Why do fractures hurt more a couple of days after the initial injury?

Why Fractures Hurt More a Couple Days After Injury

Fractures typically hurt more 2-3 days after injury because the inflammatory response peaks during this period, causing increased swelling, tissue hypoxia, acidosis, and release of pro-inflammatory mediators that sensitize pain nerves. 1, 2, 3

The Inflammatory Timeline After Fracture

Initial Phase (0-72 hours)

• The inflammatory phase is characterized by progressive tissue damage that worsens over the first 72 hours, including swelling, contusion, and development of large avascularized zones around the fracture site 4
• Hypoxia (low oxygen) and acidosis develop throughout the injured region, creating a catabolic state that persists for at least 72 hours depending on injury severity 4
• The inflammatory response involves migration of immune cells and release of active molecules that directly stimulate pain receptors 3

Peak Pain Period (Days 2-4)

• Pain intensification occurs as pro-inflammatory cytokines, growth factors, and other mediators accumulate at the fracture site, directly sensitizing nerve terminals 2, 3
• Mechanical distortion of somatosensory nerve terminals in bones and surrounding muscles is compounded by chemical irritation from inflammatory mediators 2
• Swelling reaches its maximum during this period, causing additional mechanical pressure on pain-sensitive structures 5

Biological Mechanisms Driving Increased Pain

Neuroinflammatory Response

• The inflammatory cascade releases chemokines, proinflammatory mediators, and neurotransmitters that enhance pain signaling through both peripheral sensitization and central nervous system changes 2
• Microglial activation in the spinal cord contributes to central sensitization, amplifying pain signals beyond the initial injury 2
• This process involves excitatory synaptic plasticity that can trap patients into persistent pain states 2

Cellular and Molecular Events

• Osteoprogenitor cells, mesenchymal cells, osteoblasts, and chondrocytes migrate to the injury site and contribute to both healing and the inflammatory response 3
• The transforming growth factor-beta superfamily, metalloproteinases, and angiogenic factors are released, all of which modulate pain perception 3
• Low oxygen tension and impaired perfusion at the fracture site create conditions that perpetuate inflammatory signaling 3

Clinical Implications for Pain Management

Expected Timeline

• Minor swelling is physiological and typically disappears within the first week, but pain may persist or worsen during days 2-4 before gradually improving 5
• Persistent swelling beyond 1 week requires evaluation for complications such as outflow obstruction, hematoma, infection, or venous hypertension 5

Early Callus Formation

• Early callous formation begins within the first week of injury, which is why surgical interventions become technically more difficult after 72 hours 6, 7
• This early healing response paradoxically contributes to pain as new bone formation involves periosteal irritation 6

Common Pitfalls to Avoid

• Do not dismiss worsening pain at 2-3 days as abnormal—this is the expected peak of the inflammatory response 1, 2, 3
• However, unremitting pain during follow-up warrants reevaluation for potential complications such as compartment syndrome, infection, or inadequate fracture stabilization 5, 8
• Patients should be counseled that this delayed pain increase is normal and does not indicate treatment failure or worsening of the fracture 5

The key distinction is between expected inflammatory pain (peaks days 2-4, then gradually improves) versus pathological pain (progressively worsens beyond day 4-7 or is associated with other concerning signs like fever, increasing swelling, or neurovascular compromise) 5, 2.