Pain management

International Association for the
Study of Pain
 Pain is an unpleasant sensory and emotional
experience associated with actual or potential
tissue damage, or described in terms of such
damage

What is “Total Pain”?
Total
Pain
Physical
Other symptoms
Adverse Rx effects
Insomnia/Chronic fatigue
Psychological
Anger
Disfigurement
Fear of pain/death
Helplessness
Social
Family/Finance worries
Loss of job/income
Loss of role
Abandonment/Isolation
Spiritual
Why me?
Anger at God
What is the point?
Guilt

Pain In Oncology
 Tumor related: 60-80% of patients
 Therapy induced: 20-25% of patients
• Chemotherapy
• Radiotherapy
• Surgery
 Others: 3-10%
DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology 10th edition

FACT SHEET
 Moderate to severe pain : 1/3rd patients on
active therapy
 Advanced disease : 60% to 90% patients
 Most common cause : Pain related to direct
tumour involvement
 Most common type : Bone pain
 Chronic pain is also prevalent in cancer
survivors, with prevalence rates ranging from
5% to 40%

Types of pain
Pain
Nociceptive
Somatic Visceral
Non
Nociceptive
Neuropathic Psychogenic
Perez and brady’s principles and practice of radiation oncology (sixth edition)

Nociceptive pain
 Refers to the nervous system response that is
proportionate to the tissue damage
SOMATIC
Well-localized sharp,
stabbing (knifelike), and
achy pain as
a response to skin, muscle,
and connective tissue
damage
VISCERAL
Non localized, cramping,
dull ache

Non Nociceptive pain
 Neuropathic pain : Abnormal pain processing by the
peripheral or central nervous system.
 Patients may complain of burning, shooting, tingling, or
numbness, which generally occurs along a nerve
distribution
 Psychogenic causes : Depression and anxiety may
exacerbate the perception of painful stimuli.

Temporal Aspects of Pain
 Acute pain : A well-defined temporal pattern of pain
onset
 Chronic pain : Pain that persists for more than 3
months
 Baseline pain : Average pain intensity experienced for
12 or more hours during a 24-hour period.
 Breakthrough pain : Transient increase in pain to
greater than baseline pain

MEASUREMENT OF PAIN
 Brief Pain Inventory
 Visual Analogue Scale
 McGill Pain Questionnaire
 Memorial Symptom Assessment Scale
 Functional Assessment of Cancer Therapy – General
(FACT-G)
 European Organization for Research and Treatment of
Cancer Quality of Life Questionnaire-C30
 Edmonton Symptom Assessment Scale

PAIN ASSESSMENT PRINCIPLES
 Screen for pain at each contact
 Pain intensity must be quantified and qualified
 Pain assessment must be performed if new or worsening
pain is present and regularly performed for persisting pain
 Note patient reporting of quality of pain, breakthrough
pain, treatment used, satisfaction with pain relief
 Evaluate patient for risk factors for opioid abuse
NCCN Guidelines Version 2.2016 Adult Cancer Pain

CLINICAL ASSESSMENT OF PAIN
 Believe the patient’s complaint of pain
 Careful history
 Patient’s psychological state
 Careful medical and neurologic examinations
 Appropriate diagnostic studies
 Treat pain to facilitate appropriate workup
 Reassess response

GOALS
 Optimize Analgesia
 Optimize activities of daily living
 Minimize adverse effects
 Avoid aberrant drug taking
NCCN Guidelines Version 2.2016 Adult Cancer Pain

Management
Medical Interventional
Complementary
Therapies
Specific
Scenarios

MEDICAL MANAGEMENT
 Analgesic Drug Therapies
 Opioid Analgesics
 Non opioid analgesics
 Adjuvant therapies
 Hallmarks
 Titration to effective pain relief
 Individualization of treatment

PRINCIPLES FOR EFFECTIVE
PHARMACOLOGIC TREATMENTS
 By mouth
 By the clock
 By ladder
 For the individual
 Attention to detail
WHO Cancer Pain Relief Guidelines

Non Opioids
NSAIDs
Nonselective COX
inhibitors
Analgesic
Antipyretics with
poor anti
inflammatory action
Preferential COX 2
inhibitors
Selective COX 2
inhibitors
Essentials of Medical Pharmacology 7th Edition KD Tripathi

Analgesic Antipyretics with poor anti
inflammatory action
 PARACETAMOL
 OTC
 Dose : 325 – 650mg 3-5 times/day
 Aspirin + PCM : Additive
 Ceiling effect : Aspirin + PCM = 1000mg
 No ceiling effect with opioids

Non Selective COX inhibitors
 Aspirin :
 Dose : 300mg – 600mg 6-8 hourly
 T1/2 : dose dependent ; analgesic : 3-5 hours
 S/E : Nausea, epigastric distress
 Ibuprofen : 400mg 6-8hourly
 Mephenamic Acid : Strong inflammatory action
Dose : 250-500mg TDS

COX-2 inhibitors
 Less gastrointestinal (GI) toxicity and without
affecting platelet function
 Nimesulide : Preferential COX2 inhibitor
 Celecoxib : Selective COX2 inhibitor

Opioid Analgesics
 Prototype : Morphine
 Mechanism of Action : Interaction with specific opioid
receptors - primary effect centrally
 Opioid responsiveness : Degree of analgesia achieved
during dose escalation to either intolerable side effects
or adequate analgesia

PRINCIPLES OF PRESCRIBING
 In opioid-naive patients : conventional treatment
usually relies on a short-acting, single-entity opioid or
combination product.
 Starting dose : Equivalent to 5 to 15 mg of oral
morphine every 3 to 4 hours
 If pain persists and multiple daily doses are required :
transition to a single-entity, long-acting opioid
formulation

Opioid Dose Escalation
Always increase by a percentage of the present dose based
upon patient’s pain rating and current assessment
Mild pain
1-3/10
25% increase
Moderate pain
4-6/10
25-50% increase Severe pain
7-10/10
50-100% increase

Pharmacokinetics of Opioids
 Onset of pain relief
 Oral opioids 15–30 min
 SC opioids 5–10 min
 IV opioids 1 min
 Duration of pain relief
 Short-acting oral opioids 3–5 hours
 Long-acting oral opioids 8–12 hours
 IV or SC opioids 2–4 hours

Routes of Administration
 Preferred route – oral
 When unable to swallow: SC, Rectal, IV, TD
 Seldom used (only in special situations):
 Sub Lingual (breakthrough pain, fentanyl)
 Intraspinal (epidural or intrathecal)
 Do not use IM

Fentanyl
 Transdermal patches : 12.5 to 100 μg per hour doses
 Changed every 72 hours
 A 12 to 15-hour delay in the onset of analgesia : use
alternate approaches
 Adequate subcutaneous fat should be present
 Transmucosal preparations : breakthrough pain

Other Opioids
 Hydromorphone :
 No differences in analgesia or side effects between
morphine and hydromorphone
 Limited clinical experience and high cost
 Oxycodone :
 5-mg dose : WHO Step 2
 Reduced histamine effect

 Methadone :
 Second-line drug for cancer pain
 Buprenorphine
 Transdermal preparation
 Does not accumulate in patients with renal dysfunction
 Tramadol
 Atypical opioid
 Less side effects as compared to morphine
 WHO step 2
 Dose : 100mg i/v (effect lasts for 4-6 hours)

Side Effects
 Sedation
 Nausea
 Vomiting
 Constipation
 Respiratory depression
 Multifocal myoclonus
 Seizures
DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology 10th
edition

Sedation and drowsiness
 Very common
 Management
 Reduce dose –increase frequency of administration
 Switch to an analgesic with a shorter plasma half-life
 Amphetamine, methylphenidate, caffeine counteract
opioid induced sedative effects.
 It is important to discontinue all other drugs that might
exacerbate the sedative effects of opioid analgesics

Nausea and Vomiting
 Tolerance develops to these side effects with repeated
administration
 Incidence is increased in ambulatory patients
 Switch to alternative opioid analgesics
 Use an antiemetic

Constipation
 Action at multiple sites in the GI tract and in the
spinal cord to produce a decrease in the intestinal
secretions and peristalsis
 Regular bowel regimen
 Cathartics and stool softeners
 Opioid antagonist methylnaltrexone is FDA-approved
for the indication of opioid-induced constipation

Respiratory depression
 Most serious adverse effect
 Act on brain stem respiratory centers to produce, as a
function of dose, increasing respiratory depression to
the point of apnea
 Tolerance develops rapidly with repeated drug
administration.
 Treatment : Naloxone (dose: 0.4 mg per milliliter)

Naloxone
 Competitive antagonist
 No effect on individuals not exposed to opioids
 Dose : 0.4-0.8mg i/v
 Analgesia is gone
 Stimulates respiration
 Sedation less completely reversed
 Max dose : 10mg i/v

Taper drugs slowly
 Sudden cessation of the opioid analgesic produces
withdrawal symptoms
 Agitation, tremors, insomnia, fear, exacerbation of
pain.
 Reinstituting the drug in doses of approximately 25%
of the previous daily dose suppresses these symptoms.

ADJUVANTS
 To enhance opioid analgesia
 Provide analgesia for certain types of pain (e.g.,
Neuropathic pain, bone pain, visceral pain)
 Treat opioid side effects or other symptoms associated
with pain

Bone Pain
 Most common cause of pain in metastatic disease
 Surgical palliative approaches, radiotherapeutic
approaches, hormonal therapies, and bone resorption
inhibitors
 Refractory multifocal pain : strontium-89 and
samarium-153, radium-223
 Bone marrow suppression is the major adverse effect,
with irreversible thrombocytopenia

Neuroablative
Techiques
Cryoanalgesia Radiofrequency
Chemical
neurolysis

Neuroaxial
techiques
Epidural Intrathecal Electrostimulation

Neurosurgical techniques
 Reserved for refractory pain and specific indications
 Thalamotomy
 Deep-brain stimulation

Complementary Therapies
 Acupuncture
 Hypnosis
 Biofeedback
 Massage
 Music therapy
 Mind–body exercises
 Dietary supplementation

Muscle Spasm
 One-time muscle exposures to 10 to 20 Gy or
fractionated doses >55 Gy are associated with
myokymia, pain, and decreased muscle strength and
range of motion
 Treatment regimen includes early physical therapy and
orthopedic exercises and pharmacologic therapy such
as muscle relaxants (e.g., baclofen)

Plexopathy
 Nerve bundles exposed to a one-time dose of 28 Gy, or
fractionated doses totalling 60 Gy
 Treatments involve early physical and occupational
therapy, multimodality pain regimens, neurolytic
procedures

Mucositis and Proctitis
 Debilitating and may result in dose limitations of
radiotherapy
 Mucositis : NSAIDs, topical analgesics, good oral
hygiene, honey, hydrolytic enzymes, zinc, laser
therapy
 Proctitis : NSAIDs, topical steroids, such as
hydrocortisone cream, and the use of sucralfate.

Pain management

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