Physiology of pain
Prof. Vajira Weerasinghe
Professor of Physiology, Faculty of Medicine
University of Peradeniya & Consul...
Topics covered in the lecture
1.

What is pain (International definition of pain)

2.

Dual nature of pain: fast pain and ...
What is pain?
• Pain is a difficult word to define
• Patients use different words to
describe pain
• eg.
•

Aching, Pins a...
What is pain?
• There is an International definition of pain
formulated by the IASP (International
Association for the stu...
definition of pain
• It is a symptom
• Associated signs are crying, sweating,
increased heart rate, blood pressure,
behavi...
Different situations
•No stimuli, but pain is felt
•phantom limb pain
•eg. in amputated limb
•Stimuli present, but no pain...
Pain terminology
International Association for the Study of Pain 2011
•
•
•
•
•

•
•

•

•

Paresthesia
– An abnormal sens...
Pain terminology
International Association for the Study of Pain 2011
• Neuropathic Pain
– Pain caused by a lesion or dise...
• Nociceptive pain
• Neuropathic pain
• Psychogenic pain
• Transduction
– Process of converting noxious stimulus to action
potentials

• Perception
– Central processing of nocicep...
Dual nature of pain
fast and slow pain
• fast pain
–
–
–
–
–
–
–

acute
pricking type
well localised
short duration
Aδ fib...
• Physical

Stimuli

– pressure etc

• Electrical
• Thermal
– cold, hot

• Chemical
– H+, lactic acid, K+, histamine, brad...
receptors
•

there are no specialised receptors

•

free nerve endings are sensitive to pain stimuli

•

free nerve ending...
central connections
• afferent fibre enters the spinal cord
• synapses in laminae I and II (substantia gelatinosa)
• visce...
ascending pathway
• crosses the midline
• ascends up as the lateral spinothalamic tract
• pain originating from head and n...
n
se
r
so
te
or
yc

thalamocortical
tracts

x

thalamus

lateral
spinothalamic
tract
C fibre
Pain perception
• This occurs at different levels
– thalamus is an important centre of
pain perception
• lesions of thalam...
Pathophysiology of pain
• Pain sensations could arise due to
– Inflammation of the nerves (neuritis)
– Injury to the nerve...
Descending pain modulatory system
• several lines of experimental
evidence show the presence of
descending pain modulatory...
opioid peptides
• short peptides originally known to be secreted
in CNS and later found to be present in GIT etc
∀ β endorphin

opioid peptides

• Earliest to discover, present in pituitary

• encephalins - met & leu
• widely distribut...
• descending tracts involving opioid peptides as
neurotransmitter were discovered
• these were known to modify (inhibit) p...
• first tract was discovered in 1981 by Fields and
Basbaum
– it involves enkephalin secreting neurons in the
reticular for...
periaqueductal
grey nucleus

midbrain

pons
nucleus raphe
magnus

medulla

spinal cord

substantia gelatinosa
• in the subtantia gelatinosa
– enkephalin secreting neuron is involved in
presynaptic inhibition of the pain impulse
tran...
substantia
gelatinosa

descending inhibitory tract
dorsal horn

c fibre input

substantia
gelatinosa cell
Presynaptic inhibition

enkephalin

substance P
Presynaptic inhibition

enkephalin
substance P
blocking of
pain impulse

pain impulse
• since then various other descending tracts were discovered
• all of them share following common features
– involved in b...
• final pain perception depends on activity of the
– ascending pain impulse transmitting tracts
– descending pain modulato...
n
se
r
so
x
te
or
yc

thalamocortical
tracts

thalamus

lateral
spinothalamic
tract
C fibre
Theories
of pain

Intensity theory

touch
pain

There is a single pathway for touch
and pain
Less intensity produces touch...
Gate control theory
• This explains how pain can be relieved very quickly by
a neural mechanism
• First described by P.D. ...
Gate control theory
central control

touch
Aβ fibre

pain
C & Aδ
fibres

transmission
cell
Gate control theory
pain is felt
central control

touch
Aβ fibre

pain
C & Aδ
fibres

transmission
cell

+
gate is
opened
...
Gate control theory
central control

touch
Aβ fibre

+
pain
C & Aδ
fibres

-

pain is
not felt

transmission
cell

gate is...
Gate control theory
• This theory provided basis for
various methods of pain relief
– Massaging a painful area
– Applying ...
Gate control theory
• But the anatomcal basis for all the connections
of Wall’s original diagram is lacking

?
?
WDR (wide dynamic range cells)
• It is known that some of the second order
neurons of the pain pathway behave as
wide dyna...
WDR (wide dynamic range cells)
pain &
mech

C fibre

mech

A fibre

excitatory

WDR cell

inhibitory
WDR cells
• have been found in
– Spinal cord
– Trigeminal nucleus
– Brain stem
– Thalamus
– Cortex
Modifications to the gate control theory
• this could be modified in the
light of enkephalin activity
and WDR cells
• inhi...
referred pain
• sometimes pain arising from viscera are not felt
at the site of origin but referred to a distant site.
– e...
referred pain - theories
• convergence theory
– somatic & visceral structures
converge on the same
dermatome
– generally i...
referred pain - theories
• facilitatory theory
– somatic & visceral structures
converge on the same
dermatome
– stimulatio...
• hypoxia / pressure / inflating a BP cuff
– first affect large A fibres (touch & pressure sense)
– then affect Aδ fibres ...
Pain arising from abdominal
viscera
•

Mediated by C fibres

•

Mainly due to the sensations of distention, muscular contr...
Capsaicin and vanniloid receptors
•

Active compound in chilies is capsaicin

•

Capsaicin chemically is one of the vanill...
Cannabinoid receptor
• Cannabis (marijuvana or ganja) causes pain relief
• Cannabis act on cannabinoid receptors found in ...
Neurotransmitters in the CNS
• Excitatory
– Substance P
– Glutamate (NMDA receptor)
– Neurokinin A and B
– calcitonin gene...
Neurotransmitters in the CNS
• Inhibitory
– GABA
– Noradrenalin
– Serotonin
– Enkephalins
Glutamate
•
•
•
•

•
•
•

The NMDA receptor mediates a host of spinal responses to severe painful
stimulation
Normally, th...
GABA
•
•
•
•

GABA is widespread in the brain and spinal cord
inhibitory effects
Interneurones in laminae I, II and III ar...
c-fos gene and FOS protein
• Discovery of gene c-fos (a viral oncogene) & its
cellular product, the protein called Fos see...
Pain memory
•

Memory of pain can be more damaging than its initial experience

•

Central sensitization
– Increased respo...
Psych c pain 2013
Psych c pain 2013
Upcoming SlideShare
Loading in...5
×

Psych c pain 2013

794

Published on

0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
794
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
49
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

Psych c pain 2013

  1. 1. Physiology of pain Prof. Vajira Weerasinghe Professor of Physiology, Faculty of Medicine University of Peradeniya & Consultant Neurophysiologist, Teaching Hospital, Peradeniya www.slideshare.net/vajira54
  2. 2. Topics covered in the lecture 1. What is pain (International definition of pain) 2. Dual nature of pain: fast pain and slow pain 3. What causes pain : pain stimuli 4. Nerve pathways carrying pain signals to the brain 5. Brain areas involved in pain perception 6. Pain modulatory pathways 7. Neurochemicals involved in pain pathways
  3. 3. What is pain? • Pain is a difficult word to define • Patients use different words to describe pain • eg. • Aching, Pins and needles, Annoying, Pricking, Biting, Hurting, Radiating, Blunt, Intermittent, Burning, Sore, Miserable, Splitting, Cutting, Nagging, Stabbing, Crawling, Stinging, Crushing, Tender, Dragging, Numbness, Throbbing, Dull, Overwhelming, Tingling, Electric-shock like, Penetrating, Tiring, Excruciating, Piercing, Unbearable • Different words in Sinhala or in Tamil
  4. 4. What is pain? • There is an International definition of pain formulated by the IASP (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 IASP – International Association for the Study of Pain 2011
  5. 5. definition of pain • It is a symptom • Associated signs are crying, sweating, increased heart rate, blood pressure, behavioural changes • It is difficult to describe pain although we know what it is • It is difficult to measure pain – visual analogue scale is used • It is a complex sensory modality essential for survival
  6. 6. Different situations •No stimuli, but pain is felt •phantom limb pain •eg. in amputated limb •Stimuli present, but no pain felt •eg. soldier in battle field, sportsman in arena •Pain due to a stimulus that does not normally provoke pain •Allodynia •Pain caused by a lesion or disease of the somatosensory nervous system •Neuropathic pain
  7. 7. Pain terminology International Association for the Study of Pain 2011 • • • • • • • • • Paresthesia – An abnormal sensation, whether spontaneous or evoked Dysesthesia – An unpleasant abnormal sensation, whether spontaneous or evoked Hyperalgesia – Increased pain from a stimulus that normally provokes pain Allodynia – Pain due to a stimulus that does not normally provoke pain Hyperesthesia – Increased sensitivity to stimulation, excluding the special senses (increased cutaneous sensibility to thermal sensation without pain ) Hyperalgesia – Increased pain from a stimulus that normally provokes pain Causalgia – A syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes Hyperpathia – a painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold Neuralgia – Pain in the distribution of a nerve or nerves
  8. 8. Pain terminology International Association for the Study of Pain 2011 • Neuropathic Pain – Pain caused by a lesion or disease of the somatosensory nervous system • Nociceptive pain – Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors • Neuropathy – A disturbance of function or pathological change in a nerve: in one nerve, mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse and bilateral, polyneuropathy • Nociception – The neural process of encoding noxious stimuli • Noxious stimulus – A stimulus that is damaging or threatens damage to normal tissues. • Pain threshold – The minimum intensity of a stimulus that is perceived as painful.
  9. 9. • Nociceptive pain • Neuropathic pain • Psychogenic pain
  10. 10. • Transduction – Process of converting noxious stimulus to action potentials • Perception – Central processing of nociceptive impulses in order to interpret pain
  11. 11. Dual nature of pain fast and slow pain • fast pain – – – – – – – acute pricking type well localised short duration Aδ fibres are involved fast conduction 20 m/s somatic pain • slow pain – – – – – chronic throbbing type poorly localised long duration unmyelinated C fibres are involved – slow conduction 1-2 m/s – visceral pain
  12. 12. • Physical Stimuli – pressure etc • Electrical • Thermal – cold, hot • Chemical – H+, lactic acid, K+, histamine, bradykinin, acetylcholine, proteolytic enzymes – Prostaglandins • these increase the sensitivity (decrease the threshold) for other nociceptive stimuli
  13. 13. receptors • there are no specialised receptors • free nerve endings are sensitive to pain stimuli • free nerve endings are distributed everywhere • both somatic and visceral tissues • except brain tissue and lung parenchyma • nociceptors are very slowly adapting type • different types of nociceptors – some respond to one stimulus – some respond to many stimuli (polymodal) – some may not respond to the standard stimuli (silent nociceptors), they respond only when inflammatory substances are present • TRPV1 receptor (capsaicin receptor) – respond to capsaicin, heat, low pH – stimulation leads to painful, burning sensation
  14. 14. central connections • afferent fibre enters the spinal cord • synapses in laminae I and II (substantia gelatinosa) • visceral fibres have more diffused distribution (I,V,X) – (Large Ab fibres termiate in laminae layers III to V) substantia gelatinosa Neurotransmitter at the first synapse of the pain pathway is substance P
  15. 15. ascending pathway • crosses the midline • ascends up as the lateral spinothalamic tract • pain originating from head and neck region travel through trigeminal nerve, trigeminal nucleus and supply thalamus • spontaneous firing of trigeminal pathway may result in “trigeminal neuralgia” Pain C fibre substantia gelatinosa lateral spinothalamic tract
  16. 16. n se r so te or yc thalamocortical tracts x thalamus lateral spinothalamic tract C fibre
  17. 17. Pain perception • This occurs at different levels – thalamus is an important centre of pain perception • lesions of thalamus produces severe type of pain known as ‘thalamic pain’ – Sensory cortex is necessary for the localisation of pain – Other areas are also important • reticular formation, limbic areas, hypothalamus and other subcortical areas
  18. 18. Pathophysiology of pain • Pain sensations could arise due to – Inflammation of the nerves (neuritis) – Injury to the nerves and nerve endings with scar formation (disk prolapse) – Injury to the structures in the spinal cord, thalamus or cortical areas that process pain information (spinal trauma) – Abnormal activity in the nerve circuits that is perceived as pain (phantom limb pain) – Nerve invasion, for example by cancer (brachial plexopathy)
  19. 19. Descending pain modulatory system • several lines of experimental evidence show the presence of descending pain modulatory system – discovery of morphine receptors – they were known to be present in the brain stem areas – discovery of endogenous opioid peptides • eg. Endorphines, enkephalins, dynorphin
  20. 20. opioid peptides • short peptides originally known to be secreted in CNS and later found to be present in GIT etc
  21. 21. ∀ β endorphin opioid peptides • Earliest to discover, present in pituitary • encephalins - met & leu • widely distributed • dynorphin • Endomorphine 1 & 2 • Pronociceptins Naloxone is an opioid antagonist. It blocks the actions of opioid Receptors: mu, kappa, delta, recently discovered ORL1 receptor
  22. 22. • descending tracts involving opioid peptides as neurotransmitter were discovered • these were known to modify (inhibit) pain impulse transmission at the first synapse at the substantia gelatinosa
  23. 23. • first tract was discovered in 1981 by Fields and Basbaum – it involves enkephalin secreting neurons in the reticular formation – starting from the PAG (periaqueductal grey area) of the midbrain – ending in the NRM (nucleus raphe magnus) of the medulla – from their ending in the substantia gelatinosa of the dorsal horn
  24. 24. periaqueductal grey nucleus midbrain pons nucleus raphe magnus medulla spinal cord substantia gelatinosa
  25. 25. • in the subtantia gelatinosa – enkephalin secreting neuron is involved in presynaptic inhibition of the pain impulse transmission by blocking substance P release
  26. 26. substantia gelatinosa descending inhibitory tract dorsal horn c fibre input substantia gelatinosa cell
  27. 27. Presynaptic inhibition enkephalin substance P
  28. 28. Presynaptic inhibition enkephalin substance P blocking of pain impulse pain impulse
  29. 29. • since then various other descending tracts were discovered • all of them share following common features – involved in brain stem reticular areas – enkephalins act as neurotransmitters at least in some synapses – most of these tracts are inhibitory – midbrain nuclei are receiving inputs from various areas in the cortex, subcortical areas, limbic system, hypothalamus etc – the ascending tract gives feedback input to the descending tracts – recently even nonopioid peptides are known to be involved
  30. 30. • final pain perception depends on activity of the – ascending pain impulse transmitting tracts – descending pain modulatory (inhibitory) tracts
  31. 31. n se r so x te or yc thalamocortical tracts thalamus lateral spinothalamic tract C fibre
  32. 32. Theories of pain Intensity theory touch pain There is a single pathway for touch and pain Less intensity produces touch Increased intensity produces pain Specificity theory touch pain There are two different pathways for touch and pain
  33. 33. Gate control theory • This explains how pain can be relieved very quickly by a neural mechanism • First described by P.D. Wall & Melzack (1965) • “There is an interaction between pain fibres and touch fibre input at the spinal cord level in the form of a ‘gating mechanism’
  34. 34. Gate control theory central control touch Aβ fibre pain C & Aδ fibres transmission cell
  35. 35. Gate control theory pain is felt central control touch Aβ fibre pain C & Aδ fibres transmission cell + gate is opened when C fibre is stimulated, gate will be opened & pain is felt
  36. 36. Gate control theory central control touch Aβ fibre + pain C & Aδ fibres - pain is not felt transmission cell gate is closed when Aβ & C fibres are stimulated together, gate will be closed & pain is not felt
  37. 37. Gate control theory • This theory provided 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 ?
  38. 38. Gate control theory • But the anatomcal basis for all the connections of Wall’s original diagram is lacking ? ?
  39. 39. WDR (wide dynamic range cells) • It is known that some of the second order neurons of the pain pathway behave as wide dynamic range neurons • they can be stimulated by pain stimuli but inhibited by touch stimuli
  40. 40. WDR (wide dynamic range cells) pain & mech C fibre mech A fibre excitatory WDR cell inhibitory
  41. 41. WDR cells • have been found in – Spinal cord – Trigeminal nucleus – Brain stem – Thalamus – Cortex
  42. 42. Modifications to the gate control theory • this could be modified in the light of enkephalin activity and WDR cells • inhibitory interneuron may be substantia gelatinosa cell • descending control is more important • WDR cells may represent neurons having pain as well as touch input
  43. 43. referred pain • sometimes pain arising from viscera are not felt at the site of origin but referred to a distant site. – eg. • cardiac pain referred to the left arm • diaphargmatic pain referred to the shoulder – this paradoxical situation is due to an apparent error in localisation
  44. 44. referred pain - theories • convergence theory – somatic & visceral structures converge on the same dermatome – generally impulses through visceral pathway is rare – centrally brain is programmed to receive impulses through somatic tract only – therefore even if the visceral structure is stimulated brain misinterpret as if impulses are coming from the somatic structure somatic + ++ ++ + second order neuron + visceral
  45. 45. referred pain - theories • facilitatory theory – somatic & visceral structures converge on the same dermatome – stimulation of visceral structure facilitates transmission through somatic tract somatic + ++ ++ + second order neuron + visceral
  46. 46. • hypoxia / pressure / inflating a BP cuff – first affect large A fibres (touch & pressure sense) – then affect Aδ fibres (temperature sense & pricking pain) – lastly C fibres (burning pain) • local anaesthetics – first relieve burning pain ( C fibres) – then temperature sense & pricking pain (Aδ fibres) – lastly touch& pressure sensation (large A fibres)
  47. 47. Pain arising from abdominal viscera • Mediated by C fibres • Mainly due to the sensations of distention, muscular contraction, inflammation, hypoxia but not to cutting, tearing, local irritation, burning • Typically vague, dull, and nauseating • These structures are innervated by autonomic nerve fibers • It is poorly localized and tends to be referred to areas corresponding to the embryonic origin of the affected structure – – – stomach, duodenum, liver and pancreas referred to upper abdomen small intestines, proximal colon and appendix referred to periumbilical pain distal colon and GU tract referred to lower abdominal pain • Peritonitis causes somatic pain • Diffuse localization of true visceral pain is probably due to the low density of visceral sensory innervation and extensive divergence of the visceral input within the central nervous system
  48. 48. Capsaicin and vanniloid receptors • Active compound in chilies is capsaicin • Capsaicin chemically is one of the vanilloids • Capsaicin receptor is called TRPV1 – • (Transient receptor potential vanilloid type 1) This receptor is also stimulated by – heat greater than 43°C – low pH • This receptor is sensitised by prostaglandins and bradykinins • Upon prolonged exposure to capsaicin TRPV1 activity decreases – this phenomenon is called desensitization – Extracellular calcium ions are required for this phenomenon – This causes the paradoxical analgesic effect of capsaicin
  49. 49. Cannabinoid receptor • Cannabis (marijuvana or ganja) causes pain relief • Cannabis act on cannabinoid receptors found in pain pathway • There are endocannabinoids as well • Cannabinoid receptor-related processes are involved in cognition, memory, anxiety, control of appetite, emesis, motor behavior, sensory, autonomic and neuroendocrine responses, immune responses and inflammatory effects
  50. 50. Neurotransmitters in the CNS • Excitatory – Substance P – Glutamate (NMDA receptor) – Neurokinin A and B – calcitonin gene-related peptide – vasoactive intestinal polypeptide – Somatostatin – bombesin
  51. 51. Neurotransmitters in the CNS • Inhibitory – GABA – Noradrenalin – Serotonin – Enkephalins
  52. 52. Glutamate • • • • • • • The NMDA receptor mediates a host of spinal responses to severe painful stimulation Normally, the receptor is inactive as it is blocked by a Mg ion C fibre stimulation removes this Mg ion and activates the receptor there is a dramatic and long-lasting central response, with some populations of spinal neurones becoming more and more sensitive to stimulation Activation causes production of c-fos & spinal production of prostanoids and nitric oxide drugs that antagonise the effect of glutamate at the NMDA receptor tend to induce side effects in higher functions too but the combination of low dose NMDA antagonists with opioids may be supra-additive with fewer side effects.
  53. 53. GABA • • • • GABA is widespread in the brain and spinal cord inhibitory effects Interneurones in laminae I, II and III are GABA-rich mediate gate control in the dorsal horn by synapsing on neurones that contain substance P
  54. 54. c-fos gene and FOS protein • Discovery of gene c-fos (a viral oncogene) & its cellular product, the protein called Fos seem crucial to the profound central nervous system changes that occur when an animal (or man) feels pain • CNS c-fos expression correlates extremely well with painful stimulation • We now have a molecular marker for pain!
  55. 55. Pain memory • Memory of pain can be more damaging than its initial experience • Central sensitization – Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input • Peripheral sensitization – Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields • Clinical interventions to blunt both the experience and persistence of pain or to lessen its memory are now applied • Preemptive analgesia – Pre-emptive analgesia is a treatment that is initiated before the surgical procedure in order to reduce sensitization – Many studies have demonstrated that analgesic intervention before a noxious stimulus or injury is more effective at averting central sensitization than the same analgesic intervention given after the stimulus
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×