What is the likely cause of nighttime painful urination in a 25-year-old female with a history of interstitial cystitis, depression, mild scoliosis, and intermittent low back pain, who has not taken Macrobid (Nitrofurantoin) recently and has a normal urine test?

Differential Diagnosis for Nighttime-Only Painful Urination

This presentation most likely represents an IC/BPS flare with nocturnal predominance, though you must also consider pelvic floor dysfunction, neuropathic pain from her scoliosis, and psychosomatic amplification related to her depression. 1

Primary Consideration: IC/BPS Flare with Atypical Presentation

The most probable diagnosis is an interstitial cystitis flare presenting with nocturnal symptoms only, which can occur even with normal urinalysis. 2, 3

• IC/BPS pain typically worsens with bladder filling and improves with urination, and many patients describe symptoms as "pressure" rather than pain. 1
• Symptom flares can suddenly intensify for hours, days, or weeks with variable presentations—not all patients have classic daytime frequency. 1
• The normal urinalysis does not exclude IC/BPS, as this condition is defined by symptoms lasting more than six weeks in the absence of infection or other identifiable causes. 2
• Nighttime predominance may reflect increased bladder filling during sleep or positional changes affecting pelvic structures. 3

Secondary Considerations

Pelvic Floor Dysfunction

• There is a high rate of levator ani pain in women with IC/BPS, suggesting pelvic floor muscle involvement contributes to symptoms. 1
• Her scoliosis and intermittent low back pain indicate musculoskeletal dysfunction that could cause pelvic floor hypertonicity. 1
• Pelvic floor spasm can cause positional pain that worsens when supine (nighttime), creating urethral/bladder neck irritation perceived as dysuria. 1

Neuropathic Pain from Spinal Pathology

• Her mild scoliosis with intermittent low back pain raises the possibility of nerve root irritation affecting sacral dermatomes (S2-S4) that innervate the bladder. 1
• Neuropathic pain can have circadian variation and worsen at night when distractions are minimal. 1
• IC/BPS may be part of a generalized systemic disorder affecting multiple somatic/visceral organs with overlapping symptoms and pathophysiology. 1

Depression-Related Pain Amplification

• IC/BPS patients frequently exhibit mental health disorders including depression, with evidence suggesting a common biological mechanism rather than purely reactive symptoms. 1
• Depression is associated with sleep dysfunction, catastrophizing, and heightened pain perception that could amplify nocturnal bladder sensations. 1
• Central sensitization in depression can lower pain thresholds, making normal bladder filling painful. 1

Hunner Lesions (Less Likely but Must Exclude)

• Cystoscopy should be performed if Hunner lesions are suspected, as this is the only reliable way to diagnose their presence. 2
• Hunner lesions represent a specific IC/BPS subtype requiring fulguration and/or triamcinolone injection. 4
• However, the normal urinalysis and lack of daytime symptoms make this less likely. 2

Critical Diagnostic Steps

Do not treat with antibiotics when no infection is present—this leads to antibiotic resistance and disruption of protective flora. 2

Immediate Assessment Required:

• Detailed pain characterization: location (suprapubic, urethral, pelvic), quality (burning, pressure, aching), and relationship to bladder filling/voiding. 1
• Document baseline symptoms using validated tools (GUPI, ICSI, or VAS) to measure treatment effects. 4
• Assess for other IC/BPS comorbidities: fibromyalgia, irritable bowel syndrome, chronic fatigue, vulvodynia. 1
• Pelvic floor examination to identify levator ani tenderness or hypertonicity. 1
• Evaluate depression control and current medications, as inadequate treatment may worsen pain perception. 1

Consider Cystoscopy If:

• Symptoms persist despite empiric IC/BPS treatment. 2
• Hunner lesions are suspected based on severe symptoms or hematuria. 2, 4
• Diagnostic uncertainty remains after initial evaluation. 2

Common Pitfalls to Avoid

• Do not dismiss symptoms because urinalysis is normal—IC/BPS is diagnosed by symptoms in the absence of infection, not by laboratory findings. 2
• Do not delay treatment waiting for "classic" IC/BPS presentation—symptom patterns vary widely, and early intervention improves outcomes. 1, 2
• Do not overlook the musculoskeletal component—her scoliosis and back pain may directly contribute through pelvic floor dysfunction or nerve irritation. 1
• Do not attribute symptoms solely to psychiatric causes—while depression coexists with IC/BPS, there is evidence of shared biological mechanisms rather than purely psychosomatic etiology. 1