Peripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy

Patients with painful neuropathy frequently complain of pain in response to normally non-painful brushing, namely dynamic mechanical allodynia. Despite many animal studies suggesting that allodynia arises when the spontaneous firing in damaged nociceptive afferents sensitise second-order nociceptive neurons to Aβ-fibre input, no studies have sought to confirm this mechanism by investigating Aβ-fibre sparing in human patients with allodynia. In this study we compared data from Aβ-fibre-mediated nerve conduction studies and nociceptive-fibre-mediated laser-evoked potentials (LEPs) in 200 patients with distal symmetric polyneuropathy (114 with neuropathic pain, 86 without). Of the 114 patients with painful neuropathy studied, 44 suffered from allodynia. Whereas no statistical difference was found in nerve conduction study data between patients with and without allodynia, LEP amplitudes were larger in patients with allodynia than in those without (P < 0.01 by Mann-Whitney U test). The lack of difference in NCS data between patients with and without allodynia suggest that this type of pain, rather than arising through second-order nociceptive neuron sensitization to Aβ-fibre input, might reflect a reduced mechanical threshold in sensitised intraepidermal nociceptive nerve terminals.