Chronic Aching in the Middle of the Instep Isn’t Just a Lingering Sprain — Not Confusing Lisfranc Joint Osteoarthritis (Tarsometatarsal Arthrosis) With Ankle-Sprain Sequelae or Flatfoot Pain: Dr. Moriwaki on Where Stem Cell Conditioned Media Joint Injection Can Address Intra-articular Inflammation and Where It Cannot Correct Bony Deformity2026.08.05

“The middle of my instep throbs the moment I start walking.” “Even lacing up my shoes hurts right there.” When such midfoot pain has lingered for months to years, some patients dismiss it as lingering ankle-sprain sequelae or simple fatigue, while an underlying chronic degenerative arthritis called Lisfranc joint osteoarthritis (tarsometatarsal arthrosis) is quietly progressing. Among the patients who come to our clinic for foot and ankle pain, there have been cases where self-diagnosis attributed the symptom to post-sprain sequelae, adult-acquired flatfoot, or Achilles tendinopathy — until a weight-bearing radiograph established the diagnosis of Lisfranc joint osteoarthritis. In this column, Dr. Moriwaki of AVAN TOKYO Ginza organizes the pathology of this chronic midfoot pain and where stem cell conditioned media joint injection can and cannot help.

Key Points of This Article

– Lisfranc joint osteoarthritis is a chronic degenerative disease in which cartilage wear, osteophyte formation, and joint-space narrowing progress at the midfoot (tarsometatarsal joints); it is easily mistaken for post-sprain sequelae, flatfoot pain, or Achilles tendinopathy.

– Bony deformity and joint-space narrowing themselves cannot be reversed by conservative treatment, but the chronic-synovitis-driven pain cycle inside the joint is a legitimate target of stem cell conditioned media joint injection.

– Acute Lisfranc fracture-dislocation (from sports or falls) is a different entity; the acute phase requires urgent orthopedic evaluation and surgical decision-making, not injection therapy.

– Diagnosis requires weight-bearing radiographs, careful clinical localization of tenderness, and MRI when indicated to assess cartilage status and bone marrow edema.

– Stem cell conditioned media should be positioned as one conservative option to modulate the intra-articular inflammatory environment and lower the pain baseline — not as a treatment that reverses deformity.

What Is Lisfranc Joint Osteoarthritis — A Degenerative Disease Advancing Quietly at the Midfoot

The Lisfranc joint complex is where the bases of the metatarsals meet the tarsal bones (the medial, intermediate, and lateral cuneiforms and the cuboid), forming five joints lined up horizontally across the instep. It functions as the rocker keystone during the push-off phase of gait; the second tarsometatarsal joint in particular has a deep bony recess and is a hotspot for concentrated weight-bearing stress. Repeated overload here drives cartilage wear, osteophyte formation, and joint-space narrowing over several to over a dozen years, producing chronic midfoot pain and focal swelling. This is Lisfranc joint osteoarthritis. Backgrounds include idiopathic disease, secondary arthrosis after previous Lisfranc injury, inflammatory arthritis from rheumatoid disease, and diabetic Charcot foot; clinically we see it relatively often in women in their 40s to 60s.

Differential Points So You Don’t Mistake It for Post-Sprain Sequelae or Flatfoot Pain

The pain of tarsometatarsal arthrosis is characterized by focal tenderness at the middle of the instep (base of the second to third metatarsals) and activity-dependent pain that worsens with push-off during gait. First-step pain in the morning and throbbing after prolonged standing are also typical. In contrast, post-sprain ankle sequelae center around the lateral malleolus; adult-acquired flatfoot from posterior tibial tendon dysfunction is felt around the navicular and along the medial longitudinal arch; and Achilles tendinopathy centers on the tendon near the heel — each with a distinct pain location. That said, Lisfranc arthrosis can coexist with progressing adult flatfoot, so differentiation requires careful clinical mapping of tenderness, weight-bearing radiographs to evaluate joint-space narrowing, osteophytes, and the alignment between the base of the second metatarsal and the intermediate cuneiform, and MRI when indicated to check cartilage status and bone marrow edema.

Distinguishing from Acute Trauma

Acute Lisfranc injury (fracture-dislocation from sports or falls) presents with marked swelling, subcutaneous hematoma, and inability to bear weight; if neglected, serious long-term sequelae follow, so urgent orthopedic evaluation and surgical decision-making take priority. This is fundamentally different from chronic Lisfranc arthrosis, and stem cell conditioned media joint injection should not be casually applied at this phase.

What Stem Cell Conditioned Media Joint Injection Can and Cannot Target

Behind the chronic pain of Lisfranc arthrosis lies a cascade in which chronic intra-articular synovitis persistently releases inflammatory cytokines such as IL-1β and TNF-α. Stem cell conditioned media contains anti-inflammatory cytokines and a spectrum of growth factors (TGF-β, IGF-1, VEGF, and others); intra-articular administration is expected to modulate the synovial inflammatory environment and lower the pain baseline. See details on our stem cell conditioned media joint injection here.

What It Can Target (Modulating the Intra-articular Inflammatory Environment)

– Attenuating the chronic pain cycle driven by intra-articular synovitis

– Reducing activity-dependent pain, first-step morning pain, and push-off pain, improving daily activity

– Positioning as a conservative option that may reduce the frequency of repeated steroid injections or serve as an alternative

What It Cannot Target (Bony Deformity and Malalignment)

– Physical removal of the osteophytes themselves

– Anatomical restoration of joint-space narrowing and cartilage defects

– Correction of bony prominence at the base of the second metatarsal or malalignment

These are hard to improve with conservative care; in advanced cases with prominent deformity, comparison with orthopedic surgery such as arthrodesis becomes appropriate. For general information on joint disease, please also refer to guidelines and materials from the Japanese Orthopaedic Association.

Treatment Design and Combination Strategy

When considering injection therapy for tarsometatarsal arthrosis, the injection should not stand alone. The foundation includes (1) insoles that double-support both the longitudinal and transverse arches, (2) a switch to shoes with a firm arch and rocker sole to assist push-off, (3) weight management, and (4) rehabilitation of the intrinsic foot muscles, triceps surae, and posterior tibial tendon. At our clinic, we evaluate objective changes in pain scores (NRS or VAS), gait pain, and daily activity at four to six weeks after the initial injection, and depending on the response, we decide whether to proceed with a two-to-three-injection series or refer to an orthotics clinic or orthopedic surgeon (including surgical assessment). The design is not “the more injections, the more cartilage returns.” The goal is to modulate the intra-articular environment, lower the pain baseline, and preserve the patient’s ability to continue with orthotics and rehabilitation.

Frequently Asked Questions

Q. Once I am diagnosed with Lisfranc joint osteoarthritis, when should I consider stem cell conditioned media joint injection?

First, diagnosis is confirmed with weight-bearing radiographs, clinical examination, and MRI when indicated, and the conservative foundation — insoles, footwear, weight management, and rehabilitation — is built. The realistic window for considering stem cell conditioned media joint injection is when activity-related pain persists despite this foundation and the patient is stuck in a cycle of repeated steroid injections or NSAID courses. In advanced end-stage cases with severe joint destruction and severe gait limitation, comparison with surgical options such as arthrodesis is required.

Q. I heard the Lisfranc complex has five joints. Which one is injected?

As a rule, we inject selectively under ultrasound guidance into the joint with the strongest clinical tenderness and imaging findings. In most cases, this is the second tarsometatarsal joint, but pain can extend to the lateral fourth and fifth tarsometatarsal joints, and the target joint is decided case by case. Under aseptic technique with a fine-gauge needle, the injection design balances intra-articular delivery rate with safety.

Q. Does one injection work? How many are typically needed?

Responses vary between individuals. To assess intra-articular anti-inflammatory effect, we evaluate objective changes in pain score, gait pain, and daily activity four to six weeks after the initial injection and consider additional injections as needed. When response is limited, we revisit the protocol or switch options. This is not a treatment where “the more you inject, the more cartilage returns.”

Q. Between surgery (arthrodesis) and stem cell conditioned media joint injection, which is better?

The two have different aims. Arthrodesis is surgery for advanced end-stage cases with severe deformity and instability, sacrificing joint motion to obtain pain relief and gait stability. Stem cell conditioned media joint injection for tarsometatarsal arthrosis is a conservative option that preserves joint motion while modulating the intra-articular inflammatory cycle, positioned mid-course. The question is not “which is better” but “which is appropriate for the current stage,” decided by examination and imaging.

Q. Can I continue sports and exercise with Lisfranc joint osteoarthritis?

It depends on the stage and severity of pain. Repeated midfoot impact from jogging, sprinting, or jumping can worsen pain and synovitis, so temporary adjustment is necessary. On the other hand, swimming, cycling, and walking on flat ground place less impact on the joint and can be continued in combination with rehabilitation of the triceps surae and intrinsic foot muscles. Individual exercise load is prescribed after examination.

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Supervising Physician: Shin Moriwaki, MD

Member, Japan Society of Aesthetic Surgery (JSAS) / Member, American Academy of Aesthetic Medicine

ECFMG Certificate (US Medical License Qualification)

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