What causes nocturnal arm and leg pain in an adult when lying on them?

Nocturnal Arm and Leg Pain When Lying Down

The most likely cause of arms and legs aching all night when lying on them is Restless Legs Syndrome (RLS), which presents as uncomfortable sensations and an urge to move the limbs that worsens with rest and at night, though you must also consider nocturnal leg cramps, peripheral neuropathy, and positional nerve compression.

Key Diagnostic Features to Distinguish the Cause

Restless Legs Syndrome (Primary Consideration)

RLS is characterized by an overwhelming urge to move the limbs accompanied by unpleasant sensations (aching, tingling, creepy-crawly feelings) that worsen during rest and at night. 1, 2 The critical distinguishing features include:

• Symptoms worsen specifically in the evening or at night and improve toward morning 1
• Rest or inactivity triggers or worsens symptoms (sitting or lying down) 1, 2
• Movement provides relief - walking, stretching, or rubbing helps as long as the activity continues, but symptoms return when you stop moving 1, 2
• Both upper and lower extremities can be affected, not just legs 1
• The sensations are described as aching, burning, itching, or tingling rather than sharp pain 1

Nocturnal Leg Cramps (Alternative Diagnosis)

If the pain is different in character, consider nocturnal leg cramps, which present as:

• Painful, involuntary muscle contractions typically in the calf with a tightening sensation 3, 4
• No urge to move the legs - this is the key difference from RLS 3
• Relief comes specifically from stretching the affected muscle, not general movement 3
• Pain is sharp and cramping rather than dysesthesias 3

Positional Nerve Compression

If symptoms are affected by specific body positions during sleep, consider spinal stenosis or nerve compression, particularly if there is accompanying peripheral neuropathy 5. This can mimic RLS but has positional triggers.

Essential Clinical Questions to Ask

To differentiate these conditions, ask these specific questions 3, 6:

1. "What does it feel like?" - Cramps cause painful tightening; RLS causes an urge to move with dysesthesias
2. "Is it relieved by movement?" - RLS improves with any movement but returns when stopping; cramps improve only with stretching the specific muscle
3. "When does it occur?" - RLS worsens in evening/night and with rest; cramps are more random
4. "Does it come back a few minutes after you sit or lie back down?" - This suggests RLS rather than cramps

Recommended Evaluation

Physical Examination

• Perform a thorough neurological exam looking for signs of peripheral neuropathy or radiculopathy 1, 3
• Assess vascular status including pulses and signs of arterial insufficiency 3, 6
• Look for signs of venous varicosities 1, 3

Laboratory Testing

Check serum ferritin levels - values less than 50 ng/mL are consistent with RLS and indicate need for iron supplementation 1, 7, 2. Transferrin saturation less than 20% also warrants iron replacement 2.

Additional labs to consider if secondary causes are suspected 6:

• Electrolytes and renal function
• Thyroid function
• Calcium levels
• HbA1c (if diabetic neuropathy suspected)

Medication Review

Review all medications, as several can exacerbate RLS 1:

• Tricyclic antidepressants
• SSRIs
• Lithium
• Dopamine antagonists (antipsychotics)
• Centrally acting H1 antihistamines (diphenhydramine) 2

Medications associated with cramps include diuretics, calcium channel blockers, and NSAIDs 6.

Treatment Approach

For Restless Legs Syndrome

First-line treatment is gabapentinoids (gabapentin, gabapentin enacarbil, or pregabalin), as approximately 70% of patients have much or very much improved symptoms versus 40% with placebo 7, 2.

Iron supplementation is essential if ferritin ≤100 ng/mL or transferrin saturation <20% 2:

• Ferrous sulfate 325-650 mg daily or every other day (oral)
• Intravenous iron 1000 mg for more severe deficiency

Dopamine agonists (ropinirole, pramipexole) are no longer first-line due to augmentation risk (7-10% annual incidence), though they may be considered for short-term use in select patients 1, 7, 2.

For Nocturnal Leg Cramps

• Stretching exercises before bed 4
• Adequate hydration 6
• Avoid prolonged positioning of joints at end range 6
• Limited evidence supports magnesium, calcium channel blockers, or vitamin B12 4

Critical Pitfalls to Avoid

• Do not assume electrolyte depletion causes nocturnal leg cramps without evidence - this theory is poorly supported 3
• Do not order polysomnography for simple diagnosis of RLS or cramps - diagnosis is clinical 1, 3
• Do not confuse cramps with RLS, as this leads to inappropriate dopaminergic therapy when stretching would suffice 3
• Do not overlook positional factors - if symptoms change with body position, consider spinal stenosis, especially in diabetic patients 5
• Do not miss iron deficiency - check ferritin even if hemoglobin is normal, as low-normal iron stores contribute to RLS 1, 2

Associated Conditions to Consider

RLS is common in patients with 2:

• Multiple sclerosis (27.5%)
• End-stage kidney disease (24%)
• Iron deficiency anemia (23.9%)
• Pregnancy, especially third trimester (22%)
• Peripheral neuropathy (21.5%)
• Parkinson disease (20%)

Up to 90% of RLS patients have associated periodic limb movements during sleep, which may cause brief awakenings the patient is unaware of 3, 7.