PAIN

MANAGEMENT

Supported by EPEC
Pain pathophysiology

Acute pain
identified event, resolves days-weeks,
usually nociceptive

Chronic pain
cause often not easily identified, multifactorial
indeterminate duration
nociceptive and/or neuropathic
 Process of nocyception
BRAIN
CORTEX
PERCEPTION

MODULATION
Thalamus

WDR

TRANSMISION
DRG
TRANSDUCTION
Nociceptive pain…

Direct stimulation of intact nociceptors

Transmission along normal nerves

Sharp, aching, throbbing

somatic
easy to describe, localize
visceral
difficult to describe, localize
…Nociceptive pain

Tissue injury apparent

Management
opioids
adjuvants
 Peripheral mechanisms
DRG

Nerve injury
Neurogenic inflammation

Inward stimulation

Genes expression

Novel receptors and ion channels

„ectopic nerve pace-makers”
pathologic sodium channels
 Nocyceptor Peripheral mechanisms
ANS neuron
C
B A

Spontaneus impulses
in „ectopic nerve pace-makers”
Primary pain
Pathologic connections A and C

Secondary pain, alodynia

Pathologic connections of C fibers
and eferent adrenergic
Proliferation of B fibers to DRG
Sympathetic maintained pain

Emerging of new fibers- neuroma

Yaksh T. The Journal of Pain 2006
Devor M. The Journal of Pain 2006
Central mechanisms

Morphotic changes in DR.

Pathologic connections
between laminas II and III.
Alodynia

Damage to ascending
inhibitory pathways.

Change in calcium channels

density in laminas I and II.
Central sensitisation
Neuropathic pain…

Disorder peripheral or central nerves

Compression, transection, infiltration,

ischaemia, metabolic injury

Varied types
peripheral, deafferentation, complex regional
syndromes
…Neuropathic pain

Pain may exceed observable injury

Described as burning, tingling, shooting,

stabbing, electrical

Management
opioids
adjuvants / coanalgesics often required
Breakthrough pain- definition

Transient, exacerbating flares of pain,

spontaneous or caused by predictable
or unpredictable situation, emerging even when
an effective basal pain controll is achieved.
Breakthrough pain

Acute onset
Moderate or severe intensity
Short time of duration- approx. 30 min. (1-240)
Relatively small number of episodes- approx. 4
(1-14)
Pain management

Don’t delay for investigations or disease

treatment

Unmanaged pain nervous system changes

permanent damage amplify pain

Treat underlying cause

(eg. Radiation for a neoplasm)
 NRS Numeric Rating Scale

1. Pain intensity in numeric scale from 0 to 10.

2. In this scale 0 means „no pain”, and 10 –

„worst imaginable pain”
 BASIC RULES
of alleviating and control
of chronic and cancer pain
[ by WHO i IASP ]

Drugs should be administered orally.

Drugs should be administered on regular

manner, „by the clock”.

WHO 3-step Analgesic Ladder.

Individual dosing.

Watch out for symptoms.

 WHO 3-step Ladder
____________________
MORPHINE 3 severe
Buprenorphine
Fentanyl
Oxycodone
Methadon, Hydromorphone,
+/- Adjuvants

__________ Codeine 2 moderate

TRAMADOL
Dihydrocodeine, Hydrocodone
+/- Adjuvants
__________________

___________
ASA 1 mild
PARACETAMOL (Acetaminophen)
NSAIDs
+/- Adjuvants
Paracetamol (Acetaminophen)

Step 1 analgesic, coanalgesic

Site, mechanism of action unknown

minimal anti-inflammatory effect

Hepatic toxicity if > 4g/24 hours

increased risk
hepatic disease, heavy alcohol use
NSAIDs…

Step 1 analgesic, coanalgesic

Inhibit cyclo-oxygenase (COX)

vary in COX-2 selectivity

All have analgesic ceiling effects

effective for bone, inflammatory pain
…NSAIDs

Highest incidence of adverse events

Gastropathy
gastric cytoprotection
COX-2 selective inhibitors
NSAIDs adverse effects

Renal insufficiency
maintain adequate hydration
COX-2 selective inhibitors

Inhibition of platelet aggregation

assess for coagulopathy
Opioid pharmacology…

Conjugated in liver

Excreted via kidney (90-95 %)

First-order kinetics
Opioid pharmacology…

Cmax after
po = 1h
S.C., IM = 30min
IV = 6min

Half-life at steady state

po / pr / SC / IM / IV = 3-4h
…Opioid pharmacology

Steady state after 4-5 half-lives

steady state after 1 day (24 hours)

Duration of effect of „immediate-release”

formulations (except methadone)
3-5 hours po / pr
shorter with parenteral bolus
Routine oral dosing
immediate-release preparations
Codeine, hydrocodone, morphine,
hydromorphone, oxycodone
Dose q 4h
Adjust dose daily
Mild / moderate pain 25-50 %
Severe / uncontrolled pain 50-100 %
Adjust more quickly for severe / uncontrolled pain
Routine oral dosing
extended-release preparations
Improve compliance, adherence

Dose q 8, 12, 24h (product specific)

don’t crush or chew tablets
may flush time-release granules down feeding tubes

Adjust dose q 2-4 days (once steady state

reached)
Routine oral dosing
long half-life opioids
Dose interval for methadone is variable (q 6h
or q 8h usually adequate)

Adjust methadone dose q 4-7 days

Breaktrough dosing

Use immediate-release opioids

5-15 % of 24-h dose
offer after Cmax reached
po / pr = q 1h
SC / IM = q 30min
IV = q 10-15min

Do NOT use extended-release opioids

Clearence concerns

Conjugated by liver

90-95 % excreted in urine

Dehydration, renal failure, severe hepatic failure

dosing interval, dosage size
if oliguria or anuria
STOP routine dosing of morphine
use ONLY prn
Alternative routes of administration

Enteral feeding tubes

Transmucosal
Rectal
Transdermal
Parenteral
Intraspinal
Transdermal patch

Fentanyl, buprenorphine
peak effect after aplication = 24 hours
patch lasts 48-72 hours
ensure adherence to skin
Parenteral

SC, IV, IM
bolus dosing q 3-4h
continuous infusion
easier to administer
more even pain control
Opioid adverse effects

Common Uncommon
Constipation Bad dreams / hallucinations
Dry mouth Dysphoria / delirium
Nausea / vomiting Myoclonus / seizures
Sedation Pruritus / urticaria
Sweats Respiratory depression
Urinary retention
Constipation…

Common to all opioids

Opioid effect on CNS, spinal cord,

myenteric plexus of gut

Easier to prevent than treat

Constipation…

Prokonetic agent
metoclopramide

Osmotic laxative
lactulose, sorbitol

Other measures
…Constipation

Diet usually insufficient

Bulk forming agents not recommended

Stimulant laxative
senna, bisacodyl, glycerine, casanthranol etc

Combine with a stool softener

senna + docusate sodium
Nausea / vomiting…

Onset with start of opioids

tolerance develops within days

Prevent or treat with dopamine-blocking

antiemetics
prochlorperazine, 10mg q 6h
haloperidol, 1mg q 6h
metoclopramide, 10mg q 6h
…Nausea / vomiting

Other antiemetics may also be effective

Alternative opioid if refractory

Sedation…

Onset with start of opioids

distinguish from exhaustion due to pain
tolerance develops within days

Complex in advanced disease

…Sedation

If persistent, alternative opioid or route

of administration

Psychostimulants may be useful

methylphenidate, 5mg q am and q noon, titrate
Respiratory depression…

Opioid effects differ for patients treated for pain

pain is potent stimulus to breathe
loss of consciousness precedes respiratory
depression
pharmacologic tolerance rapid
…Respiratory depression

Management
identify, treat contributing causes
reduce opioid dose
observe

if unstable vital signs

naloxone, 0,1-0,2mg IV q 1-2min
Adjuvant analgesics…

Medications that suplement primary analgesics

may themselves be primary analgesics
use at any step of WHO ladder
…Adjuvant analgesics

Tricyclic antidepressants
amitryptyline, desipramine
Anticonvulsants
gabapentin, carbamazepine, valproic acid
Corticosteroids
dexamethasone
Bisphosphonates
alendronic acid, risendronic acid, clodronic acid,
pamindronic acid