMIC INTERNATIONAL MEDICAL COLLEGE
FROM SHERWOOD 8th edition

3. LEARNING OBJECTIVES
At the end of this presentation M. Phil PGTs should be able to:
• Describe the different types of pain receptors
• Describe the different types of pain pathways
• Differentiate between slow and fast pain
• Explain the process of pain signal transmission
• Describe the body analgesia system

4. INTRODUCTION
• Pain is primarily a protective mechanism meant to bring to
conscious awareness tissue damage that is occurring or is about to
occur
• Because of their value to survival, nociceptors do not adapt to
sustained or repetitive stimulation
• Storage of painful experiences in memory helps us avoid potentially
harmful events in the future

5. Unlike other somatosensory modalities,
• The sensation of pain is accompanied by motivated behavioral
responses (such as withdrawal or defense) and emotional reactions
(such as crying or fear)
• The subjective perception of pain can be influenced by other past or
present experiences (for example, heightened pain perception
accompanying fear of the dentist)
• Therefore pain is a private, multidimensional experience

6. PAIN RECEPTORS
Nociceptors
Mechanical
Mechanical damage
such as cutting,
crushing, or
pinching
Thermal
Temperature
extremes, especially
heat
Polymodal
Respond equally to all
kinds of damaging stimuli,
including irritating
chemicals released from
injured tissues

7. ROLE OF PROSTAGLANDINS
• All nociceptors can be sensitized by the presence of prostaglandins,
which greatly enhance the receptor response to noxious stimuli
• Tissue injury, can lead to the local release of prostaglandins
• These chemicals act on the nociceptors’ peripheral endings to lower their
threshold for activation
• Aspirin-like drugs inhibit the synthesis of prostaglandins, accounting at
least in part for the analgesic (pain-relieving) properties of these drugs

8. AFFERENT PAIN FIBERS
Pain impulses originating at nociceptors are transmitted to the CNS via
one of two types of afferent fibers:
• Signals arising from nociceptors that respond to mechanical damage
such as cutting or to thermal damage such as burning are
transmitted over small, myelinated A-delta fibers at rates of up to
30 m/sec (the fast pain pathway)

9. AFFERENT PAIN FIBERS
• Impulses from polymodal nociceptors that respond to chemicals
released into the ECF from damaged tissue are carried by small,
unmyelinated C fibers at a slower rate of 12 m/sec or less (the slow
pain pathway)

10. Think about the last time you cut or burned your finger. You undoubtedly
felt a sharp twinge of pain at first, with a more diffuse, disagreeable pain
commencing shortly thereafter

11. • Pain typically is perceived initially as a brief, sharp, prickling
sensation that is easily localized; this is fast pain originating
from specific mechanical or heat nociceptors
• This feeling is followed by a dull, aching, poorly localized
sensation that persists for a longer time and is more
unpleasant; this is slow pain triggered by chemicals, especially
bradykinin (a normally inactive substance that is activated by
enzymes released into the ECF from damaged tissue)

12. • Bradykinin and related compounds not only provoke pain by
stimulating the polymodal nociceptors, but they also contribute
to the inflammatory response to tissue injury
• This slow, aching pain is activated for a prolonged time because
of the persistence of released chemicals at the site long after
removal of the mechanical or thermal stimulus that caused the
tissue damage

13. CAPSAICIN AS AN ANALGESIC.!
• Interestingly, the peripheral receptors of afferent C fibers are
activated by capsaicin, (the ingredient in hot chili peppers that gives
them their fiery zing)
• In addition to binding with pain receptors, capsaicin binds with heat
receptors hence the burning sensation when eating hot peppers
• Ironically, local application of capsaicin can reduce clinical pain,
most likely by over stimulating and damaging the nociceptors with
which it binds

15. HIGHER-LEVEL PROCESSING OF PAIN INPUT
Multiple structures are involved in pain processing i.e.
• Primary afferent pain fibers
• Ascending pain pathways in the spinal cord, and
• Brain regions involved with pain perception

16. • The primary afferent pain fibers synapse with specific second-order
excitatory interneurons in the dorsal horn of the spinal cord
• In response to stimulus-induced action potentials, afferent pain
fibers release neurotransmitters that influence these next neurons in
line
• The two best known of these pain neurotransmitters are:
– Substance P
– Glutamate

17. SUBSTANCE P
• It is unique to pain fibers
• Activates ascending pathways that transmit nociceptive
signals to higher levels for further processing

18. • Ascending pain pathways have different destinations in the
cortex, the thalamus, and the reticular formation
• Cortical somatosensory processing areas localize the pain,
whereas other cortical areas participate in other conscious
components of the pain experience, such as deliberation
about the incident

19. Pain can still be perceived in the absence of the cortex presumably at
the level of the thalamus
The reticular formation increases the level of alertness associated
with the noxious encounter
Interconnections from the thalamus and reticular formation to the
hypothalamus and limbic system elicit the behavioral and emotional
responses accompanying the painful experience
The limbic system is especially important in perceiving the unpleasant
aspects of pain

21. GLUTAMATE
• Glutamate, the other neurotransmitter released from primary
afferent pain terminals, is a major excitatory neurotransmitter
• Glutamate acts on two different plasma membrane receptors on
the dorsal horn excitatory interneurons, with two different
outcomes

22. • First, binding of glutamate with its AMPA receptors leads to
permeability changes that ultimately result in the generation
of action potentials in the dorsal horn cells
• These action potentials transmit the pain message to higher
centers

23. • Second, binding of glutamate with its NMDA receptors leads to Ca2+
entry into these neurons
– This pathway is not involved in the transmission of pain
messages. Instead,
• Ca2+ initiates second-messenger systems that make the dorsal
horn cells more excitable than usual

24. • This hyperexcitability contributes in part to the
exaggerated sensitivity of an injured area to
subsequent exposure to painful or even normally
nonpainful stimuli, such as a light touch

25. Think about how exquisitely sensitive your
sunburned skin was, even to clothing

26. • Other mechanisms also contribute to supersensitivity of an injured
area. For example, responsiveness of the pain-sensing peripheral
receptors can be boosted so that they react more vigorously to
subsequent stimuli
• This exaggerated sensitivity serves a useful purpose by discouraging
activities that could cause further damage or interfere with healing
of the injured area
• Usually this hypersensitivity resolves as the injury heals

27. ABNORMAL PERSISTENT CHRONIC PAIN
• Persistent, chronic pain, sometimes excruciating, can occur in
the absence of tissue injury.
• This results from prolonged hypersensitivity within the pain
transmission pathways in the peripheral nerves or in the CNS

28. ABNORMAL PERSISTENT CHRONIC PAIN
• The persistent, abnormal excitability among neurons in the pain
pathways that leads to chronic pain is the result of a complex
interplay among the involved neurons, glial cells (especially
microglia and astrocytes), and immune cells
• These cells release many types of intercellular chemical messengers
that are meant to be helpful, such as by increasing synaptic strength
or by promoting healing in response to an original tissue insult

29. ABNORMAL PERSISTENT CHRONIC PAIN
• However, many of these molecules increase the excitability of
involved neurons
• The overly sensitive neurons continue to fire and transmit pain
signals in what appears to be spontaneously in the absence of
obvious tissue damage
• Chronic pain is sometimes categorized as neuropathic pain
• Worldwide, 15% to 20% of adults suffer from this affliction

30. BUILT-IN ANALGESIC SYSTEM

31. • CNS contains a built-in pain-suppressing or analgesic system that
suppresses transmission in the pain pathways as they enter the spinal
cord
• Three brain-stem regions are part of this descending analgesic pathway:
– The periaqueductal gray matter
– Specific nuclei in the medulla
– Reticular formation
• Electrical stimulation of any of these parts of the brain produces profound
analgesia

32. Endogenous opiates are:
Endorphins , enkephalins, and dynorphin
Morphine binds to these same
opiate receptors

33. Injection of morphine into the periaqueductal gray matter and
medulla causes profound analgesia, suggesting that endogenous
opiates also are released centrally to block pain

34. Factors known to modulate pain include exercise, stress,
and acupuncture

35. ACUPUNCTURE
• Acupuncture analgesia (AA), the technique of relieving pain
by inserting and manipulating threadlike needles at key
points
• This has been practiced in China for more than 2000 years but
is relatively new to Western medicine and still remains
controversial in the United States

36. ACUPUNCTURE
• The overwhelming body of evidence supports the
acupuncture endorphin hypothesis as the primary
mechanism of AA’s action
• According to this hypothesis, acupuncture needles activate
specific afferent nerve fibers, which send impulses to the
CNS

37. ACUPUNCTURE
• Here, the incoming impulses cause analgesia by blocking
pain transmission at both the spinal-cord and the brain level
through use of endorphins and closely related endogenous
opiates
• Several other neurotransmitters, such as serotonin and
norepinephrine, as well as cortisol are implicated as well

38. HEADACHE

39. HEADACHE
• https://my.clevelandclinic.org/health/diseases/9639-
headaches-in-adults

40. REFRENCE
Lauralee Sherwood, (2013). Human physiology: from cells to
systems. Belmont, California: Brooks/Cole, Cengage Learning.