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(Pathophysiology and Etiology)

Nuzirwan Acang

Bagian Ilmu Penyakit Dalam Fakultas Kedokteran

Universitas Andalas Padang

Pain as an unpleasant sensory and

emotional experience which we primarily
associate with tissue damage or describe in
terms of such damage, or both.
(The International Association for the Study
of Pain = IASP)
 This definition recognizes that pain is a
perception and not a sensation.

An estimated 6.6 million people from around

the world die from cancer each year.
Pain can occur at any point during the course
of the illness
The prevalence of pain
- At the time of cancer diagnosis : 50 %
- At advanced stages
: 75%
- In cancer survivors to be
: 33%
- Approximately 25% of those in nursing

After curative treatment

: 33%
 Under anticancer treatment
: 59%
 Advanced/metastatic/terminal disease
: 64%
 Prevalence of pain was >50% in all cancer types
 Highest prevalence in head/neck cancer patients
: 51% to 88%).

(Annals of Oncology. 2007;18(9):1437-1449.)

Type of cancer and prevalence of pain:

52 %
45 %
85 %
80 %
40 %
Genitourinary tract (male)
75 %
Genitourinary tract (woman)
70 %
20 %
Oxford Textbook of Palliative Care, 2005

Unrelieved severe pain may associated with:

Disturbed sleep
Reduced appetite
Irritability and depression

69% of severe cancer pain patient to cause

consideration of suicide.
(Wisconsin 1985)

Nociceptive pain: Ongoing tissue injury in

somatic structures
Neuropathic pain: Aberrant somatosensory
Visceral pain: Damage of visceral structures

Nocious Stimuli
mechanical thermal chemical
Tissue damage
Release of mediators
Hydrogen and potassium ions,
neurotransmitters, kinins,
Stimulation of nociceptors
Transmission to CNS
via afferent pathways


Disease itself :
- localized
- Metastese
Cancer Treatment
- Surgery
- Radiotherapy
- Khemotherapy
- Hormonal therapy
Noncancer pain condition
- Low back pain
- Arthritis

Tumor expansion can cause pressure on

surrounding organs.
Proteolytic enzymes produced by tumor cells can
damage sensory and sympathetic nerve fibers
Tumors secrete inflammatory and
prohyperalgesic mediators.
Tumor infiltration in nerve plexuses and damage
to nerve tissue can cause neuropathic pain.
Metastatic spread of cancer to bone
Stretching of hollow viscera, distortion of the
capsule of solid organs, inflammation of the
mucosa, and ischemia or necrosis activate
visceral nociceptors, resulting in visceral pain.

Adverse effects of treatment :

- Joint pain following chemotherapy and hormonal
- Painful mucositis due to radiotherapy and
chemotherapy with certain agents.
- Neuropathic pain : postradiation plexopathies,
peripheral polyneuropathy after chemotherapy
- Opioid-induced hyperalgesia
Surgical interventions nerve damage and chronic
postoperative pain.
Procedures related to cancer pain ; biopsies, blood
draws, lumbar punctures, laser treatments

Painful peripheral neuropathy from

chemotherapeutic agents :
vincristine, platinum, taxanes, thalidomide,
bortezomib, and other agents; radiation-induced
Damage of tissue :
- Radiation-induced brachial plexopathy
- Postradiation pelvic pain syndrome
- Postsurgical pain syndromes from
mastectomy, amputation, and thoracotomy.

Acute Pain
A. Due to procedures and therapies

- Acute pain associated with diagnostic

Lumbar puncture headache
Bone marrow biopsy
Lumbar puncture, Venepuncture
Paracentesis, Thoracentes

- Acute pain associated with analgesic techniques

Spinal opioid hyperalgesia syndrome
Acute pain after Strontium-89 therapy of
metastatic bone pain

- Acute pain associated with other

therapeutic procedures
Tumour embolisation
Nephrostomy insertion

B. Acute pain associated with chemotherapy

Pain from intravenous or intra-arterial

Intraperitoneal chemotherapy
Headache due to intrathecal chemotherapy
Painful oropharyngeal mucositis
Painful peripheral neuropathy

C. Acute pain associated with hormonal


Painful gynaecomastia
Luteinising hormone-releasing factor tumour
flare in prostate cancer
Hormone-induced acute pain flare in breast

D. Acute pain associated with immunotherapy

Arthralgia and myalgia from interferon and


E. Acute pain associated with radiation therapy

Painful oropharyngeal mucositis

Acute radiation enteritis and protocolitis

Multifocal or generalised pain (focal metastases

or marrow expansion)
Base of skull metastases
 Pain syndromes of the bony pelvis and hip
 Tumour invasion of joint, or soft tissue, or

Paraneoplastic pain syndromes

Hypertrophic osteoarthropathy
Tumour-related gynaecomastia

Neoplastic involvement of viscera

Hepatic distension syndrome

Rostral retroperitoneal syndrome
Chronic intestinal obstruction and peritoneal
Chronic ureteral obstruction

Process of the pain disease

Acute pain + insufficient pain therapy

Collapse of the body's pain defenses
Central sensitization
Pain memory
Pain disease
Sandkhler, J.: Preventing Pain Memory. MMW 2002; Special
edition 2


Adapted from Mundy G. Nature reviews cancer 2. 584593. 2002

Other somatic symptoms (chronic cough,

nausea, hiccup)
Knowledge and understanding of the patient
Feelings of frustrations, angry and
Social factors (financial, partner, children)
Existential problems
Cultural factors

Pain is a common symptom of cancer, consist of

acute and chronic
Delineate type of cancer: nociceptive,
neuropathic, visceral
Local tumors cause spinal and supraspinal
Metastatic/spread of cancer produced Nociceptive
and visceral pain
Different tumors cause different pain reactivity