Nerve physiology in four lines
- Resting membrane potential about −70 mV; threshold about −50 to −60 mV.
- Depolarization: voltage-gated sodium channels open and Na⁺ rushes in. Repolarization: K⁺ leaves the cell.
- Myelinated fibers conduct by saltatory conduction between nodes of Ranvier; blocking about 3 consecutive nodes (roughly 8–10 mm of nerve) is needed to stop the impulse reliably.
- Order of loss (commonly taught): pain → temperature → touch → pressure → motor function; recovery is roughly the reverse.
Mechanism (specific receptor theory)
- Local anesthetics are weak bases supplied as water-soluble hydrochloride salts. In tissue they exist as two forms: uncharged base (RN) and charged cation (RNH⁺).
- The uncharged base crosses the nerve sheath and membrane; inside the axon it re-equilibrates and the cation binds the receptor inside the sodium channel, blocking Na⁺ entry.
- Result: the membrane never reaches threshold, so no action potential is propagated. The resting potential itself is not changed.
- Nerve bundles: mantle fibers (outer) supply proximal areas and are blocked first; core fibers supply distal areas (e.g., incisors in an IANB) and are blocked last.
Properties that predict clinical behavior
| Property | Controls | Rule |
|---|---|---|
| pKa | Onset | Lower pKa → more uncharged base at tissue pH → faster onset |
| Lipid solubility | Potency | More lipid-soluble → more potent (bupivacaine is very lipid-soluble) |
| Protein binding | Duration | Higher binding to channel proteins → longer duration (bupivacaine about 95%) |
| Vasodilating activity | Duration and toxicity | More vasodilation → faster absorption, shorter action, higher blood levels |
- Henderson–Hasselbalch: at pH 7.4 a drug with pKa 7.9 has a base fraction of 1 ÷ (1 + 10^0.5) ≈ 24%; if tissue pH falls to 6.4 the base fraction drops to about 3%.
Why infected tissue is hard to numb
- Inflamed or infected tissue is acidic, so more drug stays as the charged cation, which cannot cross the nerve membrane.
- Inflammation also sensitizes nerves (lower threshold, more TTX-resistant sodium channels) and increases local blood flow that carries drug away.
- Practical fixes: block the nerve away from the inflamed site (e.g., IANB rather than infiltration over an abscess), supplemental techniques (intraosseous, PDL, intrapulpal), and preoperative NSAIDs.
⚠️ Common traps
- Saying the cation crosses the membrane: the uncharged base crosses; the cation does the blocking inside.
- Saying local anesthetics hyperpolarize the membrane or change resting potential.
- Linking pKa to potency: pKa predicts onset; lipid solubility predicts potency; protein binding predicts duration.
- Expecting the incisors to be numb first after an IANB: core fibers to distal teeth are blocked last.
Mini-quiz
- Which property mainly determines how quickly a local anesthetic takes effect?
- Which form of the local anesthetic binds the receptor in the sodium channel?
- Why is a local anesthetic less effective in an abscessed area?
- Which sensation is usually lost first after a nerve block?
- Bupivacaine's long duration is best explained by its high:
Answer key: 1 C · 2 B · 3 B · 4 C · 5 A