1. UNDERSTANDING OF PAIN “ Nociceptive, Neuropathic & Mixed Pain ”
Nur Surya Wirawan
Department of Anesthesiology,
Intensive Care and Pain Management
Faculty of Medicine
University of Hasanuddin
Makassar

2. Objective After this lecture, participants are able to understand :
Definition of Pain
Mechanism of Pain perception
Nociceptive Pain
Neuropathic Pain
Mixed Pain
Chronic Pain
Take Home Messange

3. Before Eve was created from Adam's Rib, Adam was put into sleep

4. Pain was faithfully transmitted from periphery to brain
Descartes (17th Century)
First ideas….
Pain was faithfully transmitted
from periphery to brain
A pure stimulus response relationship

5. MELZACK and WALL ‘Gate Control Theory’
Progress in understanding pain
MELZACK and WALL ‘Gate Control Theory’
1965-

7. Introduce Hypothesis of
1965 MELZACK and WALL
Introduce Hypothesis of
“GATE CONTROL THEORY”
Brain
GATE CONTROL SYSTEM Aβ - + +
DHN
ACTION
SYSTEM SG - - + C
The beginning of “MODULATION”

9. Definition of Pain
Scientific : Pain is unpleasant sensory and emotional experience ascociated with actual or potential tissue damage or describe in term of such damage. (Merskey ,accepted by IASP 1979)
Clinical : “Pain is whatever the experiencing person says. (Mc Caffery 1997)
“Pain is what ever the pateint says” 9

10. From this definition, some conclusions can be obtained;
PHYSIOLOGICAL PAIN, is a normal sensation, elicited by potential tissue damage  Withdrawal reflex
PATHOPHYSIOLOGICAL PAIN, is an abnormal sensation :
Due to actual tissue damage  inflamed pain = clinical pain = acute pain e.g. : postoperative pain
Due to nervous system damage  neuropathic pain
PATHOLOGICAL PAIN,
Described in intern of such damage  CHRONIC PAIN
Chronic pain is now consider as “a disease of entity”. Causing suffering, reducing QOL

11. KLASIFIKASI NYERI Menurut waktu  Nyeri akut & kronik N Y E R I
Menurut patofisiologinya :
Nyeri fisiologik
Nyeri klinis ( nyeri patofisiologik)
Nyeri nosiseptif
Nyeri neuropatik
Perifer
Sentral
3. Nyeri psikogenik / idiopatik

12. Acute Pain
Acute Pain is the normal predicted physiological response to an adverse chemical, thermal or mechanical stimulus …., associated with surgery, trauma and acute illness.”“
( Federation of State Medical Boards of US )

13. Acute pain Acute onset, localized, sharp and high intensity pain.
(Pain of recent onset and probable limited duration, IASP)
Acute onset, localized, sharp and high intensity pain.
Usually self limiting.
Signs of physiologic response of various organs or systems, e.g. sweating, palpitation and increased of blood pressure.
Identifiable causes or related to injury or diseases
Nyeri muskuloskeletal akut memiliki ciri-ciri, yaitu:
Awitan tiba-tiba, dan umumnya terlokalisir pada lokasi yang mengalami patologi.
Seringkali disertai dengan manifestasi klinis lain seperti ganggunan pada sistim organ tertentu misalnya takikardia pada sistim kardiovaskular.
Terpenting dari nyeri ini adalah: nyeri akan menghilang seiring dengan menyembuhnya jejas.

14. Causes of acute pain Trauma Surgery Delivery
Invasive medical procedures
Acute illness.
Penyebab nyeri akut umumnya dapat ditentukan dengan jelas seperti nyeri akibat pembedahan, trauma fisik, persalinan, prosedur medik yang invasif seperti kateterisasi jantung atau penyakit inflamasi akut seperti radang tenggorokan.

15. Acute Pain Somatic pain Visceral pain constant constant sharp aching
well localized
constant
dull aching
poorly localized
usually with nausea and vomit
occasional colicky or cramp
often referred to cutaneous sites

16. Referred Pain
Figure 10-13: Referred pain

17. There are two sensory afferent neurons
Large myelinated A fibers, very fast conduction velocity. Respond to innocuous stimuli
Small myelinated A & C unmyelinated fibers, have slow conduction velocity. Respond to noxious stimuli
Large
fibers A
Dorsal root
ganglion
Dorsal Horn A
Small
fibers C
Peripheral sensory
Nerve fibers

18. Physiological Pain A C fiber A Touch Tactile Pressure
NOXIOUS STIMULUS
INNOCUOUS STIMULUS A
C fiber A
DHN
DHN
PAIN
INNOCUOUS SENSATION
Touch
Tactile
Pressure
First Pain
Second Pain

19. Responds to noxious stimuli
Pain Afferent neurons
A myelinated fiber
C unmyelinated fiber
Responds to noxious stimuli
Both have
free nerve endings
Naciceptors
(receptor Nyeri) 19

20. Nociceptors Mechanothermal nociceptors Polimodal nociceptors
Respond to mechanical and thermal stimuli.
display rapid conduction.
Produced first pain and well localized.
Ad fibers respond to this naciceptors.
Polimodal nociceptors
Respond to mechanical, thermal and chemical.
Slow conduction.
Produced second pain and diffuse.
C fibers respond to this receptor.
Exist in many tissues, skin, muscle, pariosteum, joints, and viscera, except brain.

21. 1. Transduction 2. Transmission 3. Modulation 4. Perception
NOCICEPTION
Between noxious stimulus and perception of pain lies a complex series of electrophysioloc event, collectively termed NOCICEPTION 4 physiologic processes are involved:
1. Transduction
2. Transmission
3. Modulation
4. Perception

22. TRANSDUCTION
TRANSDUCTION
Process whereby noxious stimuli are translated into electrical activity at the sensory endings of nerve
Pressure
Heat
Chemical

23. Transduction Process 1. Transduction 3. Propagation
Ca2+ K+ K+
Na+
1. Transduction
3. Propagation
2. Spike Initiation
4. Transmitter Release
Modified Meliala, 2006

24. NOCICEPTIVE PAIN Noxious Peripheral Stimuli Pain Heat
Autonomic Response
Withdrawal Reflex
Heat
Cold
Brain
Intense
Mechanical
Nociceptor sensory neuron
Force
Heat
Spinal cord
Cold
Modification Meliala, 2005

25. TRANSMISSION
Propagation of impulses throughout the sensory nervous system. Or
Passage of signal from periphery to the central NS.

26. Afferent Synaptic in DHN
Substantia
gelatinosa
Marginal layer A
Medial A C
Lateral
Nucleus
proprius

27. Medula Spinalis
Dahulu : dikenal sebagai “SIMPLE RELAY STATION” Untuk transmisi Nyeri Sekarang : Sebagai tempat interaksi yang kompleks antara
Serabut-serabut Eksitatori
Serabut-serabut inhibitori
MODULASI NYERI

28. Serabut Eksitatori & Inhibitori
Glutamate
(Subs P) C Ab Ad
Glutamate +
Glutamate
OTAK
WDR & NS -
Serabut
Inhibitori
GABA
Glycine
Opioids
NA, 5HT

29. MODULATION
The process whereby endogenous analgesic system (opioid, serotonergic, and noradrenergic) can modify nociceptive transmission

30. Spinal Cord SPINAL CORD (DHN) is the key point of modulation
The place where afferent input is processed.
Where interaction between excitatory and inhibitory system.
NOCICEPTION IS BORN IN DORSAL HORN, BUT WE DON’T CALL IT PAIN TILL IT REACHES THE BRAIN (Dr. Ken Casey)

31. Modulation

32. Descending Modulating Pathways
Ascending pathways is modulated by descending
modulating pathways in several higher centers;
CEREBRAL CORTEX
THALAMUS
MIDBRAIN/ BRAINSTEM
Periaqueductal gray (PAG)
Nuclei raphe magnus (NRM)
Locus ceruleus (LC)
Sub ceruleus
SPINAL CORD

33. SEROTONIN
NEOREPINEPHRINE

34. Two Kind of Stimuli Modulation Noxious/ Innocuous
Nociceptor
Noxious/ Innocuous
Modulation
DHN
Facilitatory/ excitatory
Inhibitory
Pain
No Pain
Pain stimulus is not perfect terminology

35. Pain
CNS
Inhibition
Excitation
Nociception

36. X Nociception Without Pain Pain CNS Nociception Inhibition Excitation
Example: Stress Induced Analgesia
Nociception

37. X Pain Without Nociception Pain CNS Nociception Inhibition Excitation
Example: Phantom ,neurophatic pain
Nociception

38. Pain Perception Excitatory system Inhibitory system
Depends on the balance between:
Excitatory system
Inhibitory system
(Cognitive, emotional, behavior)

41. Pain perception depend on the meaning of injury
Beecher
Pain perception depend on the meaning of injury

42. Pain Perception Perception Medulation transmission Transduction Pain
Descending
modulation
Dorsal Horn
transmission
Ascending
input
Dorsal root ganglion
Transduction
Spinothalamic
tract
Peripheral
nerve
Trauma
Peripheral
nociceptors
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.

43. Perception Perception
Final process to create the final subjective and emotional experience that we call pain
Perception
Pain
Perception
Brain
How pain perception is processed, no body knows and
Where pain perceptions in the brain still unclear.

44. What is nociceptive pain?
A sensory experience that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli
Painful region is typically localized at the site of injury – often described as throbbing, aching or stiffness
Usually time-limited and resolves when damaged tissue heals (e.g. bone fractures, burns and bruises)
Note to speaker: this slide contains an animated build. The first bullet appears automatically, then click on the slide to bring up the remaining 4 bullets sequentially.
The painful region is typically localized at the site of injury in nociceptive pain. This contrasts with neuropathic pain where the painful region may not necessarily be the same as the site of injury and occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain). This is outlined on slide 15.
Nociceptive pain usually responds well to conventional analgesics such as acetaminophen (paracetamol), non-steroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase (COX)-2 inhibitors or opioids.
Can also be chronic (e.g. osteoarthritis)
Responds to conventional analgesics

45. NOCICEPTIVE PAIN Noxious Peripheral Stimuli Pain Heat
Autonomic Response
Withdrawal Reflex
Heat
Cold
Brain
Intense
Mechanical
Nociceptor sensory neuron
Force
Heat
Spinal cord
Cold
Modification Meliala, 2005

46. NSAID (Cox1 or Cox2) Prostaglandins Bradykinin Leukotriens PAIN
TISSUE INJURY
Prostaglandins
Bradykinin
Leukotriens
PAIN
Histamine
NSAID
(Cox1 or Cox2)

47. Pain-sensitive tissue
Inflammation Tissue 1
Pain-sensitive tissue
Painful stimulus
Prostaglandin
Substance P
Histamine
Mast cell
Blood vessel
Bradykinin
Nociceptor 2 3 1
Prostaglandins produced in response to tissue injury; increase sensitivity of nociceptor (pain) 2
Nociceptor then releases substance P, which dilates blood vessels and increases release of inflammatory mediators, such as Bradykinin (redness & heat) 3
Substance P also promotes degranulation of mast cells, which release histamine (swelling) 47

48. Sensitization 10 8 6 Hyperalgesia Normal Pain Response 4 2 Injury
Hyperalgesia
Normal
Pain
Response
Injury
Allodynia
Pain Intensity
Hyperalgesia—heightened sense of pain to noxious stimuli
Allodynia—pain resulting from normally painless stimuli
Stimulus Intensity
Gottschalk A et al. Am Fam Physician. 2001;63:

49. (INFLAMATION PAIN) Ab Fiber Ad Fiber Hyperexitable DHN CLINICAL PAIN
Low Intensity Stimulus
Ab Fiber
Ad Fiber
PNS
CNS
Hyperexitable DHN
DHN
PAIN

50. What is neuropathic pain?
Pain caused by a primary lesion or dysfunction in the peripheral or central nervous system
Pain often described as shooting, electric shock- like or burning.
The painful region may not necessarily be the same as the site of injury.
Note to speaker: this slide contains an animated build. The first bullet appears automatically, then click on the slide to bring up the remaining 4 bullets sequentially.
The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain).
In peripheral neuropathic pain, it is in the territory of the affected nerve or nerve root.
In central neuropathic pain, it is related to the site of the lesion in the spinal cord or brain.
Neuropathic pain responds poorly to conventional analgesics.
There is some evidence to show that opioids may have efficacy in the management of neuropathic pain.
Almost always a chronic condition (e.g. postherpetic neuralgia, poststroke pain)
Responds poorly to conventional analgesics

51. Neurophatic Pain is……?
No pain mechanism is inevitable consequence of a particular disease
One mechanism could be responsible of many different symptoms
Same symptom may be caused by different mechanism
More one mechanism can operate in a single patient (There mechanism may change with time)

52. Nociceptive afferent fiber
Ectopic discharges
Nerve lesion induces hyperactivity due to changes in ion channel function
Perceived pain
Nerve lesion
Note to speaker: this slide contains an animation illustrating the consequences of ectopic discharges from a damaged or diseased nociceptive afferent fiber. Clicking on this slide will cause subsequent components of this animation to run automatically.
The equilibrium between ion channels (e.g. sodium and potassium) in the axonal membrane of damaged or diseased neurons becomes altered.
This may result in hyperexcitability causing impulse ‘over-firing’ – also known as ectopic discharges.
Such ectopic discharges may occur spontaneously or may be evoked by mechanical stimuli (e.g. touch, pressure).
Descending modulation
Ascending input
Nociceptive afferent fiber
Spinal cord
Ectopic discharges

53. Loss of inhibitory controls
Loss of descending modulation causes exaggerated pain due to an imbalance between ascending and descending signals
Exaggerated pain perception
Noxious stimuli
Note to speaker: this slide contains an animation to illustrate the consequences of the loss of inhibitory controls following impulses in a nociceptive afferent fiber. Clicking on this slide will cause subsequent components of this animation to run automatically.
Under normal circumstances, the information transferred from the periphery to the brain depends on the balance of ascending (excitatory) and descending (inhibitory) modulation acting on dorsal horn neurons.
Under pathological circumstances, inhibitory controls may be lost or impaired, causing dorsal horn neurons to ‘over-fire’ in response to sensory input, leading to an exaggerated pain response.
Loss of descending modulation
Ascending input
Nociceptive afferent fiber
Spinal cord

54. Central sensitization
After nerve injury, increased input to the dorsal horn
can induce central sensitization
Perceived pain
Nerve lesion
Descending modulation
Ascending input
Abnormal discharges induce central sensitization
Nociceptive afferent fiber
Intact tactile fiber
Note to speaker: this slide contains an animated build to show that central sensitization involves changes at the level of the dorsal horn neurons. Clicking on this slide will cause subsequent components of the build to appear automatically.
Under normal conditions:
Activation of tactile fibers is unable to stimulate dorsal horn nociceptive neurons, therefore tactile stimuli are perceived as non-painful.
Under pathological conditions:
Abnormal ectopic discharges from damaged or diseased nociceptors induce central sensitization of spinal dorsal horn neurons.
Consequently, activation of tactile fibers is now sufficient to activate dorsal horn nociceptive neurons. Therefore, stimuli normally perceived as non-painful are now perceived as pain (e.g. allodynia).
Perceived pain (allodynia)
Tactile stimuli
Descending modulation
Ascending input

55. Recognition of neuropathic pain
Pain initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system
This slide gives an overview of neuropathic pain, with examples of common causes.
Neuropathic pain has been defined by the IASP as a pain that is “initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system”.1
Causes of peripheral neuropathic pain include postsurgical and posttraumatic nerve injury, diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN) and radiculopathies.
Poststroke pain, multiple sclerosis, and spinal cord injuries are all examples of central neuropathic pain.
Neuropathic pain is frequently described as a “shooting”, “electric shock-like”, or “burning” pain – commonly associated with “tingling” and/or “numbness”.
The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain).
In peripheral neuropathic pain, it is in the territory of the affected nerve or nerve root.
In central neuropathic pain, it is related to the site of the lesion in the spinal cord or brain.
1. International Association for the Study of Pain (IASP) pain terminology. (last accessed: 14/12/05)
Examples
Diabetic peripheral neuropathy (DPN)
Postsurgical nerve injury
Postherpetic neuralgia (PHN)
Lumbar radiculopathy
Poststroke pain
Common descriptors
Shooting
Electric shock-like
Burning
Tingling
Numbness

56. The co-presentation of nociceptive and neuropathic pain
Both types of pain co- exist in many conditions
Nociceptive pain
Neuropathic pain
The co-existence of pain types has been referred to as “mixed” or “combined” pain.
Examples of these conditions include low back pain with associated lumbar radiculopathy, cancer pain and carpal tunnel syndrome.

57. Co-existence of nociceptive and neuropathic pain
Co-existence of pain types has been referred to as either a “mixed” or “combined” pain state
Examples include low back pain associated with radiculopathy, cancer pain and carpal tunnel syndrome
Note to speaker: this slide contains an animated build. The first bullet appears automatically, then click on the slide to bring up the remaining 3 bullets sequentially.
Effective management requires a broader therapeutic approach to relieve both the nociceptive and neuropathic pain components

58. Example of co-existing pain: herniated disc causing low back pain and lumbar radiculopathy
Note to speaker: this is the first slide in the sequence illustrating co-existing pain.
Over the next 3 slides, a typical example of co-existing pain will be demonstrated using low back pain and associated lumbar radiculopathy caused by a herniated disc. These slides will show:
a patient image of low back pain caused by a herniated disc
a close-up diagram of the area of pain
an animated build showing the nervous system involvement in the pain sensation.

59. Example of co-existing pain: herniated disc causing low back pain and lumbar radiculopathy
Activation of peripheral nociceptors –cause of nociceptive pain component
Disc herniation
Note to speaker: this slide contains an animated build to represent co-presenting pain (herniated disc causing low back pain and lumbar radiculopathy). Clicking on this slide causes subsequent components of the build to appear automatically.
Nociceptive pain component:
Localized, low back pain at the site of the herniated disc is mediated by the release of inflammatory mediators from degrading cartilage cells, activating peripheral nociceptors and sending impulses along the sensory (afferent) nerves to the dorsal horn and then to the brain.
Neuropathic pain component:
Pain impulses are mediated by nerve damage following compression of the dorsal root and abnormal impulses enter the spinal cord to reach the dorsal horn.
These abnormal impulses can over-stimulate the secondary nerves ascending to the cortex through various pathways relaying in the brain stem, thalamus and limbic system where pain awareness develops.
Such nerve damage (a lesion or dysfunction at any point of the ascending or descending pathways) can cause:
Positive symptoms – spontaneous pain and tingling, radiating down to the lower legs.
Negative symptoms – weakness or loss of sensation and numbness, radiating down to the lower legs.
Broader analgesic treatment options may be required for the management of co-exisitng pain conditions to encompass both nociceptive and neuropathic elements.
Lumbar vertebra
Compression and inflammation of nerve root – cause of neuropathic pain component

60. Example of co-existing pain: herniated disc causing low back pain and lumbar radiculopathy
Constant ache, throbbing pain in the low back
Shooting, burning pain in the foot
Patient presents with both types of pain
Lesion
Note to speaker: this slide contains an animated build to represent co-presenting pain (herniated disc causing low back pain and lumbar radiculopathy). Clicking on this slide causes subsequent components of the build to appear automatically.
Nociceptive pain component:
Localized, low back pain at the site of the herniated disc is mediated by the release of inflammatory mediators from degrading cartilage cells, activating peripheral nociceptors and sending impulses along the sensory (afferent) nerves to the dorsal horn and then to the brain.
Neuropathic pain component:
Pain impulses are mediated by nerve damage following compression of the dorsal root and abnormal impulses enter the spinal cord to reach the dorsal horn.
These abnormal impulses can over-stimulate the secondary nerves ascending to the cortex through various pathways relaying in the brain stem, thalamus and limbic system where pain awareness develops.
Such nerve damage (a lesion or dysfunction at any point of the ascending or descending pathways) can cause:
Positive symptoms – spontaneous pain and tingling, radiating down to the lower legs.
Negative symptoms – weakness or loss of sensation and numbness, radiating down to the lower legs.
Broader analgesic treatment options may be required for the management of co-exisiting pain conditions to encompass both nociceptive and neuropathic elements.
Activation of local nociceptors
Ectopic discharges from nerve root lesion

61. Nociceptive and neuropathic pain may co-exist in low back pain conditions
Nociceptive pain component
Neuropathic pain component
Note to speaker: this slide contains an animated build to show both the nociceptive and neuropathic components of co-existing pain using low back pain with associated lumbar radiculopathy as the example. Clicking on this slide will cause the co-presentation component of this build to appear automatically.

62. PRESENTATION ACROSS PAIN STATES VARIES
Mixed Pain
Pain with
neuropathic and
nociceptive
components
Neuropathic Pain
Pain initiated or caused by a primary lesion or dysfunction in the nervous system (either peripheral or central nervous system)1
Nociceptive Pain
Pain caused by injury to body tissues (musculoskeletal, cutaneous or visceral)2
Examples
Peripheral
Postherpetic neuralgia
Trigeminal neuralgia
Diabetic peripheral neuropathy
Postsurgical neuropathy
Posttraumatic neuropathy
Central
Poststroke pain
Common descriptors2
Burning
Tingling
Hypersensitivity to touch or cold
Examples
Low back pain with radiculopathy
Cervical radiculopathy
Cancer pain
Carpal tunnel syndrome
Examples
Pain due to inflammation
Limb pain after a fracture
Joint pain in osteoarthritis
Postoperative visceral pain
Common descriptors2
Aching
Sharp
Throbbing
This slide illustrates three broad categories of pain: neuropathic (pathologic), nociceptive (physiologic), and mixed pain states that encompass both nociceptive and neuropathic components, with examples of common causes of each type of pain.
The key talking points on this slide are as follows:
Neuropathic pain has been defined by the International Association for the Study of Pain as ‘initiated or caused by a primary lesion or dysfunction in the nervous system’.1 Depending on where the lesion or dysfunction occurs within the nervous system, neuropathic pain can be peripheral or central in origin.
Causes of peripheral neuropathic pain include postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN). Due to the prevalence and characteristics of PHN and DPN, these states may be considered representative of peripheral neuropathic pain.
Nociceptive pain is an appropriate physiologic response that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli. Nociceptive pain has a protective role because it elicits reflex and behavioral responses that keep tissue damage to a minimum.
Acute pain, such as that seen with tissue inflammation and chronic pain, such that accompanying osteoarthritis, are examples of nociceptive pain.
Although there are no specific descriptors for each type of pain, neuropathic pain is frequently described as ‘burning or tingling’ in quality, while nociceptive pain is often described as ‘aching or throbbing’.
There are cases in which an individual experiences pain sensations that are a blend of pain having a nociceptive and a neuropathic origin. For example, in carpal tunnel syndrome, it is common experience to have nociceptive pain, felt around the wrist, and neuropathic pain, felt in the distribution territory of the median nerve (fingers).
References
International Association for the Study of Pain. IASP Pain Terminology.
Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited ;11-57
Additional key words: descriptor
1. International Association for the Study of Pain. IASP Pain Terminology.
2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed ;11-57

63. Chronic pain ?
Chronic pain is a pain that persists beyond normal tissue healing time, which is assumed to be three months.
The International Association for study of pain (IASP)

64. panthom pain

65. PATHOPHYSIOLOGY OF CHRONIC PAIN
Pathophysiology in CNS - “central sensitization”
“Rewiring” in spinal cord dorsal horn
Genetic changes in dorsal horn neurons
Death of neurons: inhibitory deficit
Inhibition of normal motor activity, muscle wasting
Sympathetic dysfunction, tropic changes

66. CONSEQUENCE of CHRONIC PAIN
Fear - avoidance behaviour
Anxiety and sleep disturbance
Depression, helplessness, irritability, suicidal risk
CNS toxicity due to inappropriate drug use
Loss of job, family and community status

67. CHRONIC PAIN IS A DISEASE ENTITY
Is a major problem of public health
lead to emotional distress and suffering (insomnia, anxiety, depression,can not work, etc)
Is really a killer for quality of life

68. Conclution
1. -Pain is a very subjective feeling -Pain is what ever the patient says 2. -Only nociceptive pain is respond to NSAID (cox1 or cox2) 3. -Neurophatic pain do not respond to NSAID but it may respond to antidepressants or anticonvulsants may be opioid Chronic pain, is pain beyond naciceptive, occur after healing process, difficult to treat and reduced quality of life.

69. Take Home Message
It’s important to more understanding PAIN, type and characteristic of pain..
Because…
In many parts of Indonesia :
Many people may die in pain, but
Many more people dying with pain,
Even many more people living in pain
This is our task to help them as a Doctor

70. The task of a doctor: TO CURE IS SOMETIMES TO TREAT IS OFTEN
TO COMFORT IS ALWAYS
A. Pare (1598)