The potential role of nerve growth factor (NGF) in painful neuromas and the mechanism of pain relief by their relocation to muscle.

Painful neuromas have been successfully treated by surgical procedures including relocation to muscle, but the underlying molecular mechanism remains unclear. Nerve growth factor (NGF) is secreted by tissues and promotes the expression of ion channels and neuropeptides in sensory neurons involved in pain transmission. We hypothesised that excess of NGF may lead to pain in neuromas and that the efficacy of surgical relocation results from deprivation of NGF, i.e. translocation from NGF-rich regions, particularly sub-cutaneous structures associated with injury or inflammation, to NGF-poor structures such as muscle or bone. Using immunohistological methods with primary antibodies to rhNGF, we report that NGF levels were elevated in 13 painful neuromas in comparison with six control nerves. However, in four painful neuromata re-located into muscle with pain relief, the NGF level was similar to that of controls. NGF levels suggest an explanation for the development of painful neuromas and the efficacy of relocation.

Correlation of nerve root pain with dermatomal sensory threshold and back pain with spinal movement in single level lumbar spondylosis.

We studied 27 patients with low back pain and unilateral L5 or S1 spinal nerve root pain. Significant radiological changes were restricted to the symptomatic root level, when compared with controls. Low back and leg pain were graded on a visual analogue scale. Dermatomal quantitative sensory tests revealed significant elevations of warm, cool and touch perception thresholds in the affected dermatome, compared with controls. These elevations correlated with root pain (warm v L5 root pain; r = 0.88, p < 0.0001), but not with back pain. Low back pain correlated with restriction of anteroposterior spinal flexion (p = 0.02), but not with leg pain. A subset of 16 patients underwent decompressive surgery with improvement of pain scores, sensory thresholds and spinal mobility. A further 14 patients with back pain, multilevel nerve root symptoms and radiological changes were also studied. The only correlation found was of low back pain with spinal movement (p < 0.002). We conclude that, in patients with single level disease, dermatomal sensory threshold elevation and restriction of spinal movement are independent correlates of sciatica and low back pain.

Influence of human skin injury on regeneration of sensory neurons.

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.