1. When Pain Becomes a Disease Than a Symptom!
Dr R Jayamaha MBBS(Col), MD(SL), FIPP(USA)
Consultant Physician
Special Interest in Interventional Pain Practice
Teaching Hospital, Kandy

2. History of Pain… Pain; Gods Punishment?
In 1591 Eufan MacAyane of Edinburgh, a young mother, was dragged from her home and taken away. Her pleas for mercy were ignored, and she was thrown into a pit and buried alive.

3. So What Was Her Crime?
She had just given birth to twin sons and during her difficult labor she had asked for pain relief. The church’s teachings of the day regarded the pain of childbirth as a punishment justly inflicted by God!

4. The concept that pain is a visitation from a just God dates at least from the earliest days of Christianity Genesis 3:16

5. It may be even older…..
Among Egyptian papyri from as much as 4500 years ago there are clear descriptions of what would have been painful surgical procedures.
Although certain herbs were available at that time, that could relieve pain, and were discussed in other papyri, the surgical descriptions themselves make no mention of them.

6. By A.D. 150 to A.D. 200 a few Greek and Roman surgeons were giving herbs that not only relieved pain but also put the patient to sleep, thereby approaching the capabilities of modern anesthetists.
In fact Dioscorides, a Greek army surgeon who was first to use the term Anesthesia

7. But these isolated measures did not spread in Christian Europe
In later centuries Muslim physicians did begin to use various herbs for the relief of pain, soaking a sponge in the appropriate herbs to be inhaled by the patient known as soporific sponges.
They were introduced in Christian Europe by monks between the fourteenth and seventeenth centuries.

8. So…. What is Pain?

9. By Definition Pain is…
“An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, or both.”
International Association for the Study of Pain ( IASP:2001)

10. Pain is what the patient says it is!
Never deny patients symptoms for “?FUNCTIONAL ILLNESS”

11. Biological
PAIN
Social
Psychological

12. Classification Acute (<3months) Aetiological Chronological
Nociceptive pain
Is pain from pain receptor stimulation. It may be somatic pain from activation of receptors in the musculoskeletal system or visceral pain which arises from receptors in the viscera.
Neuropathic pain
Is due to changes in the peripheral or central nervous system.
Idiopathic pain?
Is pain without a known cause, and is not a diagnosis of psychogenic pain.
Chronological
Acute (<3months)
A response to injury or illness
Time limited
Usually responsive to treatment
Inadequate treatment delays recovery
Chronic (>3months)
A state in which pain persists beyond the usual course of an acute disease or healing of an injury, or that may or may not be associated with an acute or chronic pathologic process that causes continuous or intermittent pain over months or years

13. Types of Pain Acute Pain /Physiological Pain Nociceptive
Symptom of a disease
Treatment of diseases cures pain & it is self-limiting.
Simple relationship between pain and tissue damage
Proportionate to the clinical finding
Chronic Pain /Pathological Pain
Mostly Neuropathic
A disease itself (a disease of nervous system).
Difficult to treat & sustaining.
Dissociated relationship between pain and tissue damage
Disproportionate to the clinical finding

14. PAIN: an Alarm?
True for Acute Pain which is an ALARM. Chronic Pain is a false alarm; it is a disease.

15. Pain Acute Pain (Nociceptive)
Chronic Pain (Neuropathic) with ongoing tissue damage (Nociceptive) - Mixed
Chronic Pain (Neuropathic) without ongoing tissue damage (Nociceptive)

16. Why Bother So Much? In US………….
It is estimated that approximately 1/3 of the population suffers from chronic pain and up to 9% of adults suffer from moderate to severe non-cancer related chronic pain (American Pain Society [APS], 2002).
In addition, chronic pain is estimated to affect 15% to 20% of children (Goodman & McGrath, 1991).

17. Pain – 76.2 million people, National Centers for Health Statistics
Diabetes – 20.8 million people (diagnosed and estimated undiagnosed), American Diabetes Association
Coronary Heart Disease (including heart attack and chest pain) and Stroke – 18.7 million people, American Heart Association
Cancer – 1.4 million people, American Cancer Society

18. Statistics on Duration
Adults 20 years of age and over who reported having pain said that it lasted:
Less than one month – 32%
One to three months – 12%
Three months to one year – 14%
Longer than one year – 42%
The suicide rate among pain patients is almost 20 times greater than all other patients because of inadequate relief.
As many as 75% of even cancer pain patients receive grossly inadequate pain relief.
Because of this, the suicide rate among pain patients is almost 20 times that of all other patients.

19. Inadequate Pain Treatment Can Lead To…
Lost productivity
Excessive healthcare expenditures
Needless suffering
Domestic and occupational problems
Increased thoughts and risk of suicide
(American Pain Society, 2001: National Conference of State Legislatures, 1999)
The economic burden of chronic pain as high as
$100 billion annually in US
These factors have driven estimates of the economic burden of chronic pain as high as $100 billion annually

20. How is pain processed?
Pain results from a series of exchanges among three major components of your nervous system:
Nociceptors / Peripheral nerves (transduction/ transmission)
Spinal cord (+Modulation/neuroplasty)
Brain (Perception/reorganization)

21. Nociceptors Most concentrated in areas prone to injury
Such as fingers and toes.
When nociceptors detect a harmful stimulus
They generate a pain message in the form of an electrical impulse along a peripheral nerve to your spinal cord and brain.
They can be epicritic (A-δ/ Fast) or protopathic (C- Slow) pains.

22. Spinal cord Nerve fibers that transmit pain
messages enter the spinal cord in an area called the dorsal horn.
There, they release chemicals (neurotransmitters) that activate other nerve cells in the spinal cord, which process the information and then transmit it up to the brain.

23. Gate-Control Theory: Ronald Melzack (1960s)
Described physiological mechanism by which psychological factors can affect the experience of pain.
Neural gate can open and close thereby modulating pain.
Gate is located in the spinal cord.

24. Gate-Control Theory From pain fibers other Peripheral To brain From
Spinal Cord
Gating
Mechanism
Transmission
Cells
From
pain
fibers
other
Peripheral To
brain
Brain
Spinal Cord
Gating
Mechanism
Transmission
Cells
From
pain
fibers
other
Peripheral To
brain
Pain signals arrive from the pain fibers (A-delta and C) at the spinal cord, along with signals from other peripheral fibers (A-beta) and the brain. The solid arrows depict stimulation conditions that tend to open the gate and send pain signals through. The dotted arrows indicate inhibition conditions. Pain signals enter the spinal cord and pass through a gating mechanism before activating transmission cells, which send impulses to the brain (from text by Sarafino EP. Health Psychology, Biopsychosocical Interactions, Third Edition. John Wiley & Sons, Inc. New York: 1998.)
Gate is open
Gate is closed

25. Three Factors Involved in Opening and Closing the Gate
The amount of activity in the pain fibers.
The amount of activity in other peripheral fibers
Messages that descend from the brain.

27. The Brain
When messages travel up the spinal cord, it arrives at the thalamus
a sorting and switching station deep inside your brain.
The thalamus forwards this message simultaneously to three specialized regions of the brain:
Somatosensory cortex - the physical sensation region
Limbic system - the emotional feeling region
Frontal cortex - the thinking region
The brain then responds to pain by sending down messages which moderate the pain in the spinal cord.

28. What is Sensitization?
Sensitization is a phenomenon of inappropriate or disproportionate response to normal stimulus
Peripheral Sensitization
Central Sensitization

29. Peripheral sensitization
Sensitization of primary afferent terminals.
Active nociceptors become sensitized and sleeping nociceptors awaken.
Damaged axons sprout, forms collaterals.
Ectopic discharges along nerve axon, terminals & at DRG.
SNS fibers invade DRG- CRPS
Phenotypic switch in expression of neuropeptides like Sub P, CGRP.

31. Central Sensitization
Central Re-organisation.
Wind up (summation of signals)
Up-regulation of NMDA receptor
Ectopic activity
Depression inhibitory synapses
Activation of WDR cells.

32. Results of Sensitization
Pain
Sensitization
Decreased tolerance
Increased intensity of pain.
Increased area of pain.
Increased duration of pain.
Allodynia
Decreased tolerability to pain.
Development of psychological problems (e.g.. depression due to decreased serotonin level).
Pain become non-responsive to conventional analgesics.

33. Symptoms of chronic pain
Pain in the area of neuro-deficit.
Allodynia, Hyperalgesia
Character of pain: Burning, shooting, electric shock-like, stabbing pain.
Associated symptoms: Numbness, tingling, pruritus, feeling of pin & needles.
SMP: redness, edema, painful joint movements, decreased skin temperature, fall of hairs.

34. Consequences of Unrelieved Pain Cardiovascular
Hypercoagulability
Increased heart rate, blood pressure
Increased cardiac workload
Increased oxygen demand
Increased risk of myocardial infarction

35. Consequences of Unrelieved Pain Respiratory
Diminished respiratory function
Decreased alveolar ventilation
Pneumonia
Atelectasis
Pulmonary embolism
Hypoxia
Slowed wound healing

36. Consequences of Unrelieved Pain Gastrointestinal
Delayed gastric emptying
Decreased motility
Illus
Anorexia/weight loss

37. Consequences of Unrelieved Pain Musculoskeletal
Muscle spasm
Impaired muscle function
Decreased mobility
Decreased ability to ambulate
Diminished short- and long-term recovery & rehab

38. Consequences of Unrelieved Pain Cognitive
Mental status changes
Confusion
Sleep disturbance
Depression
Behavior disturbances
Anxiety
Anhedonia

39. Consequences of Unrelieved Pain Personal
Inability to perform ADL’s/loss of independence
Impaired relationships with family/friends
Impaired intimacy/sexual activity
Social Isolation
Anger
Loss of self-esteem

40. Pain Assessment Type of Pain & Aetiology Severity of Pain
Disability (Physical/ Psychological)
Treatment in Progress

41. Pain Assessment Pain Scales
No one will treat hypertension without BP measurement BUT everyone tends to treat without measuring it…..

42. Treatment of ( Mainly Chronic) Pain: MUTIMODAL APPROACH
Combination Analgesics
Adjuvant Therapy
Interventional Pain Management
Physical Medicine
Psychological Intervention

43. Treatment Strategies Eliminate barriers to effective pain management
Clarifying controversial issues in pain management
Non-medicinal treatment methods
Appropriate medications for pain relief
Interventional pain management

44. 1.Barriers to Effective Pain Management
Care Providers: Inadequate knowledge re: pain and its management, fear of side effects, fear of regulatory retributions
Patients: Exaggerated fear of addiction, belief that pain is normal/inevitable part of aging
Health Care System: dissuades opioid use, under-utilization of pain specialists due to insufficient knowledge of benefit

45. Treatment Strategies Eliminate barriers to effective pain management
Clarifying controversial issues in pain management
Appropriate medications for pain relief
Non-medicinal treatment methods
Interventional pain management

46. 2.Controversial Issues in Pain Management
Addiction
Primary, chronic, neurobiologic disease, characterized by a persistent pattern of dysfunctional opioid use with Preoccupation with obtaining opioids despite adequate analgesia
Pseudo-addiction
A set of behaviors a person exhibits to obtain adequate pain relief like becomes focused on obtaining meds, clock watching, may seem to be “drug seeking”, may resort to doctor shopping, deception, to obtain adequate relief. Behaviors resolve when pain treated effectively
Dependence
A state of adaptation manifested by a specific drug class withdrawal syndrome produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.
Tolerance
A state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Tolerance may develop with opioid side effects (e.g. respiratory depression, drowsiness). Exceeding tolerance can be fatal.

47. “Controlled substances have legitimate clinical usefulness and the prescriber should not hesitate to consider prescribing them when they are indicated for the comfort and well being of the patient.”
D.E.A. Physician’s Manual

48. Treatment Strategies Eliminate barriers to effective pain management
Clarifying controversial issues in pain management
Appropriate Non-Medical & medications for pain relief
Interventional pain management

49. Pain Acute Pain (Nociceptive)
Chronic Pain (Neuropathic) with ongoing tissue damage (Nociceptive) - Mixed
Chronic Pain (Neuropathic) without ongoing tissue damage (Nociceptive)

50. Aims of Medical Treatment
Treatment of Acute Pain
Source + Pain Control
Non Pharmacological methods
NSAIDs for a very short period
Paracetamol in adequate doses
Tramadol + Paracetamol in adequate doses
Regional analgesia
Treatment of Chronic Pain with Tissue Damage
Source + Pain Control + Correcting neuropathy/ central sensitization
Treatment of Chronic Pain Without Tissue Damage
Correcting neuropathy/ central sensitization
Treatment for peripheral sensitization
Na-Channel blocker, Ca-Channel blocker
Treatment for central sensitization
NMDA antagonist, Ca-Channel blocker, Opioids, drugs inhibiting Sub P, drugs enhances inhibitory synapses.
Restoration of descending inhibitory pathways
Tramadol OR Tricyclics

51. Treatment of Pain Recovery? Strong opioids Missing link
Surgical Destruction of Neuro-pathways
Strong opioids
Missing link
Between Med & Sx Mx
Weak opioids +/- non-opioids +/- adjuvant
Non-opioids
Non-pharmacological methods

52. Non Pharmacological Diet (e.g.. Migraine) Exercise
Biofeedback/relaxation training
Acupuncture
Consistent sleep/wake cycles

53. Treatment of Pain Recovery? Operation Strong opioids
Weak opioids +/- non-opioids +/- adjuvant
Non-opioids
Non-pharmacological methods

54. NSAIDS
NSAIDs are the most widely prescribed drugs for the treatment of acute and chronic pain , which account for about 6 to 7 billion dollars P.A in sales worldwide.

55. NSAIDS- mechanism of action
Differences in
isomer activity
Central
action
Multiple isoforms of cyclooxygenase
Appears to be more involved than previously thought peripheral action only.

56. NSAIDs: Mechanism of Action
Inhibits cyclooxygenase- prevents sensitization of peripheral Nociceptors by diminishing PG formation- most commonly stated.
Cellular effects unrelated to PGs-inhibits release of inflammatory mediators from neutrophils & macrophages.
Also produces analgesia through CNS mechanism- by reversing inhibition by PGs of opioid-mediated pain modulation

57. COX selectivty- 4 classes
I- Aspirin- irreversible inhibition of both COX-1 & COX-2.
II- Ibuprofen-reversible competitive inhibition of both isoforms.
III-Flurbiprofen-slower time dependent inhibition of both isoforms. Also enhances NO production in gastric mucosa
IV-Celecoxib- largely COX-2 selective

58. Toxicity Gastrointestinal effects. Cardiovascular effects.
Renal toxicity
Renal impairment in 18%, ARF in 6% using NSAIDs. Clinically significant in patients with Heart failure, Renal insufficiency & Liver disease
Hepatic toxicity.
Liver related side effects reported in 3% users.
Sulinduc creates higher risk of hepatic damage, although mild& reversible.
Diclofenac with fulminant hepatitis reported
Allergy and hypersensitivity.
Hematologic effects.
Aspirin inhibits platelet activation irreversibly- takes 7-10 days to recover.
Non-aspirin NSAIDs include reversible platelet inhibition – resolves when drug is eliminated
Most NSAIDs potentiate anticoagulant activity of warfarin.
CNS effects.

59. NSAIDs- GI toxicity
Risk
The ARAMIS model for estimating risk of Gastric ulceration while taking nonselective NSAIDs.
A score > 1.5 is considered high risk and a contraindication for the use of nonselective NSAIDs.
The scale is for chronic use over a 12 month period.
Age > 50 years
Past history of peptic ulcer
Steroid use
Alcohol use
Multiple NSAIDs use
First 3 months of use
Step 1 Start at a score of 0 Step 2 Add 0.3 for every 5 y of patient’s age over 50 y Step 3 Add 1.2 if the pt is receiving a corticosteroid Step 4 Add 1.4 if the pt has reported a previous NSAID- related GI side-effects Step 5 Add 0.5 if the pt has sustained disability

60. Treatment of Pain Recovery Operation Strong opioids
Weak opioids +/- non-opioids +/- adjuvant
Non-opioids
Non-pharmacological methods

61. OPIOIDS CLASSIFICATIONMu
Analgesia
Respiratory depression.
Nausea, Vomiting.
Kappa
Hallucination.
Delta
Spinal Analgesia.
NATURAL
Morphine.
Codiene.
Theibene.
SEMISYNTHETIC
Pethidine.
Oxycodone.
SYNTHETIC
Fentanyl.
PURE AGONIST
Morphine.
Fentanyl.
PARTIAL AGONIST
Buprenorphine.
AGONIST- ANTAGONIST
Nalbuphine.
ANTAGONIST
Naloxone
Naltrexone.
Endogenous
Endorphines
Enkephalines
Dynorphines

62. Codeine About 1/10th the potency of morphine
lower efficacy than morphine
about 10% converted to morphine by CYP450 2D6
10% of patients do not possess this enzyme

63. Tramadol Opioid receptor agonist (mu and delta)
NE and 5-HT reuptake blocker (antidepressant)
α-2 adrenoceptor agonist
These actions are synergistic for analgesia

64. Treatment of Pain Recovery Operation Strong opioids
Weak opioids +/- non-opioids +/- adjuvant
Non-opioids
Non-pharmacological methods

65. Other Adjuvants Anticonvulsants
Traditionally used for neuropathic pain-carbamazepine and phenytoin.
Newer agents- gabapentin, pregabalin, lamotrigine.
Gabapentin and carbamazepine- are more evidence based.
Pregabalin and lamotrigine- no systematic review or meta-analysis of trials available at present.
Pregabalin – higher doses(300 to 600 mg/day) produces more consistent results than lower doses(75 to 150 mg/day).
Complications: sedation-somnolence, fatigue, dry mouth etc.
Antidepressants
Also traditionally used for neuropathic pain.
TCAs may be most effective classes of drugs.
Amitriptyline – NNT=2, desipramine-NNT=2.1
Not effective in HIV-related neuropathies.
Other Rx
Lidocaine and mexiletine are equivalent to morphine, gabapentin, TCAs .
Lidocaine IV up to 5mg/kg over 3 to 45 min.
Mexiletine 100 to 200mg three times per day(upto 675mg TID reported).
Lidocaine 5% transdermal also effective
2-adrenergic receptor agonist- clonidine
NMDA receptor antagonist (Ketamine..)
capsaicin

66. Treatment of Pain Recovery Operation Strong opioids
Weak opioids +/- non-opioids +/- adjuvant
Non-opioids
Non-pharmacological methods

67. End of Pharmacotherapy ???
*finally, there is some
evidence for a variety
of (new) drugs

68. Treatment of Pain World of Misery Recovery Operation Strong opioids
Weak opioids +/- non-opioids
Non-opioids
World of Misery
Non-pharmacological methods

69. Treatment Strategies Eliminate barriers to effective pain management
Clarifying controversial issues in pain management
Appropriate medications for pain relief
Non-medicinal treatment methods
Interventional pain management (IPM)

70. Treatment of Pain IPM Recovery Operation Strong opioids
Weak opioids +/- non-opioids
Non-opioids
Non-pharmacological methods

71. Interventional Pain Management are some minimally invasive procedures done under image guidance which gives permanent/long term pain relief by stopping nociceptive inputs or correcting neuropathy.
It fills the gap between pharmacologic management of pain & more invasive operative procedure. (The missing link)
IPM

72. Interventional Pain Management
John Bonica
‘The Godfather ‘of Interventionalism
Norman Harden Center for Pain Studies Rehabilitation Institute, Chicago Northwestern University

73. The Evidence

74. Interventions in Pain…so far!
few RCTs of
Interventions in Pain…so far!
Randomization Ethics
Control ?
Blinding Impossible ?
Economic
Referral Bias
What outcome?

75. Flavors of interventions:
Injections (squirt) – Local/Spinal/ ITDD
Ablation (burn) – Cryo/RF
Electro-stimulation (shock) – Peripheral / cord Stimulation
Surgery (slash)

76. Pros & Cons Bridges the gap Targeted therapy
Invasive but Safe in Skilled hands
Cost
Patient/Procedure selection

77. Scope for IPM…..
Neuralgias e.g. Trigeminal Neuralgia, Post Herpetic neuralgia, Migrain/CH, IFP
Chronic spinal Pain XDs e.g. Facet J. A, Discogenic Pain, FBSS
Vertibroplasty
Complex Regional Pain XD
Cancer Pain

78. Most Important Consideration of IPM…..
Correct Procedure on Correct patient.

79. Questionnaire…? wathupitiwala\Wathupitiwala.doc
1. Pleases select the type of your practice
General Practitioner 12%
Specialist 88%
Other (please specify)
2. If you consider all pain syndromes…
All can be treated successfully
Many can be treated successfully 56%
Some can be treated successfully 38%
A few can be treated successfully 6%

80. 3. Why in your opinion some patients cannot be cured of pain?
Wrong diagnosis 34%
Wrong / inadequate treatment (including not enough drug categories/ groups) 50%
Late presentations 19%
Pain has become a disease 37%
There is a missing link between medical& surgical management of pain 35%
Drug addicted patients 3%
4. Can you enumerate such difficult situations (mainly chronic pain condition) you came across and how did you manage get away with those (chronic) patients? a b c

81. 5. If your patient has a chronic pain, If he/she is not a drug addict and if Psychiatric assessment is normal,…also if there is no medically or surgically correctable cause....what can you offer them?
Ignore their complains and discharge from follow up 9%
Continue a cocktail of analgesics/adjuvant drugs 27%
Prescribe them anti-depressants anyway 35%
Continuously investigating them for a cause 35%
Other (please specify)
 6. What are the various modalities of pain treatment available except treating underlying condition, specifically for chronic pain conditions?
TENS (transcutaneous electrical nerve stimulation) therapy 56%
Meditation 65%
Relaxation / Distraction techniques 65%
Visual imagery, as simple as picturing a peaceful scene, for example 37%
Biofeedback, which teaches control over muscle tension, temperature, heart rate and more 53%
Heat, cold or irritant application 65%
Manipulation and massage 60%
Surgically destroying pain pathways 60%
Other (please specify) 22%

82. 7. If your patient is not benefiting all these and not consenting or not a candidate for surgery…is there a possible escape route?
Yes 69%
If "Yes" what would be that possible modality???
No 31%

83. Thanks