"Induction of long-term potentiation in dorsal horn neurons and expression of immediate early genes Zif and Arc

Abstract

Abstract

Increased pain response following injury is an important step in the process of protecting the injured site from further damage. However, pain can often be a more serious problem than the injury or disease process that initiated it. In postoperative-, neuropathic- and chronic inflammatory pain, the pain often causes long lasting suffering for the patients, without any clear adaptive function.

Increased sensitivity to stimuli may be a result of not only the activity in the primary afferent fibers, but also functional changes within the CNS, i.e. central sensitization. In central sensitization, responses to stimulation of sensory receptors are enhanced without any change in excitability of the primary afferent neurons. One form of central sensitization may be spinal long-term potentiation (LTP).

In this project, electrophysiological recordings of single cell activity was performed before and after LTP induction in dorsal horn neurons by high frequency stimuli (HFS) conditioning. Quantitative real-time RT-PCR was used to examine whether the induction of spinal LTP was associated with changes in expression of two immediate early genes (IEG), i.e. Zif and Arc. The LTP-associated Zif and Arc expression was measured at three time points, immediately after surgery, 30 minutes after HFS and 120 minutes after HFS.

HFS-induced LTP in dorsal horn neurons outlasted the duration of the experiments (2-6 hours). Zif showed an approximately twofold increase of expression 120 minutes after HFS, suggesting the involvement for this transcription factor in the transition from early- to late-phase LTP. The expression of Arc however, was not altered following the stimulation. It is concluded that Zif, but not Arc, is upregulated in spinal cord neurons in association with HFS-induced LTP, indicating a role for this gene in the transition from early- to late-phase LTP.