SN6
SHORT NOTE
5M
Write a short note on denervation hypersensitivity.
Definition
Denervation hypersensitivity = the increased sensitivity of a structure to its chemical transmitter, or to related substances, after its nerve supply has been interrupted.Also called the law of denervation (Cannon).
Mechanism
Nerve section → No transmitter released → Two adaptive changes → 1. Receptors spread over the whole membrane (up-regulation) → 2. Loss of reuptake and of degrading enzymes → Marked supersensitivity to circulating transmitter
- Normally receptors are confined to the junctional region; after denervation they appear over the entire cell surface
- The greater the distance of the lesion from the effector, the greater the sensitivity — postganglionic section produces more supersensitivity than preganglionic
Examples
| Structure denervated | Result |
|---|---|
| Skeletal muscle | Acetylcholine receptors spread along the whole fibre → fibrillation; exaggerated response to ACh |
| Iris (Horner syndrome) | Supersensitive to adrenaline; the basis of pharmacological localisation tests |
| Denervated heart (transplant) | Exaggerated response to circulating catecholamines; no vagal slowing, so resting rate is high and there is no response to carotid massage or atropine |
| Smooth muscle after sympathectomy | Exaggerated vasoconstriction to circulating noradrenaline — why the benefit of sympathectomy may wane |
| Adrenalectomised animal | Supersensitive to catecholamines |
Clinical Importance
- Succinylcholine is dangerous in denervated or burnt muscle — the spread of receptors causes massive K+ release and fatal hyperkalaemia. This is a genuine anaesthetic hazard
- Fibrillation potentials on EMG confirm denervation 2–3 weeks after nerve injury
- Pharmacological tests in Horner syndrome exploit it to localise the lesion
- Cardiac transplant recipients need direct-acting agents such as isoprenaline; indirect agents like ephedrine and atropine do not work
Related Phenomena
- Receptor up-regulation also follows prolonged pharmacological blockade — hence the rebound tachycardia and angina on abruptly stopping a β blocker
- Down-regulation is the converse — chronic agonist exposure reduces receptor number, producing tolerance, as with β2 agonists in asthma
- Withdrawal syndromes of opioids, alcohol and benzodiazepines all involve up-regulated receptors suddenly deprived of the drug
- Clonidine withdrawal → rebound hypertensive crisis, from up-regulated α1 receptors
- Wallerian degeneration must occur first — supersensitivity takes days to weeks to develop, in parallel with receptor spread
- Cannon and Rosenblueth first described the law of denervation in 1949
All questions in Autonomic Nervous System & Integrative Physiology
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