Pain Management
Pain is a subjective, unpleasant, sensory, and emotional experience associated with
actual or potential tissue damage or described in terms of such damage.
• Classification
Acute vs. Chronic pain
Nociceptive pain vs. Neuropathic pain
Cancer pain vs. Non-cancer pain
-Nociceptive pain: results from stimulating a normal nerve. Nociception in general
means detection of noxious stimuli by specialized peripheral nerve endings
(nociceptors); this involves the activation of these receptors by external stimuli
(mechanical, thermal or chemical).
These receptors are found in both somatic and visceral structures, once they are directly
stimulated by an external stimulus>> release of bradykinin, prostaglandins, histamine,
interleukins, TNF alpha and other mediators which sensitize and/or activate nociceptors
>>transmission of action potentials via C & B nerve fibers from the site of noxious
stimulus to the dorsal horn of spinal cord which then ascend to higher centers>> the
thalamus may act as a relay station and pass the impulses to central structures where
pain is processed further >> sensation of pain.
-Neuropathic pain: primary lesion dysfunction of the nervous system (peripheral or
central). With neuropathic pain, the nerve fibers themselves might be damaged,
dysfunctional or injured, and these damaged nerve fibers send incorrect signals to other
pain centers. In this type, pain usually is NOT in proportion with the amount of injury,
i.e. there is some sort of dissociation between the severity of pain and the amount of
injury (there may be exaggerated painful responses to normally noxious stimuli
{hyperalgesia} or painful responses to normally nonnoxious stimuli {allodynia}).
-It can be associated with motor, sensory or autonomic dysfunction
-Character of pain as described by the patient: burning, shooting, tingling, shock-like,
etc...
-Opioids alone cannot control such type of pain, so adjuvant analgesics (Coanalgesics)
are usually needed.
**Nociceptive pain is classified into 2 types:
1- Somatic pain: arising from skin, muscles, joints, bone or connective tissue.
>>Localized, aching and throbbing in nature
2- Visceral pain: arising from internal organs (pleura, peritoneum, GIT, etc…).
>>Usually difficult to describe and localize, vague, diffuse and can be colicky in
some cases.
**Opioids play a major role in the management of nociceptive pain (keeping in
mind that opioids work even better on visceral pain than somatic pain).
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Neuropathic Symptoms:
-Paraesthesia: Tingling or pins and needles, spontaneous or provoked, not unduly
unpleasant or painful.
-Dysaesthesia: unpleasant paraesthesia.
-Hypoaesthesia: reduced sensation to a normal stimulus
-Hyperesthesia: increased sensitivity to a stimulus.
-Allodynia: painful sensation resulting from a non-painful stimulus.
-Hyperalgesia: increased sensitivity to a painful stimulus.
-Analgesia: numbness or loss of sensation.
**Pain is NOT only physical; it can be social, psychological or even spiritual.
This concept is called Total Pain. These 4 components are interrelated with one
another. So pain can affect the patient in one or more of the aforementioned domains.
-Physical pain: physical suffering or distress as due to injury, illness...
-Psychological pain: anxiety, fear, or depression, etc...
-Social pain: e.g. inability to work, loss of job or education, inability to take care of the
family, etc…
-Spiritual pain: Loss of sense of meaning, purpose, values and identity in life, fear of
death, etc…
• Pain Assessment:
It’s an ongoing process. You don’t do it only once.
The method used depends on the patient’s background, age, and ability to
communicate:
-Using words (verbal rating scale, mild/moderate/severe)
-Using numbers (0-10, where zero means nothing and 10 means the worst pain
possible), the most widely method used to assess pain.
-Using lines/ visual analogues
-Using images or faces (especially in children)
-Using scales (e.g. Brief Pain Inventory/BPI that assesses total pain)
• Principles of Pain management:
-When it’s possible, treat the cause/etiology of pain, but never delay pain management
for the sake of treating the underlying cause.
-Clear communication (very essential).
-Education of the pt and family.
-Ongoing assessment.
-Interdisciplinary care.
**The earlier the control of pain, the less severe it can get >> prevention of irreversible
consequences.
**there is NO role for Placebo in the treatment of pain in clinical practice. It’s unethical.
• Pharmacological Interventions:
-Opioids: work mainly on the CNS (cerebral cortex particularly).
-Nonopioids: such as steroids and NSAIDS, work on the peripheral nerve endings.
-Adjuvants
WHO 3-Step Ladder:
We choose the proper analgesic(s) according to the severity of pain, so it’s not really a
step-up approach. (e.g., if mild pain>> start with step 1, if severe pain such as cancer
pain >> start with step 3).
Keep in mind that adjuvants can be used at ANY step and are not only limited to severe
cases.
Step 1- Mild (pain rating of 1-3): non-opioids such as Acetaminophen, NSAIDS, or
Aspirin+ adjuvants.
Examples of NSAIDS (Ibuprofen, Diclofenac, Naproxen, Indomethacin, Celecoxib,
Piroxicam), they are good painkillers but may not work in patients with severe pain.
Step 2- Moderate (pain rating of 4-6): weak opioids such as A/Codeine (trade name is
Revacod, it’s a combination of 10mg codeine and 500mg Acetaminophen), Tramadol, or
A/Oxycodone (A stands for Acetaminophen) + adjuvants.
Note: Oxycodone is a strong opioid, however, when it is combined with Acetaminophen,
its dose will be reduced so it can be considered as a weak-moderate opioid. Be careful
that you can NOT give your patient more than 8 tabs of Revacod per day so as not to
exceed the maximum allowed dose of Acetaminophen (4g/day).
Step 3-Severe (pain rating of 7-10): strong opioids such as Morphine, Fentanyl,
Methadone, Hydromorphone, Oxymorphone, or Oxycodone + Adjuvants.
-This ladder is used in a different manner in patients with cancer pain.
-What can cause cancer pain?
It results either from the tumor itself (Obstruction, direct invasion, compression, etc...)
or from treatment (chemotherapy, radiotherapy or surgery).
*In case of cancer pain, you are allowed to give these patients opioids for 10 days
-Non-cancer pain (CA pts can also have this type of pain in addition to cancer pain): co-
morbidities such as diabetic neuropathy or diabetic foot, OA, RA, disc pain, etc...
*For non-cancer pain, you are allowed to give the patient opioids for 3 days only.
• Nonopioids:
Acetaminophen
-Start with it in mild pain.
-Duration of action: 4-6 hrs
-Has analgesic and antipyretic activity but little anti-inflammatory action.
-What are the serious problems associated with acetaminophen? It’s highly hepatotoxic
on overdose.
-What dose can cause hepatotoxicity in a NORMALLY functioning liver?
At least 20g/day (40 tabs)
-In patients with cirrhosis or liver damage or in alcoholics, 3-4g/day of Acetaminophen
can cause liver toxicity.
-What’s the maximum dose that can be prescribed to a patient with normal liver
function who’s NOT an elderly? 4g/day (8 tabs/day, 500mg*2 q 6hrs)
-If you give a patient the maximum allowed dose of Acetaminophen and still s/he has
pain, what would be the best option?
Add one of the NSAIDS such as Ibuprofen or switch to other analgesics.
NSAIDS
-The Maximum allowed dose of Ibuprofen is 2400mg/day (800mg Q 8hrs since the t ½
of Ibuprofen is 6-8 hrs)
-Each agent has a ceiling dose.
-It comes in different doses: 200/400/600/800 mg.
**Adverse effects of NSAIDS:
-GI symptoms: dyspepsia, nausea, abd pain. More serious: Gastritis/ GI ulcer/ GI
bleeding. Use smaller doses if GI intolerance develops.
-Nephrotoxicity.
-Na and water retention which can exacerbate CHF and HTN
-Bronchospasm (can cause exacerbations in pts with asthma)
-Can affect the action of other medications.
• Opioids:
**Opioid receptors types: Mu, kappa and delta. All of them are responsible for the
analgesic effect of opioids through different mechanisms of action.
Mu receptors can cause respiratory depression in overdose.
Endogenous opioids bind to these receptors (e.g. Endorphins, enkephalins,
endomorphins, nociceptin, and dynorphins).
-In general, opioids are conjugated in the liver and excreted via the kidney. They follow a
1st order kinetic reaction.
-Note: If the pt has hepatic or renal disease that impairs the renal clearance of drugs,
you need to adjust the dose of opioids; you either reduce the dose or prolong the dosing
intervals.
**Opioids themselves don’t further damage the kidney or liver in those pts, but it’s their
metabolism that will be affected and may lead to toxicity.
Morphine
-Naturally occurring opioid, 1st line for severe pain.
-Cheap and very effective.
-Acts both centrally and peripherally. It’s also well-absorbed.
-T ½ of morphine is 3-4 hrs
- 4-5 half lives are needed to reach the steady state for ORAL morphine.
- Routes of administration
o Oral: 30-60 mins to reach the Cmax (peak).
o SC: 20-30 mins to reach the Cmax.
o IV: around 6 mins to reach the Cmax.
o Rectally
o IM > very painful, not recommended.
**Breakthrough dose:
It’s the rescue (immediate-release) dose of opioids that is given when the patient
requires opioids for sporadic worsening of pain in addition to the regularly prescribed
dose.
**Any patient who is on opioids should be given 3 prescriptions:
1. Baseline morphine: e.g. 10 mg q12 or 8 hrs (continuous dose).
2. Breakthrough medication, PRN/as needed dose. (10% of the daily dose, if daily dose
is 20 mg, the breakthrough dose is 2 mg)
3. Laxatives to prevent constipation.
Codeine
Formulations: syrup (it’s a good antitussive, used in the past in the treatment of cough)
or tablets (for mild-moderate pain, it’s a weak analgesic).Also, it has been used to treat
diarrhea since it slows the gut (that’s why one of its side effects is constipation)
Oxycodone
-Semisynthetic opioid, given orally, stronger than morphine but more expensive.
- 1 mg of oxycodone equals 1.5 mg of morphine in terms of effectiveness. It’s the 2nd
line agent after morphine.
-Advantages: in patients with hepatic or renal failure and elderly (1st line in such cases
instead of morphine)
Hydromorphone
Stronger than morphine and oxycodone (5-10 times stronger depending on the route of
administration).
Methadone
-Has a variable t ½, used by experts only.
-Long acting but differs from morphine.
-Its half life is unpredictable and needs to be monitored very carefully.
Pethidine (Meperidine)
It is not a good choice for chronic pain mx, it’s usually used in the setting of acute pain
(e.g.For Post op pain in 1 or 2 doses only), but for disc pain or CA pain it shouldn’t be
used since it’s very toxic (may precipitate myoclonus, seizures and tremors) and not very
effective, also has a high addicting potential.
Fentanyl:
-Very Strong but very short acting (short t ½).
-No oral formulations.
-3 formulations:
o Submucosal: Sprays (intranasal), sublingual or lollipop (in breakthrough pain)
o IV: for anesthesia in operations.
o Transdermal patch: this formulation is long acting, t ½ of 48-72 hrs. Usually used
for chronic pain requiring opioid analgesics.
25 micrograms of Fentanyl every hr are equivalent to 50-60 mg of oral morphine
per day. In other words, the Fentanyl transdermal patch is equivalent to a high-dose oral
morphine.
• Oral opioid dosing:
-Immediate-release: used initially, given q 4hrs, increase dose by 25-50% in cases of
persisting mild-moderate pain, and increase it by 100% in cases of severe pain.
-Extended-release: Cmax and t ½ differ (t ½ is longer), more time is needed to be
cleared from the body, given 2-3 times per day (q 8 or 12 hrs)>> better compliance.
Useful as long-term mx, not for rapid titration.
>>Special situations where long-acting (extended-release) opioids are not a good choice:
* For acute, severe pain when you need to rapidly titrate the dose up, you should use
the rapid acting opioids only since you cannot adjust the dose with the extended-
release formulations.
*If a pt has a feeding tube, you can’t give him long acting opioids, because once you
break the long-acting tab, it becomes short acting (immediate release), so these pts are
given frequent doses of rapid acting opioids. In this case you may use a transdermal
patch or immediate-release morphine.
• IV opioid dosing:
- In opioid-naïve patients, start with a low dose (2-3 mg IV bolus) and then taper
-If the patient is already on opioids, give them the IV equivalent of their oral dose (e.g.
5mg morphine IV, 1.5mg Hydromorphone IV, 60mg codeine are all equivalent to 15
mg oral morphine).
Adverse effects of opioids:
**Common:
-Constipation: in 90-100% of cases, pts won’t become tolerant to it, that’s why all pts
should be maintained on laxatives.
-Dry mouth
-Nausea and vomiting: pt will develop tolerance in 3-7 days; if severe enough, you can
give the pt an antiemetic for 1 week.
-Sedation: pt will develop tolerance in 3-7 days.
-Sweating
**Uncommon: there is no tolerance, switch to another opioid if any develops
-Psychomimetic effects: Hallucination, delirium, myoclonus, seizures.
-urine retention
-Respiratory depression
-Pruritus
**Allergy: Bronchospasm, urticaria or anaphylactic reaction.
Issues with opioids:
-Equi-analgesic doses:
*The dose of opioid equivalent to a given dose of morphine as a reference.
*Doses equivalent to 15mg of oral morphine: 4mg Hydromorphone, 10mg Oxycodone,
15mg Hydrocodone, and 100mg Codeine.
-Cross-tolerance:
*This means that different opioids can induce tolerance to each other, since they act on
the same receptors.
*In rotating opioids (periodically changing the opioid for long-term Rx), give 70% of the
opioid dose as you switch, since the receptors are already occupied with the previous
agent.
A few concepts that are often used interchangeably:
▪ Addiction: an uncontrollable or overwhelming cravings to use a drug despite its
harmful consequences, this requires psychological detrimental effect of opioids
on the pt, psychological dependence, loss of control and loss of interest in
withdrawing it. Unlike physical dependence, it’s abnormal and classified as a
disease.
▪ Tolerance: a physiological state where the effectiveness of a drug has diminished
due to chronic administration. This means that more of the drug will be required
to achieve the same effect in the future.
▪ Physical dependence: a physical condition in which the body has adapted to the
presence of a drug, if an individual with drug dependence stops taking that drug
suddenly, that person will experience predictable and measurable symptoms,
known as withdrawal syndrome. That’s why the dose has to be tapered gradually.
• Adjuvants/ Coanalgesics:
-Given to enhance the effect of concurrent analgesics.
-Can be used in all steps of pain mx.
-Benefits: reduce other analgesics’ dose, enhance their effect, and are useful in cases of
incomplete response to opioids.
Examples:
o Antidepressants (Amitriptyline, Imipramine, Duloxetine…)
o Anticonvulsants (Gabapentin, Carbamazepine, Valproic acid, Pregabalin)
o NMDA receptors antagonists
o Others: acetaminophen, NSAIDS, Steroids
Indications: Neuropathic pain, bone pain, muscle spasm, liver capsule pain, anorectal
pain, bowel and bladder spasm.
-Opioids alone usually are not enough in such cases. But remember that every individual
is different from the next.
-Neuropathic pain is the most difficult to treat.
-Steroids are very effective when combined with opioids.
Dexamethasone is the agent of choice in most cases, this combination is usually used for
bone pain or liver capsule pain (where the liver is enlarged due to mets or inflammation)
as well as in bowel obstruction. But be careful of its adverse effects on the long term.
NOTE: In non-cancer neuropathic pain, you may start with an adjuvant agent alone
**For Bone pain: NSAIDS, steroids, bisphosphonates or calcitonin are usually
recommended. BUT if bone pain is due to mets, we start with opioids.
**Anticholinergics are good coanalgesics for pts with anorectal pain or bladder spasm.
** Muscle relaxants: in muscle pain
• Nonpharmacologic pain management
-Medical and Surgical treatment.
-By treating the underlying cause
-Neurostimulation
-Tense acupuncture
-Anesthesia: local or regional blocks
-POT: physical & occupational therapy
-Psychological approaches
-Complementary therapy such as music
-Massage
Barriers in pain management:
-Physician factors:
Lack of knowledge, skills or attitude
Fear of opioids due to addiction, tolerance, adverse reactions or death
Regulatory oversight
-Patient factors:
Fear of opioids and Cultural beliefs (some cultures encourage tolerating pain)
