Ankle Sprain

Anatomy and mechanism

• Anterior talofibular ligament (ATFL) - weakest, intracapsular, injured first (isolated ATFL injury accounts for about two-thirds of sprains) - Rosen's Emergency Medicine, p. 740; Miller's Review of Orthopaedics.
• Calcaneofibular ligament (CFL) - injured next if force continues (~20% of sprains involve both ATFL + CFL).
• Posterior talofibular ligament (PTFL) - strongest, rarely involved - Bailey and Love's Short Practice of Surgery, p. 526.

Grading (functional/pathologic classification)

Clinical exam

• Anterior drawer test: ankle in slight plantarflexion, anterior force on calcaneus with posterior counterforce on tibia - excess anterior translation vs. the uninjured side suggests ATFL injury.
• Talar tilt test: varus stress with the ankle in slight plantarflexion (ATFL) or slight dorsiflexion (CFL) - excessive tilt indicates the corresponding ligament is torn - Bailey and Love's Short Practice of Surgery, p. 526.
• Point tenderness over the ATFL/CFL without fibular bone tenderness supports sprain over fracture - Pfenninger and Fowler's Procedures for Primary Care.

Imaging - Ottawa Ankle Rules

• Bone tenderness along the distal 6 cm of the posterior tibia or tip of the medial malleolus
• Bone tenderness along the distal 6 cm of the posterior fibula or tip of the lateral malleolus
• Inability to bear weight for four steps, both immediately after injury and in the clinic/ED

Management

• Grade I-II: functional bracing (e.g., Aircast) rather than rigid casting is generally preferred - a below-knee cast/Aircast speeds early recovery versus a simple compression bandage, though outcomes converge by 9 months - Goldman-Cecil Medicine, p. 3846.
• Grade III: may need longer immobilization; surgery is considered for persistent instability or high-demand athletes, not routinely in the acute setting.

Recent evidence (last 1-3 years)

• A 2025 meta-analysis found functional treatment generally outperforms immobilization for acute ankle sprains in return to activity (PMID: 40954619).
• A 2025 meta-analysis/trial sequential analysis supports physical therapy over conventional treatment alone for grade I-II acute sprains in reducing pain and improving function (PMID: 41023742).
• A 2023 systematic review noted that many current rehab protocols for lateral ankle sprain don't fully target the actual biomechanical mechanisms of re-injury (e.g., insufficient emphasis on reactive neuromuscular control), suggesting room to improve standard proprioceptive programs (PMID: 36716507).

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

Mechanism of action

• COX-1: constitutive, protects gastric mucosa, supports platelet aggregation and renal blood flow.
• COX-2: inducible at sites of inflammation; selective COX-2 inhibitors (e.g., celecoxib) were designed to reduce GI toxicity while retaining anti-inflammatory effect, at the cost of increased cardiovascular risk.

Common agents

Use in ankle sprain / soft tissue injury

Adverse effects and who's at risk

• GI: dyspepsia, ulcers, bleeding - risk increased with age, tobacco/alcohol use, concurrent corticosteroids, or history of peptic ulcer disease.
• Renal: reduced renal blood flow via prostaglandin inhibition - risk increased with dehydration, hypovolemia, pre-existing renal impairment, or concurrent ACE inhibitors/ARBs/diuretics.
• Cardiovascular/hepatic: can worsen heart failure or liver disease, especially when combined with ACE inhibitors, ARBs, or diuretics.
• Bronchospasm in patients with asthma and aspirin hypersensitivity.
• Pregnancy: avoid in the third trimester - can prolong gestation or cause premature closure of the ductus arteriosus.
• Drug interactions: increases lithium levels (reduces excretion) - watch for lithium toxicity (confusion, tremor, dysrhythmia); reduces natriuretic effect of diuretics.

Practical rule

Recent evidence note

Which NSAID is most effective for ankle sprain?

What the evidence shows

• Celecoxib vs. maximum-dose ibuprofen (Petrella et al., PMID 12216965): celecoxib was as effective as ibuprofen for ankle sprain pain, with better GI tolerability - useful if a patient has GI risk factors.
• Celecoxib vs. diclofenac slow-release (Nadarajah et al. 2006): comparable efficacy in an Asian population cohort.
• Diclofenac vs. placebo: significant reduction in pain at rest and on weight-bearing within 72 hours - one of the better-studied individual agents for this indication.
• Ibuprofen vs. extended-release acetaminophen (noninferiority RCT, AFP summary): acetaminophen ER 3900 mg/day was comparable to ibuprofen 1200 mg/day for grade I-II lateral ankle sprains - reinforcing that NSAID superiority over non-NSAID analgesics isn't well established either.
• Valdecoxib showed efficacy in trials but was withdrawn from the market (cardiovascular safety concerns) and isn't a practical option now.

Practical recommendation

• Ibuprofen - first-line for most people: cheap, OTC, well-studied, favorable safety in patients without GI/renal risk factors.
• Naproxen - reasonable alternative, longer half-life allows less frequent dosing.
• Topical diclofenac gel - good option if you want to minimize systemic GI/renal exposure, or in patients with relative contraindications to oral NSAIDs.
• Celecoxib (COX-2 selective) - consider if the patient has GI risk factors (history of ulcer, elderly, concurrent steroid use) and no cardiovascular contraindications, since it showed comparable efficacy to ibuprofen with better GI tolerability in trials.

• Acute Ankle Sprain Management: An Umbrella Review of Systematic Reviews
• Ankle sprain: the effects of non-steroidal anti-inflammatory drugs (PMC)

Injection therapy for ankle sprain

Corticosteroid injection

• Used mainly for persistent/chronic pain after a sprain, particularly when the cause is lateral gutter synovitis or soft-tissue impingement rather than ongoing mechanical instability.
• Best considered if symptoms persist beyond ~3 months, are disrupting sleep, or are limiting the patient's ability to engage in physiotherapy - it can provide a "window of opportunity" of pain relief to allow rehab to proceed effectively. Combining a corticosteroid injection with a structured physiotherapy program (starting within about 2 weeks) gives better outcomes than the injection alone.
• Typically delivered under ultrasound guidance for accuracy and lower complication risk versus landmark-guided injection.
• Not indicated for the acute setting as routine treatment - about 10% of lateral ankle sprains fail conservative management and might be candidates for this if instability/impingement is the driver of ongoing pain.
• Caution: corticosteroid injections are one of the recognized factors that can impair ligament healing, so they're avoided in the acute/subacute phase and generally not injected directly into a healing ligament - Miller's Review of Orthopaedics.

Platelet-rich plasma (PRP)

• A 2020 RCT (Blanco-Rivera et al., PMID 31640921) found PRP injection into the anterior talofibular ligament reduced pain and improved function in patients with lateral ankle sprain compared to controls, with benefit most evident at 5-8 weeks; outcomes converged with controls by around 6 months.
• A follow-up study using two PRP injections (versus one, or none) found the two-injection group had better short-term pain/function and better ATFL tissue quality on imaging (MRI signal-to-noise ratio) at final follow-up, though all groups looked similar by 6-12 months.
• Overall, current evidence is described as "moderate" - PRP appears to speed early symptom relief and functional recovery, but doesn't clearly change the long-term outcome compared to standard care.
• PRP is also being studied for chronic lateral ankle instability (case series show improvement in instability symptoms and functional scores), and for ankle syndesmosis injuries specifically (a small study in rugby players).

Practical takeaway

• Acute sprain: no routine role for injections - stick with PRICE, early functional mobilization, bracing, and progressive rehab as discussed earlier.
• Persistent pain/synovitis after failed conservative care: ultrasound-guided corticosteroid injection combined with physiotherapy is reasonable.
• Interest in accelerating healing/reducing recurrence risk, especially in athletes: PRP has supportive but still evolving evidence, mainly benefiting the first 5-8 weeks rather than changing long-term prognosis. It's not yet a standard-of-care recommendation, more something considered on a case-by-case basis, often in sports medicine settings.
• Neither corticosteroid nor PRP injection is a substitute for the mechanical rehab (proprioception, peroneal strengthening) that drives functional recovery and reduces re-injury risk.