Although it is well known that diabetic neuropathy is an essential prerequisite for a diabetic Charcot foot (as well as for a painless diabetic foot ulcer), abnormalities of pain perception have received only little attention. Stevens et al. observed a series of 12 patients with acute Charcot foot, all of whom complained of ‘a dull deep ache’ in the foot. However, this symptom was not further addressed. Interestingly, 11 patients had preserved cutaneous pressure perception (although at an increased threshold) (18
). Frykberg, in a book chapter on the diabetic Charcot foot, mentioned the paradoxical ‘pain or aching in an otherwise insensate foot’ without further commentary (19
). Walking evokes this deep dull aching in an acute Charcot foot; it likely originates in bones, joints, ligaments, or epiligamentous structures (20
) in the tarsus rather than in other regions of the foot.
Modern techniques of quantitative sensory testing are available (8
) that allow us to study pain perception in the diabetic Charcot foot in more detail. Preliminary data show that the threshold for punctate pressure pain perception is extremely elevated in the skin of the plantar foot: stimulation with calibrated monofilaments at a force of 512 mN (the upper limit of measurement) will not evoke pain in 100% of diabetic patients with an ulcer or Charcot foot (9
). This finding suggests depletion of the skin from A-delta nociceptors. A-delta nociceptors may also degenerate at the musculoskeletal level, which may explain why patients with acute Charcot foot rarely recall a ‘first’ pain event (evoked by the trigger injury of the condition). The presence of C-fibers or A-delta fibers alone will signal a component of skeletal pain, but for the full intensity of fracture pain to develop it requires the presence and activation of both the A-delta and C-populations that normally innervate the bone (22
Most patients with an acute Charcot foot (18
) experience deep dull aching inside the foot when stepping on it. This pain sensation (‘second’ pain?), which palpation cannot evoke, and which is not observed in the case of an ulcer or osteomyelitis at a metatarsal head, is inappropriately mild in relation to the degree of inflammation, and to the magnitude of the blunt force applied on the injured foot. The pain resembles that of a stress fracture (fatigue fracture) or osteoarthritis, as it is insidious in onset, mild-to-moderate in intensity, worsened by use of the involved joint, and improved with rest (9
) – but it lacks a disabling character (24
). It is present in the inflamed stages 0, I, or II of the Charcot foot, but may also occur in stage III, when unprotected walking reactivates skeletal injury and inflammation (acute exacerbation of Charcot arthropathy).
The deep dull aching subsides by offloading and immobilizing the foot, corresponding to resolution of the inflammation. This suggests that the pain mechanism may be a faulty, incomplete hyperalgesia confined to injured skeletal structures, which lacks the contribution of skin nociception (skin hyperalgesia and allodynia (26
)) despite the profound inflammation (erythema, hyperthermia and swelling) of dermis and epidermis. This faulty skeletal hyperalgesia would probably require some living nociceptors in the tarsus, notably C-fiber nociceptors expressing TrkA (tropomyosin receptor kinase A, that is, the NGF receptor (27
)), which remains to be demonstrated in diabetic neuropathy. The hypothetic components of pain from mechanical stimulation at the foot in healthy people and patients with diabetic Charcot foot are summarized in .
Pain from mechanical stimulation in healthy versus Charcot feet