UBC Faculty Research and Publications

Long-term actions of interleukin-1β on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization Gustafson-Vickers, Sabrina L; Lu, Van B; Lai, Aaron Y; Todd, Kathryn G; Ballanyi, Klaus; Smith, Peter A


Background: Cytokines such as interleukin 1β (IL-1β) have been implicated in the development of central sensitization that is characteristic of neuropathic pain. To examine its long-term effect on nociceptive processing, defined medium organotypic cultures of rat spinal cord were exposed to 100 pM IL-1β for 6–8 d. Interleukin effects in the dorsal horn were examined by whole-cell patch-clamp recording and Ca²⁺ imaging techniques. Results Examination of the cultures with confocal Fluo-4 AM imaging showed that IL-1β increased the change in intracellular Ca²⁺ produced by exposure to 35–50 mM K⁺. This is consistent with a modest increase in overall dorsal horn excitability. Despite this, IL-1β did not have a direct effect on rheobase or resting membrane potential nor did it selectively destroy any specific neuronal population. All effects were instead confined to changes in synaptic transmission. A variety of pre- and postsynaptic actions of IL-1β were seen in five different electrophysiologically-defined neuronal phenotypes. In putative excitatory 'delay' neurons, cytokine treatment increased the amplitude of spontaneous EPSC's (sEPSC) and decreased the frequency of spontaneous IPSC's (sIPSC). These effects would be expected to increase dorsal horn excitability and to facilitate the transfer of nociceptive information. However, other actions of IL-1β included disinhibition of putative inhibitory 'tonic' neurons and an increase in the amplitude of sIPSC's in 'delay' neurons. Conclusion Since spinal microglial activation peaks between 3 and 7 days after the initiation of chronic peripheral nerve injury and these cells release IL-1β at this time, our findings define some of the neurophysiological mechanisms whereby nerve-injury induced release of IL-1β may contribute to the central sensitization associated with chronic neuropathic pain.

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