Repetitive noxious stimulation of unmyelinated C-fibres can result in prolonged discharge of dorsal horn cells. This phenomenon, termed "wind-up", is a progressive increase in the number of action potentials elicited per stimulus that occurs in dorsal horn neurons.
Repetitive episodes of "wind-up" may precipitate long-term potentiation (LTP), which involves a long-lasting increase in the efficacy of synaptic transmission. Where "wind-up" is thought to last only minutes, LTP lasts at least 1 hour and maybe even months. Both "wind-up" and LTP are believed to be part of the sensitisation process involved in many chronic pain states.
Animal studies suggest that expansion of receptive fields may also occur following tissue injury. Therefore, any peripheral stimulation would activate a greater number of dorsal horn cells because of an increased overlap of their receptive fields. Further evidence suggests that excessive nociceptive input to the dorsal horn can have excitotoxic consequences, resulting in the death of inhibitory interneurones. This inhibition may contribute to spinal hyperexcitability.
The allodynia and hyperalgesia associated with neuropathic pain may be due to the following:
The development of spontaneous activity of afferent input
The sprouting of large primary efferents (e.g. A-beta fibres from lamina III into lamina I and II)
Sprouting of sympathetic efferents into neuromas and dorsal root and ganglion cells
Elimination of intrinsic modulatory systems
Upregulation of receptors in the dorsal horn which mediate excitatory processes.
The central nervous system plastic changes appear to be associated with enhanced neurotransmission via the NMDA (N-methyl-D-aspartate) receptor. Under the appropriate conditions, appropriate C-fibre stimulation can activate dorsal horn interneurones, causing them to release excitatory amino acids (e.g. aspartate and glutamate), which will excite wide dynamic range (WDR) neurones via the NMDA receptor.