dr. Ken Wirastuti, MKes, Sp.

S
Bagian Ilmu Penyakit Saraf
Fakultas Kedokteran-Universitas Islam
Sultan Agung
Classification of Neuropathic Pain
 Duration
– Acute neuropathic pain (< 3 months)
– Chronic neuropathic pain(>3 months)
 Location
 Peripheral neuropathic pain
 Central neuropathic pain
 Sympathetically maintained pain
 Describe
 Non-painful stimuli are now painful
 Can be episodic or continuous
 Example: trigeminal neuralgia (light touch)
 Nonsympathetically mediated pain=Peripheral
Neuropathic Pain  is due to damage to a peripheral
nerve without autonomic change (eg, post-herpetic
neuralgia, neuroma formation).

 Central Neuropathic Pain  arises from abnormal central

nervous system (CNS) activity (eg, phantom limb pain,
pain from spinal cord injuries, and post-stroke pain).

 Sympathetically mediated pain  from peripheral nerve

lesion and associated with autonomic changes (eg, complex
regional pain syndrome I and II [reflex sympathetic
dystrophy and causalgia]).
What is Neuropathic Pain?
 Nyeri biasanya bertahan lebih lama dan merupakan proses
input sensorik yang abnormal oleh sistem saraf perifer atau
 Seringkali tidak diketahui penyebabnya dan respon terhadap
terapi standart buruk  lebih sulit diobati
 Dapat berakhir indefinitely dan bahkan meningkat dari waktu
ke waktu
 Mengakibatkan disabilitas berat

Wall PD. Textbook of Pain. 4th ed. 1999; Dworkin RH, et al. Arch of Neuro.
2003;60:1524-1534; Belgrade MJ. Postgraduate Medicine.1999;106(6):127-140.
Neuropathic Orofacial Pain
 Perubahan menetap pada daerah dimana saraf
pertamakali mengalami injuri
 Perubahan tersebut dapat mengakibatkan nyeri yang
berlangsung terus meski telah sembuh
 Sistem saraf dapat mengalami perubahan baik di
perifer muapun di sentral
 Nyeri bisa diprovokasi oleh sentuhan ringan, panas,
dingin (Allodynia, Hyperalgesia)
 Nyeri paroxysmal, nyeri umum, tumpul sampai tajam,
seperti ditusuk, seperti disetrum
 Nyeri kronis yang berasal dari otak, saraf kranialis,
wajah dan leher.
 Dapat diterapi secara efektif jika diagnosa sudah
ditegakkan.
How Neuropathic Pain Happens
 When nerves become damaged or injured, they
stop working properly
 May send the wrong signal to the brain
 Injured nerves might tell the brain that your foot is
experiencing burning pain even when you aren’t
stepping on something hot

 Nerves can be injured or damaged in a number

of ways, including a spinal cord injury or a
medical condition such as diabetes, shingles or
a stroke
Price SA. Pathophysiology: Clinical Concepts of Disease Processes. 5th ed; 1997
Pain Mediators
Cell Damage

Brain
Aa K+ BK

PG

Nociceptor
Spinal cord

HISTAMINE

Mast Cell
Peptides, eg, SUBSTANCE P

SEROTONIN
Aa = arachidonic acid; BK = bradykinin; PG = prostaglandin
Platelet
 Role of Neurotransmitters
Excitatory
 Glutamate, aspartate, ATP
 Mediate afferent synaptic transmission
Inhibitory
 GABA, glycine, norepinephrine, 5-HT, adenosine,
Ach
 Analgesia at spinal and higher levels
 Altered function  hyperalgesia, neuropathic or
chronic pain

GABA = -aminobutyric acid; 5-HT = 5-hydroxytryptamine (serotonin); Ach = acetylcholine

Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional
Anesthesia; 1999:7–9.
 Role of Neuropeptides
Excitatory
 Substance P, neurokinin A
  Ca2+, induce sensitization, hyperalgesia
 Transsynaptic transmitters
Inhibitory
 Somatostatin, enkephalins, endorphins,
dynorphins
 Modulate intracellular cAMP, K+
 Act at , ,  opioid receptors
cAMP = cyclic adenosine monophosphate
Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional
Anesthesia; 1999:7–9.
(Peripheral Afferent Nerves)
Central Sensitization
Peripheral
Sensitization Tissue Injury

  C-fiber output
 Hyperalgesia (1, 2)
 Allodynia
 Activation of NMDA
receptors
Spinal cord
Sensitization
10

8 Hyperalgesia Normal
Pain
Pain Intensity

Response
6 Injury
Allodynia
Hyperalgesia—
4 heightened sense of
pain to noxious stimuli
2 Allodynia—pain
resulting from normally
painless stimuli
0

Stimulus Intensity

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

Hyperalgesia
Primary
 Sensitization of primary neurons   threshold to noxious
stimuli within site of injury
 May include response to innocuous stimuli
  pain from suprathreshold stimuli
 Spontaneous pain
Secondary
 Sensitization of primary neurons in surrounding uninjured areas
 May involve:
– Peripheral sensitization
– Central sensitization

Raja SN, et al. In: Wall PB, Melzack R, eds. Textbook of Pain. 4th ed; 1999:11–57.
 Allodynia
 Pain evoked by innocuous stimuli
 Central sensitization  pain produced
by A fibers1
 Possibly mediated by spinal NMDA
receptors2

1. Woolf CJ. Drugs. 1994;47(suppl 5):1–9.

2. Dolan S, Nolan AM. Neuroreport. 1999;10(3):449–452.
Possible Descriptions of Neuropathic Pain
 Sensations  Signs/Symptoms
 numbness  allodynia: pain from a
 tingling stimulus that does not
 burning normally evoke pain
 thermal
 paresthetic
 mechanical
 paroxysmal
 hyperalgesia:
 lancinating exaggerated response to
 electriclike a normally painful
 raw skin stimulus
 shooting
 deep, dull, bonelike ache
Neuropathic Pain is Different
from Muscle/skeletal Pain
Neuropathic Pain Muscle/skeletal Pain

Chronic pain (months/years) Acute pain (hours or days)

Caused by injury or disease to Caused by injury or inflammation

nerves that affects both the muscles and
joints
Mild to excruciating pain that can Moderate to severe pain that
last indefinitely disappears when the injury heals

Causes extreme sensitivity to Causes sore, achy muscles

touch –simply wearing light
clothing is painful

Sufferers can become depressed Sufferers can become anxious

or socially withdrawn because and distressed but optimistic
they see no relief in sight and may about relief from pain
experience sleep problems
Wall PD. Textbook of Pain. 4th ed; 1999; Jude EB. Clin in Pod Med and Surg.1999;16:81-97;
Price SA. Pathophysiology: Clinical Concepts of Disease Processes. 5th ed; 1997: Goldman L.
Cecil Textbook of Medicine. 21st ed; 2000
Emotional and Social Impact of
Neuropathic Pain
People with neuropathic pain report:
 Difficulty sleeping
 A lack of energy
 Drowsiness
 Difficulty concentrating
 Strained relationships with family and friends
 An inability to work, walk, or even wear
clothes as the contact with their skin can
cause an unbearable burning pain

Meyer-Rosberg K. Euro J of Pain. 2001;5:379-389;

Berger A.. Pain. 2004;5(3):143-9
The most common neuropathic
pain syndromes in the orofacial
 traumatic neuropathy;
 trigeminal neuroma;
 postherpetic neuralgia;
 diabetic neuropathy;
 cancer-related neuropathy;
 neuropathy induced by acquired
immunodeficiency syndrome, or AIDS;