Fig 6.

Alterations in skin innervation can be used to categorize neuropathic pain syndromes of diverse aetiologies. (a) Innervation of the skin serves to protect organisms through normal nociception. Growth factors (e.g. NGF and GDNF) are constantly produced in the skin and transported retrogradely to sensory neurone cell bodies. (b) When cell bodies are lost or nerves cut and cannot regrow (‘static’ denervation neuropathies), reduced cutaneous innervation results in intact sensory fibres being exposed to abnormally high levels of neurotrophins; this hypertrophic microenvironment is known to enhance excitability and promote sprouting. (c) In ‘dynamic’ denervation neuropathies, cyclic metabolic or other types of stress render cell bodies unable to maintain their longest axons. During cycles of retraction and regrowth, pro-inflammatory cytokines or other mediators may produce axonal excitation. In addition, intact nerve terminals are subject to a hypertrophic environment. (d) In a class of neuropathies or ‘dynias’ best exemplified by vulvodynia or Gullian–Barré syndrome (GBS), immune system activation (or perhaps other factors) have caused local regions of hyperinnervation by cutaneous nociceptors and these nerve terminals display hyperexcitability.