- Novel impulse generators develop at various sites, and these are not stimulus-dependent.
- In peripheral nerve, it has been shown that ectopic impulse generation (EIG) develops as a result of the expression of abnormal sodium channels. This can be modified by neurotrophic growth factors (a potential target for new treatments).
- Abnormal chemical sensitivities develop in damaged primary sensory neurons, notably to catecholamines. Whilst this can be readily demonstrated in experimental preparations, the clinical relevance remains uncertain.
- Degenerative and then regenerative changes in the spinal cord may lead to aberrant connectivity, and possibly a permanently reorganised, irreversible state.
- Damage at one level in the nervous system may lead to secondary pathophysiological changes at more rostral levels. This has important implications when targeting treatments for hyperpathia.
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