Nociception at the diabetic foot, an uncharted territory

Abstract

The diabetic foot is characterised by painless foot ulceration and/or arthropathy; it is a typical complication of painless diabetic neuropathy. Neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres, which are mostly nociceptors and excitable by noxious stimuli only. However, some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported. Hence, it is well established by quantitative sensory testing that thermal detection thresholds at the foot skin increase during the course of painless diabetic neuropathy. Pain perception (nociception), by contrast, has rarely been studied. Recent pilot studies of pinprick pain at plantar digital skinfolds showed that the perception threshold was always above the upper limit of measurement of 512 mN (equivalent to 51.2 g) at the diabetic foot. However, deep pressure pain perception threshold at musculus abductor hallucis was beyond 1400 kPa (equivalent to 14 kg; limit of measurement) only in every fifth case. These discrepancies of pain perception between forefoot and hindfoot, and between skin and muscle, demand further study. Measuring nociception at the feet in diabetes opens promising clinical perspectives. A critical nociception threshold may be quantified (probably corresponding to a critical number of intraepidermal nerve fibre endings), beyond which the individual risk of a diabetic foot rises appreciably. Staging of diabetic neuropathy according to nociception thresholds at the feet is highly desirable as guidance to an individualised injury prevention strategy.

Keywords: Amputation; Diabetes mellitus; Diabetic neuropathy; Foot ulcer; Insensitivity to pain; Neuroarthropathy; Pain perception.

Figure 1

Sketch reproduced from Brand P[2].

Figure 2

Intraepidermal nerve fibre ending density at the lower limb in relation to severity of diabetic neuropathy (adapted from Quattrini et al[41]). HC: Healthy controls; DC: Diabetic controls; Dmi: Mild SDN; Dmo: Moderate SDN; Dsev: Severe SDN; SDN: Symptomatic diabetic neuropathy; INEF: Intraepidermal nerve fibre ending.

Figure 3

MSA Thermotest^® (electronic device, expensive!).

Figure 4

Algometer^® (electronic device, expensive!).

Figure 5

MARSTOCKnervtest^® PinPrick stimulator 512 mN (fibreglass, cheap!).

Figure 6

Pressure pain perception threshold measurements done in own studies[61]. CPPPT: Cutaneous pressure pain perception threshold; DPPPT: Deep pressure pain perception threshold.

Figure 7

Lowered pain perception thresholds (hyperalgesia) after acute skeletal trauma of the foot in 13 healthy control subjects (sprain, toe fracture) and in 12 diabetic foot patients (elective surgery) at the injured site. Data are combined from ref. [59,61]. A: Cutaneous pressure pain perception threshold (mN) (pinprick) at plantar digital skinfold (medians); B: Deep pressure pain perception threshold (kPa) over metatarsophalangeal joint (medians); C: Deep pressure pain perception threshold (kPa) over musculus abductor hallucis (medians).