Abstract
Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), impairs long-term potentiation (LTP) in hippocampus, a synaptic model of memory, while in spinal dorsal horn TNF-α is found to induce LTP of C-fiber evoked field potentials in rats with nerve injury. In the present work the role of IL-1β in the spinal LTP of C-fiber evoked field potentials, which is important for pathological pain, was investigated in both physiological and pathological conditions. We found that spinal application of IL-1β at the concentrations up to 500 ng/ml affected neither basal synaptic transmission mediated by C-fiber nor spinal LTP induced by tetanic stimulation in intact rats. In rats with neuropathic pain produced by spared nerve injury (SNI) or lumbar 5 ventral root transection (L5 VRT), however, IL- 1β at a low concentration (5 ng/ml) induced LTP of C-fiber evoked field potentials. Pretreatment with either p38 MAPK inhibitor (SB203580) or NF-κB inhibitor (PDTC) but not with JNK inhibitor (SP600125) completely blocked LTP induced by IL-1β in SNI rats. Taken together, the results indicated that exogenous IL-1β might induce spinal LTP only in rats with nerve injury but not in intact rats. The differential effects of proinflammatory cytokines on synaptic plasticity in spinal dorsal horn and in hippocampus may be clinically significant.
Highlights
Long-term potentiation (LTP) of synaptic transmission, which was first observed in hippocampus [1], has been intensively studied as a synaptic model of learning and memory [2]
We found that spinal application of IL-1 at the concentrations up to 500 ng/ml affected neither basal synaptic transmission mediated by C-fiber nor spinal long-term potentiation (LTP) induced by tetanic stimulation in intact rats
Recently we have shown that spinal application of TNF- does not affect spinal LTP induced by electrical stimulation in naïve animals but induces LTP in rats with nerve injury via activation of p38 MAPK, JNK and NF-B [25]
Summary
Long-term potentiation (LTP) of synaptic transmission, which was first observed in hippocampus [1], has been intensively studied as a synaptic model of learning and memory [2]. LTP has been demonstrated in other parts of central nervous system, such as, in spinal dorsal horn LTP of C-fiber evoked field potentials is induced by electrical tetanic stimulation of afferent C-fibers [3] and by nerve injury [4]. Since C-fibers ( called pain fibers) conveys nociceptive signals to spinal dorsal horn and LTP of C-fiber evoked synaptic responses occurs primarily in the synapses between afferent C-fibers and the second order projection neurons in superficial lamina [5], the long-lasting enhancement of synaptic transmission is considered as a form of pain memory [6, 7]. Activation of either TrkB receptor or dopamine D1/D5 receptor induces LTP in both hippocampus
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