A patient presents with dilated pupils, diaphoresis, piloerection, abdominal cramps, diarrhoea, and myalgia 12 hours after stopping heroin. The physiological mechanism of these symptoms is:

• A Serotonin excess due to loss of opioid-mediated inhibition
• B GABA-A receptor downregulation leading to seizure threshold reduction
• C Direct histamine release from mast cells
• D Noradrenergic hyperactivity from locus coeruleus disinhibition ✓

Explanation

Opioid receptors on the locus coeruleus (LC) normally inhibit noradrenergic neuronal firing. Chronic opioid use causes adaptive upregulation of LC neurons (neuroadaptation). On opioid withdrawal, the inhibitory restraint is removed, leading to LC hyperactivity and a surge of norepinephrine release. This explains the sympathetic storm of opioid withdrawal: mydriasis, diaphoresis, piloerection, tachycardia, diarrhoea, cramps, and intense autonomic distress. This is also why clonidine (alpha-2 agonist that suppresses LC firing) reduces withdrawal symptoms.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.