What is pain?

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue
damage

Pain pathway –

Transduction – conversion of a noxious stimuli (chemical, mechanical, or thermal) into electrical energy
 transmission – electrical stimuli sent to the dorsal horn of the spinal cord and synapse at the 2 nd order
neuron  modulation – inhibition vs amplification of signal  perception – conscious awareness of pain
as a culmination of previous processes in the context of the individuals experiences

Classified as nociceptive or pathophysiologic pain

Nociceptive: occurs when the sensory nerves identify tissue damage. Injured tissue releases substances
(such as prostaglandins (PGs), substance P, histamine) which stimulate the nociceptors to send impulses
to the brain that result in feeling pain. Results from injury to the skin, muscles, bones, joints, or
ligaments (somatic pain/musculoskeletal pain)

Pathophysiologic pain: does not result from tissue damage, but from damage or malfunction of the
nervous system. This is commonly referred to as neuropathic pain. Various pain syndromes are
considered pathophysiologic pain, such as fibromyalgia, diabetic neuropathy, chronic headaches, drug
induced toxicities and others

Acute vs chronic pain

Acute pain begins suddenly and usually feels sharp. It is typically nociceptive in nature, such as a
fracture, burn, acute illness, surgery or childbirth. The pain can last just a few moments, or longer and
usually goes away when the cause of the pain has resolved. Acute pain can cause anxiety and physical
symptoms, including sweating and tachycardia. If acute pain goes untreated, it has been shown to
increase the risk for the development of chronic pain.

Chronic pain has been described as pain that persists beyond the normal healing time (or three months),
but for some conditions there is no acute injury. It can persist with a visible injury or when no visible
injury is present, such as osteoarthritis or diabetic neuropathy. OA is a common type of chronic pain
caused by a breakdown in the cartilage that pads the join, which results in stiffness, pain and or swelling.
Chronic pain is divided into cancer pain and non-cancer pain, which have separate treatment guidelines.
Poorly managed chronic pain is miserable and can cause depression and physical symptoms, including
muscle tension and fatigue.

Pain is subjective

Monitor pain level and type or quality (burning, shooting, stabbing, aching) and the time of day that the
pain is better or worse.

Pain scales

Are useful to assess pain severity. Pain is commonly rated using a numeric scale (0-10) or with the visual
analog scale for pediatric patients.

Managing pain
Mild pain (scale 1-3) = step 1, moderate pain (6-4) = step 2, severe pain (7-10) = step 3

Agents
Acetaminophen – reduces pain and fever (antipyretic) but does not provide an anti-inflammatory effect.
The mechanism of action is not well-defined but is thought to involve inhibition of PG synthesis in the
CNS resulting in reduced pain impulse generation

Max 4 gm (q4h dosing)

Tylenol

+ hydrocodone (norco)

+codeine (Tylenol #2,3,4)

+caffeine (Excedrin)

+aspirin/caffeine (Excedrin extra strength)

+caffeine/pyrilamine (midol)

Fiorcet (butalbital/caffeine)

Peds = 10-15 mg/kg q4-6

BBW: severe hepatotoxicity (can require liver transplant or result in death) with doses greater than 4 gm
per day or using multiple products

Warning: severe skin reactions (SJS, TEN) rare

SE: generally well-tolerated with oral admin

Injection – 10 mg/ml

Drug interactions – can be used with warfarin, but if used chronically can increase INR

Alcohol

Antidote = N-acetylcysteine = restores hepatic glutathione administred IV or PO

NSAIDS –

Decrease the formation of PGs which results in decreased inflammation, alleviation of pain and reduced
fever. Cyclooxygenase COX 1 and 2 enzymes catalzye the conversion of arachidonic acid to PGs and
thromboxane A2. Non-selective block the synthesis of both COX enzymes. COX 2 selective block the
synthesis of COX 2 only which decreases GI risk because cox 1 protects the gastric mucosa. Blocking cox
1 decreases the formation of TxA2 which is required for both platelet activation and aggregation. Aspirin
is an irreversible Cox 1 and 2 inhibitor and is an effective antiplatelet agent that provides CV benefit.

Non aspirin BBW:

All prescription NSAIds require a medguide due to these risks.

GI risk: increase risk for serious GI adverse events including ulcer and bleed. Esp elderly, history of GI
bleed, taking systemic steroids, or SSRIs or SNRIs

CV risk: increase the risk of MI and stroke. Avoid use in patients with CV disease or risk factors.

CABG (coronary artery bypass graft) surgery – contraindicated after CABG surgery. Antiplatelet therapy
is recommended.

SE: can decrease renal clearance by reducing blood flow to the glomerulus; additional nephrotoxic
agents or dehydration increases the risk. All nsaids should be used cautiously or avoided in renal failure

Can increase blood pressure – use cautiously in pts with controlled htn and avoid in pts with
uncontrolled htn

Can cause premature closure of the ductus arteriosus which can lead to hf in the baby. Do not use in
third trimester of pregnancy (>30 weeks).

Can cause nausea. Salicyclates cause worse nausea compared to others. Can be minimized by taking
with food, switching to enteric coated or buffered products

Can cause photosensitivity – avoid the sun during mid day hours, use sun protective clothing and broad
spectrum sunscreen

Dyspepsia, abdominal pain

Non-selective –

Ibuprofen (motrin, advil) – 200-400 mg q4-6h, max = 3.2 gm/day

Indomethacin (Indocin) high risk for CNS side effects (avoid in psych conditions). IR approved for gout

Naproxen (Aleve) – 200 mg q 8-12h or 500 mg q12h rx. Max = 1 gm/day

+esomeprazole = vimovo

Ketorolac (Toradol) – 10 mg q4-6h max 40 mg/day. IV: (>50 kg) 30 mg q6h

BBW: oral ketorolac for hosrt term moderate to sever acute pain only as continuation of iv or im
ketorolac max combined duration is 5 days. Not for intrathecal or epidural use. Avoid in pts with
advanced renal disease or at risk for renal impairment due to volume depletion.

Warnings – acute renal failure or liver failure or anaphylactic shock

Never used before surgery

Increased cox 2 selectivity –

Celecoxib (Celebrex) – 100 mg BID or 200 mg daily. RA 200 mg BID. Highest selectivity. Contraindicated
in sulfonamide allergy

Diclofenac (voltaren) – oral, gel. Avoid in women of child bearing potential.

Meloxicam (Mobic) – 7.5-15 mg daily

Nabumetone

Salicylate NSAIDs –

Aspirin (acetylsalicylic acid) – cardioprotective dosing = 81-162 mg once daily

Analgesic dose = 325-650 q4-6h

Avoid aspirin in children and teenagers with any viral infection dur to potential risk of Reyes syndrome

Salicylate overdose can cause tinnitus

NSAID drug interactions – additive bleeding risk with other agents that increase bleeding risk such as
steroids

Cautin using asa with other ototoxic agents (aminoglycosides, IV loops)

Do not take multiple nsaids together except when with low dose asa (1 hr before or 8 hrs after
ibuprofen)

Can increase the levels of lithium and methotrexate

Anti epileptics =

Gabapentin (Neurontin) max 3.6 gm/day

Pregabalin (lyrica) max 450 mg/day

SE: dizziness, somnolence, peripheral edema/weight gain

Lyrica approved for fibromyalgia, PHN and neuropathic pain associated with diabetes and spinal cord
injury

Carbamazepine (tegretol) – max 1.2 gm/day. Only FDA approved medication for tx of trigeminal
neuralgia

Anti depressants –

Amitriptyline (Elavil) – 10-50 mg qhs

Duloxetine (Cymbalta) – 30-60 mg/day

Musculoskeletal agents –

Side effects – excessive sedation, dizziness, confusion, asthenia (muscle weakness)

Antispasmodics with analgesic efects

Baclofen (lioresal) – 5-20 TID-QID prn

BBW: abrupt withdrawal of intrathecal baclofen has resulted in severe effects (high fever, lethargy,
rebound spasticity, muscle rigidity) leading to organ failure and death

Cyclobenzaprine (flexeril) – dry mouth. 5-10 mg TID prn. Serotonergic

Tizanidine (zanaflex) – 2-4 mg q6-8h max 36 mg/day. Cyp1a2. Hypotension and dry mouth.

Antispasmodics that exert effect through sedation

Carisprodol (Soma) – 250-350 QID

Metaxolone

Methocarbomol (Robaxin) – 1.5-2 gm QID prn

Topical adjuvants –

Lidocaine patches/gel

Capsaicin

Methylsalicylate (salonpas, icyhot)

Opioids –

Three opioid receptors (mu, kappa, delta). Mu receptor agonists in the CNS which primarily produces
pain relief but also causes euphoria and respiratory depression.

Boxed warnings –

Addiction

Respiratory depression

Use with other CNS depressants like benzos or alchol can increase risk of death

Accidental ingestion/exposure of even one dose in children can be fatal

Crushing ,dissolving or chewing long acting products can cause delivery of potentially fatal dose

Life threatening neonatal opioid withdrawal with prolonged use during pregnancy

REMS for all opioids

Can lead to:

Physical dependence (physical withdrawal symptoms: anxiety, tachycardia, shakiness, SOB)

Addiction: strong desire or compulsion to take drug despite harm, drug seeking behavior

Tolerance: higher dose is needed to produce the same level of analgesia

Hyperalgesia: pain become worse

Respiratory depression

Side effects – constipation, nausea/vomiting, somnolence, dizziness/lightheadedness and risk of

respiratory depression

Codeine – BBW respiratory depression and death have occurred in children following tonsillectomy or
adenoidectomy. CI children < 12 and <18 following the two aforementioned surgeries. 2d6 interactions

Fentanyl (duragesic) – patches. Apply I patch q72h. lozenge. 3a4 interactions. Hyperhidrosis, application
site erythema. Not used in opioid naïve patients. 60 mg morphine for at least 7 days. Patch – effect seen
8-16 hours after application. Hairless skin. Can be covered by bioclusive or tegaderm. Do not cover with
heating pad. Keep way from children and pets.

Hydrocodone IR (combo products only) – 5, 7.5, 10. Cyp3a4 interactions.

ER formulations

Hydromorphone (dilaudid) – opioid naïve 2-4 mg q4-6h. iv 0.2-1mg q2-3h. use in opioid tolerant patients
only

High risk for overdose. Potent

Methadone – 2.5-10 mg q8-12h. BBW life threatnening qtc prolongation and serious arrhythmias.
Variable half life = hard to dose safely. Can decrease testosterone and contribute to sexual dysfunction.
Used for detox and maintenance tx in addicted patients

Morphine (ER: ms contin, Injection duramorph, infumorph) – IR 10-30 mg q4h, ER: 15,30,60,100,200
mgq8-12h. more pruritus. Can use diphenhydramine. Start 2.5-5 IV q3-4h in naïve patients

Oxycodone – (IR Roxicodone, Cr oxycontin, combo Percocet) IR 5-20 mg q4-6h cr 10-80 mg q12h. cyp
3a4 interactions

Oxymorphone (opana) – IR 5-10 mg q4-6h prn. Take on empty stomach.

Drug interactions – CNS depressants: benzos, muscle relaxants. Avoid alcohol. Increased risk of
hypoxemia with underlying respiratory disease (COPD, sleep apnea).

Methadone – caution with agents that worsen cardiac function or increase arrhythmia risk. Cautin with
serotonergic agents.

Hydrocodone, fentanyl, methadone, and oxycodone are 3a4 substrates

tramadol = mu opioid receptor agonist and inhibitor of norepinephrine reuptake. Also inhibits reuptake
of serotonin.

(ultram) 50-100 mg q4-6h. max 400 mg /day

Warnings seizure risk, serotonin syndrome,

CI children <12 or <18 with tonsillectomy adeinoectomy

SE: dizziness, constipation, nausea, somnolence

Naloxone – opioid reversal through mu receptor antagonist

Narcan = nasal spray 4 mg

Evzio = auto injector

Iv solution

IV/IM/SC – 0.4-2 mg q2-3 min

s/sx of OD = extreme sleepiness, slow or shallow breathing, fingernails or lips turning blue, extremely
small pinpoint pupils, slow hearbeat, low bp

SE: withdrawal symptoms