Pain, Analgesia, and Anesthesia

Pain

Protective signal → indicates tissue injury or threat

Generated by nociceptors → CNS processing → perception

Influenced by biological, psychosocial, social

Nociception ≠ pain (physiologic signal ≠ experience/perception)

Pain Pathway

1. Transduction

2. Transmission

3. Perception

4. Modulation

Target of all analgesics

1. Transduction

Tissue injury → inflammatory mediators → nociceptor activation

NSAIDs, corticosteroids

2. Transmission

Signal travels → peripheral nerve → spinal cord → brain

Local anesthetics

3. Perception

Brain interprets signal → “pain experience”

Opioids

4. Modulation

CNS increases or decreases pain signal (endorphins, descending pathways) → reduction in perception

Antidepressants, anticonvulsants

Pain Transduction

Stimulus → sodium ion channels open → action potential → signal to CNS

Inflammation lowers pain threshold (increases sensitivity)

Pain Facilitator Mediators

Increase pain

• Prostaglandins: Sensitize nociceptors

• Bradykinin: Direct nociceptor activation

• Substance P: Amplifies signal in spinal cord

• Histamine: Inflammation + swelling

Pain Inhibitors

Decrease pain

• Endorphins: Natural opioids

• Endocannabinoids: Modulate pain

Acute Pain

Usually sudden onset, result from an injury

Protective (signals injury)

Sympathetic activation: Increases HR/BP/RR, diaphoresis

Resolves with healing

Chronic Pain

Long-term, not a symptom (disease or disorder)

CNS remodeling + persistent signaling

Minimal physiologic response

Psychological + functional impact

Nociceptive Pain

Acute pain

Tissue injury

Somatic: Sharp, localized

Visceral: Deep, diffuse

Neuropathic Pain

Acute pain

Nerve damage

Burning, tingling, electric

Inflammatory Pain

Acute pain

Swelling, aching, throbbing

-itis

Bradykinin + prostaglandins

Central Pain

Acute pain

Processing disorder

No clear injury (fibromyalgia)

Chronic pain syndrome — person is too sensitive to pain (excessive pain response)

NSAIDs

Inhibit COX → decrease prostaglandins

Decrease pain/inflammation/fever

ADR: GI bleeding (decrease of protective prostaglandins), renal injury → decreased renal perfusion (hypovolemia), increased BP

Acetaminophen

Acts in CNS → decreases prostaglandins (minimal peripheral effect)

Decreases pain/fever; NO anti-inflammatory effect

ADR: Hepatotoxicity

Max: 4g/day (healthy), ≤3g/day (hi risk)

NOT an NSAID

Opioid Agonists

Central pain modulation

Bind µ receptors → decrease pain perception + emotional response

Analgesia, sedation, euphoria

ADR: RESPIRATORY DEPRESSION, constipation, dependence

Naloxone/Narcan

Pain signal present → perception + emotional response reduced

Mu Opioid Receptor

Analgesia, respiratory depression, euphoria

Kappa Opioid Receptor

Spinal analgesia, sedation

Delta Opioid Receptor

Minor role

Opioid + Non-Opioid

Additive effect. Better pain control. Risk of dose ceiling (toxicity from non-opioid)

Ex: Vicodin, Norco, Percocet, Tylenol #3

Acetaminophen overdose → liver failure

Pain Assessment

OPQRST. Effect on functions (ADLs, mobility). Influencing factors? (Biological, Psychological, Social)

Ineffective Pain Management Effects

1. CV — increased HR, BP, cardiac workload

2. Pulmonary — hypoventilation, atelectasis, infection

3. GI — post-op ileus, constipation, urinary retention

4. Muscular — weakness, fatigue

5. Psychological — anxiety, fear, frustration

Pain Management Principles

Reduce pain and improve function

Multimodal: Non-pharm + pharmacologic

Individualize dosing + manage ADRs

Reassess pain + function

Adjuvant Meds

Not primary analgesics — enhance pain control

• Antidepressants (TCAs, SSRIs) → neuropathic pain

• Anticonvulsants (gabapentin, pregabalin) → neuropathic pain

• Corticosteroids → inflammatory pain

Morphine

Prototype. Opioid agonist. Narcotic analgesic.

Binds to mu/kappa opioid receptors in the CNS to alter pain perception

Severe acute pain, chronic pain, preanesthetic sedation

ADR: Respiratory depression, sedation, nausea, vomiting, constipation, urinary retention

SCHEDULE II, extended release for opioid-tolerant clients only, not for prn use

Monitor bowel function, sedation, respiratory depression

Oral, IV, subcutaneous

Fentanyl

Opioid agonist. IV anesthetic

Binds to mu/kappa opioid receptors for potent, rapid analgesia

Short-duration analgesia, chronic pain management, severe pain in controlled settings

ADR: Respiratory depression, bradycardia, hypotension, muscle rigidity

SCHEDULE II. Hi abuse/misuse risk, overdose, and CNS depressant interaction

50-100x more potent than morphine

Airway support, monitor for respiratory depression. Titrate carefully (esp opioid-naive)

IV, transdermal patches, lozenges

Tramadol

Synthetic opioid analgesic

Binds to mu receptor. Weak opioid agonist. Inhibits norepinephrine/serotonin reuptake, inhibits pain transmission impulse

Moderate pain, neuropathic pain (off-label), restless leg syndrome

ADR: Dizziness, N/V, lethargy, CNS stimulation, seizures (lowers threshold)

Contraindications: Seizure history, combination use with SSRIs/MAOIs. Sudden death w/ ethanol

Monitor for seizures, avoid alcohol/CNS depressants, assess risk for serotonin syndrome. Schedule IV

Anesthesia

Medically induced, reversible state of loss of sensation, w or w/o consciousness. Used to prevent pain during procedures.

Sedation → moderate sedation → deep sedation → general anesthesia

General Anesthesia

Loss of sensation + loss of consciousness

Increases GABA (inhibitory) and decreases NMDA (excitatory). Lowers BP

Risk: Respiratory depression, hypotension

G for gas

Regional Anesthesia

Loss of sensation in a body region, consciousness intact

Used for procedures below level (ex: spinal, epidural)

Local Anesthesia

Loss of sensation in a small area, consciousness intact

Used for minor procedures

Sedation Anesthesia

Reduced awareness ± mild decreased sensation

Consciousness variably depressed

Used for procedures requiring relaxation/anxiolysis

Isoflurane

Inhaled general anesthetic. ↑GABA + ↓NMDA

↑GABA + ↓NMDA signaling → global CNS depression → anesthesia

Indications: Induction + maintenance of general anesthesia

ADR: Hypotension, respiratory depression, N/V. Malignant hyperthermia (genetic mutation), arrhythmias, hepatotoxicity

Contraindications: Malignant hyperthermia, severe hepatic disease

Nitrous Oxide

Inhaled anesthetic. CNS depressant. Laughing gas

NMDA receptor antagonist → blocks excitatory glutamate signaling → mild anesthesia + analgesia

Rapid onset + rapid recovery. Weak anesthetic (used with other agents)

ADR: Nausea, dizziness, sedation. Diffusion hypoxia (IF not given w/ O2)

Contraindications: Air-filled space conditions (pneumothorax, bowel obstruction)

MUST BE ADMINISTERED W/ O2

Propofol

General anesthetic. GABA agonist.

Enhances GABA activity → increases inhibitory signaling → rapid CNS depression → sedation/anesthesia

Rapid onset + short duration, no analgesic effect

ADR: Respiratory depression, HYPOTENSION, bradycardia; propofol infusion syndrome (PRIS, prolonged use)

Contraindications: Hemodynamic instability, caution if egg/soy allergy

Combine with analgesics

Sedatives

Stimulate GABA. CNS depressants that induce relaxation and amnesia

Used for conscious sedation during minor procedures

ADR: Respiratory depression, hypotension, drowsiness

Monitor RR and BP

Ex: Midazolam (Versed), Diazepam (Valium)

Midazolam

Sedative/Anxiolytic. Benzodiazepine (GABA agonist)

Enhances GABA → increases inhibitory signaling → sedation, anxiolysis, amnesia

Rapid onset, anterograde amnesia, no analgesic effect

ADR: Respiratory depression, hypotension, drowsiness. Respiratory arrest (serious, w/ other CNS depressants)

Contraindications: Severe respiratory depression, caution w/ concurrent CNS depressants

Combine w/ analgesics if needed. Monitor respiratory status, BP, level of sedation. Ensure airway support.

REVERSAL AGENT IS FLUMAZENIL

Neuromuscular Blockers/Relaxers

Paralysis only (no sedation, analgesia, amnesia)

Block ACh at nicotinic receptors (NMJ) → decrease muscle contraction → paralysis

Indications: Intubation (diaphragm is paralyzed), surgical/mechanical ventilation paralysis

ADR: Respiratory paralysis, malignant hyperthermia, bradycardia, hypotension

Ex: Succinylcholine, Rocuronium

Always give w/ analgesia + sedation first, airway/reversal agents should be ready

Succinylcholine

DEPOLARIZING neuromuscular blocker. Nicotinic receptor agonist,

Persistent activation of nicotinic receptor → sustained depolarization → paralysis. Initial depolarization → fasciculations → flaccid paralysis

Muscle contraction till exhaustion, breaks down muscle cells containing potassium → hyperkalemia

Indications: Rapid sequence intubation, short procedures

ADR: HYPERKALEMIA, bradycardia, malignant hyperthermia, respiratory arrest

Contraindications: Hyperkalemia risk, history of malignant hyperthermia

Must be given with sedation

Rocuronium

NONDEPOLARIZING neuromuscular blocker. Nicotinic receptor antagonist

Competitively blocks acetylcholine at nicotinic receptors (NMJ) → prevents depolarization → skeletal muscle paralysis

NO depolarization → NO fasciculations → flaccid paralysis

Indications: Rapid sequence intubation, surgical muscle relaxation, mechanical ventilation support

Must be given with sedation/anesthesia

Reversal: Sugammadex, Neostigmine

Malignant Hyperthermia

Genetic (autosomal dominant) mutation. Mutation in RYR1 receptor → Ca2+ release → sustained metabolic contraction → triggers hypermetabolic crisis

Triggers: Volatile (inhaled) anesthetics + succinylcholine

Effects: Hyperthermia, acidosis, hyperkalemia, rhabydomyolysis

Treatment: DANTROLENE (antidote), stop trigger, supportive care

Get family history before anesthesia

Dantrolene

Malignant hyperthermia antidote. Skeletal muscle relaxant. Ryanodine receptor antagonist.

Blocks Ca2+ release from sarcoplasmic reticulum → decreased muscle contraction → decreased hypermetabolism

Indications: Malignant hyperthermia, neuroleptic malignant syndrome (NMS), severe muscle spasticity

ADR: Muscle weakness, drowsniess. HEPATOTOXICITY

Contraindications: Severe liver disease

Early administration is life-saving. Monitor LFTs, assess muscle strength, respiratory status.

Local Anesthetics

Block nerve signal transmission

Block sodium channels → prevent depolarization → stop action potentials → stop transmission

Pain never reaches CNS

Toxicity: CNS seizures, cardiac arrhythmias

Ex: Lidocaine, bupivacaine

Lidocaine/Xylocaine

Local anesthetic, antiarrhythmic. Amide-type sodium channel blocker.

Blocks voltage-gated Na+ channels → prevents depolarization → stops nerve conduction.

For numbing. Pain signal never reaches CNS.

Indications: Local/Regional anesthesia (injection, topical). Ventricular arrhythmias (IV)

ADR: Dizziness, confusion, seizures. Arrhythmias, hypotension

Contraindications: Severe heart block

Systemic toxicity → CNS + cardiac effects

Monitory ECG, BP, neurologic status. Watch for early toxicity (tinnitus, metallic taste, confusion)