Stimulation-induced expression of immediate early gene proteins in the dorsal horn is increased in neuropathy

Abstract

Neuropathic pain following nerve injury may have clinical maniestations such as hyperalgesia, allodynia and spontaneous pain [1]. his can be a result of hyperexcitability in peripheral nerve fibres, ut may also involve induction of long-term potentiation (LTP) in he CNS. In this issue of the Scandinavian Journal of Pain, Bojovic and oworkers address the possible role of changes in the immediate arly gene proteins (IEGPs) Arc, Zif268 and c-Fos expression in the orsal horn during neuropathic pain following noxious conditionng stimulation of the sciatic nerve [2]. The aim of the study was to ompare the effect of this noxious conditioning in neuropathic rats ersus non-neuropathic rats. Previously, Bojovic and coworkers have shown that the noxious onditioning changes the expression of the IEGP mentioned above 3], as well as induce spinal cord LTP [4]. Earlier data suggest that the TP phenomenon induced by noxious stimuli represents a cellular emory of nociceptive information. Several lines of evidence show hat extracellular signal-regulated kinase (ERK) is activated in the orsal horn neurons following noxious sciatic nerve stimulation 5]. ERK can be translocated to the nucleus where it activates the AMP element binding protein (CREB), which in turn stimulates ranscription by binding to the regulatory cAMP response element CRE). Many IEGPs including Arc, Zif268 and c-Fos may be induced y the ERK-CREB pathway. The IEGP responses are complex and may include induction f many different transcription factors as well as growth factors, ignalling enzymes, phosphatases and structural proteins. Since the ate-phase LTP in the dorsal horn may be blocked by protein synhesis inhibitors [6], it seems likely that maintenance of LTP in the pinal cord involves de novo protein synthesis. A primary nuclear vent in this process may be the induction of IEGs. Evidence exists hat peripheral inflammation also increases the expression of the RE-containing IEGs in the spinal cord [7]. The results of Bojovic and coworkers showed that Arc, Zif268 nd c-Fos exhibited a significant increase in the dorsal horn mmunoreactivity the first hours after the sciatic conditioning comared with time-matched, sham operated controls. As in previous eports [3], the authors show that maximal IEGP expression may be