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, Kandy08.10.2011

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.

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!

The concept that pain is a visitation from a just God dates at least from the earliest days of Christianity

Genesis 3:16

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.

• 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

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.

So…. What is Pain?

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)

Pain is what the patient says it is!

Never deny patients symptoms for “?FUNCTIONAL ILLNESS”

PAIN

Biological

Psychological Social

Classification• Aetiological

– 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

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

PAIN: an Alarm?

True for Acute Pain which is an ALARM.Chronic Pain is a false alarm; it is a

disease.

Acute Pain (Nociceptive)

Chronic Pain (Neuropathic) without ongoing tissue damage (Nociceptive)

Pain

Chronic Pain (Neuropathic) with ongoing tissue damage (Nociceptive) - Mixed

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).

• 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

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.

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

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)

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.

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.

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.

Gate-Control Theory

Brain

Spinal Cord

GatingMechanism

TransmissionCells

Frompainfibers

FromotherPeripheralfibers

Tobrain

Brain

Spinal Cord

GatingMechanism

TransmissionCells

Frompainfibers

FromotherPeripheralfibers

Tobrain

Gate is open Gate is closed

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.

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.

What is Sensitization?

Sensitization is a phenomenon of inappropriate or disproportionate response

to normal stimulus

Peripheral Sensitization Central Sensitization

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.

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

Results of Sensitization 1. Increased intensity of pain.2. Increased area of pain.3. Increased duration of pain.4. Allodynia5. Decreased tolerability to pain.6. Development of psychological

problems (e.g.. depression due to decreased serotonin level).

7. Pain become non-responsive to conventional analgesics.

Pain

SensitizationDecreased tolerance

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.

Consequences of Unrelieved Pain Cardiovascular

• Hypercoagulability• Increased heart rate, blood pressure• Increased cardiac workload• Increased oxygen demand• Increased risk of myocardial infarction

Consequences of Unrelieved Pain Respiratory

• Diminished respiratory function• Decreased alveolar ventilation• Pneumonia• Atelectasis• Pulmonary embolism• Hypoxia• Slowed wound healing

Consequences of Unrelieved PainGastrointestinal

• Delayed gastric emptying• Decreased motility• Illus• Anorexia/weight loss

Consequences of Unrelieved PainMusculoskeletal

• Muscle spasm• Impaired muscle function• Decreased mobility• Decreased ability to ambulate• Diminished short- and long-term recovery

& rehab

Consequences of Unrelieved PainCognitive

• Mental status changes• Confusion• Sleep disturbance• Depression• Behavior disturbances• Anxiety• Anhedonia

Consequences of Unrelieved PainPersonal

• Inability to perform ADL’s/loss of independence

• Impaired relationships with family/friends• Impaired intimacy/sexual activity• Social Isolation• Anger• Loss of self-esteem

Pain Assessment

• Type of Pain & Aetiology• Severity of Pain • Disability (Physical/

Psychological)• Treatment in Progress

Pain Assessment Pain Scales

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

Treatment of ( Mainly Chronic) Pain: MUTIMODAL APPROACH

Combination Analgesics Adjuvant Therapy

Interventional Pain Management

Physical MedicinePsychological Intervention

Treatment Strategies1. Eliminate barriers to effective pain

management

2. Clarifying controversial issues in pain management

3. Non-medicinal treatment methods

4. Appropriate medications for pain relief

5. Interventional pain management

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

Treatment Strategies1. Eliminate barriers to effective pain

management

2. Clarifying controversial issues in pain management

3. Appropriate medications for pain relief

4. Non-medicinal treatment methods

5. Interventional pain management

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.

• “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

Treatment Strategies1. Eliminate barriers to effective pain

management

2. Clarifying controversial issues in pain management

3. Appropriate Non-Medical & medications for pain relief

4. Interventional pain management

Acute Pain (Nociceptive)

Chronic Pain (Neuropathic) without ongoing tissue damage (Nociceptive)

Pain

Chronic Pain (Neuropathic) with ongoing tissue damage (Nociceptive) - Mixed

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

Aims of Medical Treatment

Non-pharmacological methods

Non-opioids

Weak opioids +/- non-opioids +/- adjuvant

Strong opioids

Recovery?

Surgical Destruction of Neuro-pathways

Treatment of Pain

Missing linkBetween Med & Sx

Mx

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

Non Pharmacological

Non-pharmacological methods

Non-opioids

Weak opioids +/- non-opioids +/- adjuvant

Strong opioids

Recovery?

Operation

Treatment of Pain

• 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.

NSAIDS

Appears to be more involved than previously thought peripheral action only.

Centralaction

Differencesin

isomer activity

NSAIDS- mechanism of action

Multiple isoforms of cyclooxygenase

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

• 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

COX selectivty- 4 classes

• 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.

Toxicity

• Age > 50 years• Past history of peptic ulcer• Steroid use• Alcohol use• Multiple NSAIDs use• First 3 months of use

NSAIDs- GI toxicityRisk • 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.

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

Non-pharmacological methods

Non-opioids

Weak opioids +/- non-opioids +/- adjuvant

Strong opioids

Recovery

Operation

Treatment of Pain

OPIOIDS CLASSIFICATION• NATURAL

• Morphine.• Codiene.• Theibene.

• SEMISYNTHETIC• Pethidine.• Oxycodone.

• SYNTHETIC• Fentanyl.

• PURE AGONIST• Morphine.• Fentanyl.

• PARTIAL AGONIST• Buprenorphine.

• AGONIST- ANTAGONIST• Nalbuphine.

• ANTAGONIST• Naloxone • Naltrexone.

• Mu• Analgesia• Respiratory

depression.• Nausea,

Vomiting.• Kappa

• Hallucination.• Delta

• Spinal Analgesia.

Endogenous• Endorphines• Enkephalines• Dynorphines

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

Tramadol 

• Opioid receptor agonist (mu and delta) • NE and 5-HT reuptake blocker

(antidepressant) • α-2 adrenoceptor agonist • These actions are synergistic for analgesia

Non-pharmacological methods

Non-opioids

Weak opioids +/- non-opioids +/- adjuvant

Strong opioids

Recovery

Operation

Treatment of Pain

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

Other Adjuvants

Non-pharmacological methods

Non-opioids

Weak opioids +/- non-opioids +/- adjuvant

Strong opioids

Recovery

Operation

Treatment of Pain

End of Pharmacotherapy ???

*finally, there is some evidence for a variety of (new) drugs

Non-opioids

Weak opioids +/- non-opioids

Strong opioids

Recovery

Operation

Treatment of Pain

World of Misery Non-pharmacological methods

Treatment Strategies1. Eliminate barriers to effective pain

management

2. Clarifying controversial issues in pain management

3. Appropriate medications for pain relief

4. Non-medicinal treatment methods

5. Interventional pain management (IPM)

Non-opioids

Weak opioids +/- non-opioids

Strong opioids

Recovery

Operation

Treatment of Pain

Non-pharmacological methods

• 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)

Interventional Pain Management

John Bonica ‘The Godfather ‘of Interventionalism

Norman Harden Center for Pain Studies Rehabilitation Institute, Chicago Northwestern University

The Evidence

few RCTs of Interventions in Pain…so far!

• Randomization Ethics• Control ?• Blinding Impossible ?• Economic• Referral Bias• What outcome?

Flavors of interventions:

• Injections (squirt) – Local/Spinal/ ITDD• Ablation (burn) – Cryo/RF• Electro-stimulation (shock) –

Peripheral / cord Stimulation• Surgery (slash)

Pros & Cons

• Bridges the gap• Targeted therapy

• Invasive but Safe in Skilled hands

• Cost• Patient/Procedure selection

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

Most Important Consideration of IPM…..

• Correct Procedure on Correct patient.

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%

• 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

• 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%

• 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%

Thanks