Pipette 23.6.13 free downloads: Understanding MIF-Induced Hyperexcitability in Spinal Cord Injury

Spinal cord injury (SCI) can lead to chronic hyperexcitability, characterized by ongoing electrical activity that contributes to neuropathic pain. However, research has shown that macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models, may also play a role in this process.

Unlike chronic SCI-induced hyperexcitability, acute MIF-induced hyperexcitability was only partially abrogated by inhibiting ERK signaling. This suggests that there are multiple mechanisms contributing to the development of neuropathic pain after SCI.

In fact, studies have shown that MIF can stimulate affective pain, and conditioned behavioral aversion to a chamber associated with peripheral MIF injection supports this notion. Furthermore, probable nociceptors isolated from male rats and exposed to an MIF concentration reported in human plasma (1 ng/ml) showed hyperactivity similar to that induced by SCI.

Interestingly, a 10-fold higher concentration of MIF failed to increase excitability in these neurons, suggesting that there may be a threshold effect for MIF-induced hyperexcitability. This finding highlights the complexity of the mechanisms underlying neuropathic pain after SCI.

People living with SCI exhibit acute and chronic elevation of circulating levels of MIF, which raises questions about whether extrinsic chemical signals contribute to ongoing electrical activity after SCI. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain.

While SCI pain mechanisms are often assumed to be primarily mediated by central nervous system (CNS) processes, rodent studies have revealed important mechanistic contributions from primary nociceptors. Therefore, targeting MIF and other peripheral factors may offer novel therapeutic strategies for managing neuropathic pain after SCI.

Overall, understanding the role of MIF-induced hyperexcitability in spinal cord injury is crucial for developing effective treatments for this debilitating condition. By exploring the complex interplay between CNS and peripheral mechanisms, researchers can identify new targets for therapy and improve outcomes for individuals living with SCI.