PAIN

(NOCICEPTIC AND NEUROPATHIC)

Yudiyanta Pain Sub-Dept. of Neurology GMU

KUNJUNGAN POLIKLINIK SARAF RSS TH 2006

6000 4957 (44%) 5000
Cefalgia 20% Neuropati 9% Myalgia 4% LBP 39%

4000 2850 (25%) 3000 1731 (15%)

Atralgia 28%

2000

1000

626 (6%)

451 (4%)

217 (2%)

498 (4%)

0 Nyeri Stroke Epilepsi Vertigo Parkinson Hipertensi Lain-lain

Defining of Pain Pain Experience

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
International Association for the Study of Pain (IASP) 1994, Kyoto Protocol IASP 2008

Pain is a personal, subjective experience that comprises : Sensory-discriminative, Motivational-affective and Cognitive-evaluative dimensions
Ronald Melzack, Textbook of Pain 4th edition

Catastrophization

?????

Classification of Pain
Physiologic / nociceptive:1
Pain arising from activation of nociceptors Caused by mild and short noxious impulses which usually relieved without any medication or mild analgesics Example: Pinched, stung by mosquito

Inflammatory:2
Pain caused by injury to body tissues (musculoskeletal, cutaneus or visceral) Example: Pain due to inflammation, limb pain after fracture

Neuropathic:1
Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system Example: DPN, PHN

Psychogenic (functional):3
Pain due to abnormal responsiveness or function of the nervous system without neurologic deficit or peripheral abnormality. Example: Fibromyalgia, irritable bowel syndrome

Type or Category of Pain

3. Psychogenic clear that no somatic disorder is present 4. Mixed type Caused by a combination of both primary injury or secondary effects
sprain Inflamation / Infection Muscle Stretch

1. NociceptiveInflamatorik Caused by activity in neural pathways in response to potentially tissue-damaging stimuli

2. Neuropathic Initiated or caused by primary lesion or dysfunction in the nervous sys.

fracture / Postoperative Ongoing or impending injury

strangulated (scar tissue)

inflamed (infection )

Myofascial pain

Infiltrated or compressed (tumors)

The Assessment of the Patient with Pain, Steven Richeimer, M.D. Director USC Pain Management, USC Medical Center, Los Angeles, CA, USA, 2007

The Continuum of Pain1

Insult Time to resolution
Acute Pain Chronic Pain

<1 month

3-6 months

Usually obvious tissue damage Increased nervous system activity Pain resolves upon healing Serves a protective function

Pain for 3-6 months or more2 Pain beyond expected period

of healing2

Usually has no protective

function3

Degrades health and function3

1. Cole BE. Hosp Physician. 2002;38:23-30. 2. Turk and Okifuji. Bonicas Management of Pain. 2001. 3. Chapman and Stillman. Pain and Touch. 1996.

There are Two Sensory Afferent Neurons

1. Large myelinated A fibers Very fast conduction velocity Respond to innocuous stimuli 2. Small myelinated A & C unmyelinated fibers Slow conduction velocity Respond to noxious stimuli

Large fibers

A Small fibers C Peripheral sensory Nerve fibers

Dorsal root ganglion

Dorsal Horn

Small-fiber sensory -Burning pain -Allodinia -Hyperalgesia -Hyperesthesia -Paresthesia/dysesthesia -Lancinating pain -Loss of pain & temp. sensation -Foot ulceration -Loss of visceral pain

Large-fiber sensory -Loss of vibration -Loss of proprioception -Loss of reflexes -Slowed NCV

Autonomic -Heart rate abnormalities -Postural hypotension -Abnormal sweating -Gastroparesis -Neuropathic diarrhea -Impotence -Retrograde ejaculation

Normal Nerve Impulses Leading to Pain

Perceived pain

Noxious stimuli Descending modulation Ascending input

Nociceptive afferent fiber Spinal cord

Perception

Nociception

Pain

Modulation
Descending modulation Ascending input Dorsal Horn Dorsal root ganglion

Transmission 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.

Transduction
Si-Na+ R-NE Pengalaman Kognitif Behaviour Psikologik

KERUSAKAN JARINGAN INFLAMASI

SENSITISASI
SSA ECT. DISC. MI NOS AKTIFASI Pg B, 5HT, Adenosin KORNU DORSALIS Inhibisi desenden OTAK PAIN NO PAIN

Activation

External Heat
Mechanical

VR1 Ca2+

Pain and auto-sensitization

Na+

POTENTIAL mDEG ACTION ACTION POTENTIAL Voltage gated sodium channels P2X3

Stimuli

ATP Chemical

action potentials Generator potentials

Woolf & Mitchel, 2001 Modifikasi Meliala, 2003

Anger

Anxiety

Fear

Depression
A
B

NOCICEPTIVE

Noxious Stimuli

MELIALA 2004

What is Inflammatory Pain?

Often classed along with acute pain as nociceptive, refers to the spontaneous pain and tenderness felt when tissue is inflamed.

Pain caused by injury to body tissues (musculoskeletal, cutaneous or visceral)

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) Can also be chronic (e.g. osteoarthritis, rheumatoid arthritis)

Usually responsive to NSAIDs

NOCICEPTIVE PAIN

Inflammation Tissue
1
Painful stimulus

Prostaglandins produced in response to tissue injury; increase sensitivity of nociceptor (pain)

Pain-sensitive tissue

Prostaglandin

2 1
Substance P Blood vessel

Mast cell
Histamine

Nociceptor then releases substance P, which dilates blood vessels and increases release of inflammatory mediators, such as Bradykinin (redness & heat) Substance P also promotes degranulation of mast cells, which release histamine (swelling)

Bradykinin Substance P

3
Nociceptor

What is Neuropathic pain?

Definition:
Pain arising as a direct consequence of a lesion or disease affecting the somatosensory NERVE system

Characterized by:
Pain often described as shooting, electric shock-like or burning.

The painful region may not necessarily be the same as the site of injury.
Almost always a chronic condition (e.g. post herpetic neuralgia, post stroke pain) Responds poorly to conventional analgesics

IASP Classifications: Peripheral Neuropathic and Central Neuropathic Pain

Neuropathic pain
Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system

Peripheral neuropathic pain

Pain arising as a direct consequence of a lesion or disease affecting the peripheral somatosensory system

Central neuropathic pain

Pain arising as a direct consequence of a lesion or disease affecting the central somatosensory system

Loeser JD, Treede RD. The Kyoto Protocol of IASP Basic Pain Terminology. Pain 2008;137:473-477.

Pathophysiology of Neuropathic Pain

Peripheral mechanisms

Peripheral Neuron hyperexcitability

Central mechanisms Loss of inhibitory controls Abnormal Discharges

NeP

Central Neuron hyperexcitability (central sensitization)

Peripheral Mechanism (Ectopic Discharges)

Nerve lesion induces hyperactivity due to changes in ion channel function

Perceived pain

Nerve lesion

Descending modulation

Ascending input

Nociceptive afferent fiber

Spinal cord
Ectopic discharges

Central Mechanism (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

Loss of descending modulation

Ascending input

Nociceptive afferent fiber

Spinal cord

Central Mechanism (Central sensitization)

After nerve injury, increased input to the dorsal horn can induce central sensitization Perceived pain
Nerve lesion
Descending modulation Ascending input

Nociceptive afferent fiber Perceived pain (allodynia) Abnormal discharges induce central sensitization

Tactile stimuli

Descending modulation

Ascending input

Intact tactile fiber

Development of Neuropathic Pain

Etiology Nerve damage due to:
Metabolic Ischemic Hereditary Compression Traumatic Toxic Infectious Immune-related

Pathophysiology

Mechanisms
Spontaneous pain Stimulus-evoked pain

Symptoms

Syndrome
Woolf and Mannion. Lancet 1999;353:1959-64

Neuropathic pain

The Impact of Neuropathic Pain

Neuropathic pain is widely prevalent & generally affects: 6.9% of people with chronic pain1 Up to 24% of people with diabetes2 Up to 50% of people over 50 who recently had herpes zoster2 75% of people over 70 who have had herpes zoster3 Approximately 33% of cancer patients4 Approximately 4.5% of individuals over 30 following back injury5
1. 2. 3. 4. 5. Zussman J, Young L. Clin Interv Aging 2008;3(2):241-250. Gauthier A et al. Epidemiol Infect 2009;137(1):38-47. Khoromi et al. Pain 2007;130(1-2):66-75. Davis MP, Walsh D. Am J Hosp Palliat Care 2004;21(2):137-142. Meyer-Rosberg K et al. Eur J Pain 2001;5(4):379-389.

Signs and Symptoms of Neuropathic Pain

Sign/Symptom Spontaneous symptoms Description (example)

Spontaneous pain1 Dysesthesias2

Parasthesias2 Stimulus-evoked symptoms Allodynia3 Hyperalgesia3 Hyperpathia2

Persistent burning, intermittent shock-like or lancinating pain Abnormal unpleasant sensations e.g. shooting, lancinating, burning Abnormal, not unpleasant sensations e.g. tingling

Painful in response to a non-nociceptive stimulus e.g. warmth, pressure, stroking Increased pain sensitivity e.g. pinprick, cold, heat Delayed, explosive response to any painful stimulus

1. Baron. Clin J Pain. 2000;16:S12-S20. 2. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212. 3. Loeser JD, Treede RD. The Kyoto Protocol of IASP Basic Pain Terminology. Pain 2008;137:473-477

Hyperalgesia & Allodynia

10 8 Hyperalgesia Normal Pain Response Injury Allodynia 4 2
Hyperalgesiaheightened sense of pain to noxious stimuli Allodyniapain resulting from normally painless stimuli

Pain Intensity

0
Stimulus Intensity

Gottschalk A et al. Am Fam Physician. 2001;63:1979-84.

The Inter-Relationship Between Pain, Sleep, and Anxiety / Depression

Pain

Functional impairment
Anxiety & Depression Sleep disturbances

Nicholson and Verma. Pain Med. 2004;5 (suppl. 1):S9-S27

What is the Correlation Between Causes, Muscular pain, Neuro-endocrine (HPA Axis) disorders and Psychological distress
Emotional, Environmental and Genetic Predisposition
Cortex-Limbic System- Hypocampus Thalamus & Hypothalamus Pituitary Adrenal, Thyroid Perception CRH, TRH, GhRH, PRF, GnRH ACTH, TSH, GH, Prolactine, FCH-LH Cortisone, Thyroid,
Prolactine, Estrogen, Progesterone

Neuro-hormonal Disfunction
Sympathetic Dorsal Horn Metabolic Muscle Trauma

PAIN

Nerve in Fibromyalgia
Cortex Mesencefalon Thalamus Hypothalamus

PAG

Pons

NE

DLP

Medulla

RVM 5-HT NE

NG/NC

DLF
STT Spinal Cord DORSAL HORN

Periphery

PAF
(Kanzler et al., 2002)

5-HT Spinal Cord

NE STT

(Kanzler et al., 2002)

DORSAL HORN

Periphery

PAF

NE 5-HT NE 5-HT 2
Glu NMDA AMPA

STT
mu 5-HT1A
GABA A/B

5-HT3 2

mu

PAF

SP NKA

NK1

Dorsal Horn Neuron

Other Dorsal Horn Neurons

GABA InterNeuron

Anterior Horn Neurons

PAIN ASSESSMENT

The 3L Approach to Diagnosis

LISTEN
Patient verbal descriptors, Q&A

LOCATE
Nervous system lesion / dysfunction

LOOK
Sensory abnormalities, pattern recognition

Pain Assessment Scales

Uni-Dimensional Scale
Only measures pain intensity Appropriate for acute pain The most common scale used in outcome assessment (Analgesic efficacy)

Multi-Dimensional Scale
Both intensity (severity) and unpleasantness (affective) Appropriate for chronic pain Research /pathophysiology Should be used in clinical outcome assessment

Verbal Rating Scale (VRS) None, mild, moderate, severe Numeric Rating Scale (NRS) Visual Analog Scale (VAS) Pictorial Scale

McGill Pain Questionnaire (MPQ) The Brief Pain Inventory (BPI) The Memorial Pain Assessment Card

Uni-Dimensional Pain Assessment Scales

Photographic/Numeric Pain Scale

Multi-Dimensional Pain Assessment Scales

Modified McGill Pain Questionnaire

15 Minutes Sensorik Afektif Evaluatif Macam2 IRN INS

71,4% Baik 28,6% Lumayan dan sedang (Meliala, 1999)

Treatment
Relief

General Activity Mood Walking ability

Quicker and easier Well established reliability in cancer, arthritis, and AIDs. Sensory, affective and functional status Useful for treatment response Takes up to 15 min Good choice for patients with progressive disease

Worst Least

Normal work Relation with other people Sleep

Average

Enjoyment of life
Right Now

 Rapid: Sensory and affective Reliable in Cancer patients Validated Pocket

Patient Pain Diary

10

Pain Scale

Dose 0 Morning Afternoon

Dose Evening Bedtime

ID PAIN : Screening tool to help differentiate nociceptive from neuropathic pain

Neuropathic pain screening questionnaire A multicenter study Patients (N = 586) with non-headache chronic pain A second multicenter study (N = 384) evaluated reliability and validity. 89-item questionnaire 6 items ID Pain appeared to accurately indicate the presence of a neuropathic component of pain (c 74,2%)
Portenoy R et al. Curr Med Res Opin. 2006 Aug;22(8):1555-65.

Mark Yes to the following items that describe your pain over the past week and No to the ones that do not.

If patients have more than one painful area, they are to consider the one area that is most relevant to them when answering the ID Pain questions. Scoring was from 1 to 5. If you score 2 or more, you may have nerve pain. Talk to your doctor. Higher scores are more indicative of pain with a neuropathic component

Location: Patient or nurse marks drawing

Intensity: Patient rates the pain. Scale Used:

Quality: Use patints words, e.g. prick, ache, burn, sharp, hot etc. Onset, duration, variations, rhythms (spontaneus or evoked): Manner of expressing pain: (Pain Behaviour) What relieves the pain?

What causes or increases the pain? Effect of pain: (Note decreased function, decreased quality of life)
Accompanying symptoms (eg nausea) Sleep Appetite Physical activity Relation with others (eg irritability)

Emotion (eg anger, suicidal, crying)

Consentration Other

Other comments: Plan:

Past Medical History

1. Medical related problems 2. Problems potentially affect the choice of pain treatments? 3. Prior or current substance abuse history?

Current Medications
1. Dosage and pattern of use 2. Effectiveness 3. Drug tolerance

Physical Examination
The history will often generate a differential diagnosis The physical exam will often lead to the selection of the primary diagnosis, and occasionally a test will help to confirm this diagnosis

1. 2. 3. 4.
5.

Mental status exam (facial expression) Vital signs Inspection (body position, gait, redness, swelling) Palpation & Musculoskeletal exam (atrophy, location tenderness to pressure, mass, ) Neurologic Examination (Sensory, Motor, Autonomic)

NEUROLOGIC EXAMINATION
Possibility :
spinal cord compression, nerve root lesions peripheral nerve lesions

Sensory Exam.:
numbness, allodinia, hyperalgesia

Motoric: fracture? Deep tendon reflexes Sacral Reflexes

Diagnostic Testing
Ex.: Diagnostic Test For Low Back Pain

Modality

Accuracy % Agree with Surgery

Sensitivity

Specivity

Large of Estimates 0.80 0.82

Clinical Exam

46-76

Radiography
Myelography CT or MRI

34
71-91 70-100

0.67-0.95 0.80-0.95

0.76-0.95 0.68-0.95

Discography
ENMG

30
78

0.83
0.66-0.72

0.63-0.78
-

Bone scans Somato-sensory evoked potential testing (SSEP) Quantitative Sensory Testing (QST)

Psychological Evaluation
1. 2. 3. 4. 5. 6. 7. 8. Mood disorder (50% chronic pain) Somatization Secondary gain Sleep and appetite disturbance Loss of energy and libido Impaired concentration Suicidal ideation Impact of the pain on the patient
day-to-day activities work & finances personal relationships recreational pursuits

CONCLUSIONS

You are the only one who knows how much pain you are feeling All patients require pain assessment it is as essential as the other vital signs!
(Helen Greene)

If You Dont Measure It, You Cant Improve It

(Field et al, 1997)