The Potential Role of SI00B and Brain Derived Neurotrophic Factor in Predicting Outcome From Using Pulsed Radiofrequency in Treatment of Patients With Lumbar Disc Prolapsed

Chronic lumbar radicular (CLR) pain is a term used to describe neuropathic pain symptoms in the distribution of a particular lumbar nerve root due to disc protrusion, spinal stenosis, facet hypertrophy, or fibrosis after previous surgery. The pathophysiology of CLR pain involves mechanical, inflammatory, and immunologic factors that affect the function of the dorsal root ganglion (DRG).1Treatment methods include oral pain medications, physical therapy, epidural steroid injection (ESI) and surgery. 2,3.

Pulsed radiofrequency (PRF) was developed as a modification of the well-known radiofrequency ablation treatment. In conventional radiofrequency ablation, a high frequency alternating current is used to produce coagulative necrosis of the target nerve tissue without any selectivity for nociceptive fibers. However, in PRF, a current in short (20 msec) high voltage bursts is followed by silent phases (480 msec) which allow for heat dissemination, keeping the target tissue controlled below 42°C. 4,5 The mechanisms via which PRF causes analgesia are still not clearly understood, but laboratory experiments have highlighted some possible ways in which it might act, including its effects on neuropathic pain. Clinical use of PRF has been expanding, despite there being limited evidence of clinical efficacy in the form of randomized controlled trials (RCTs). 6 There have been few RCTs using PRF-DRG for radicular pain. Van Zundert et al performed an RCT in subjects with cervical radicular pain.7 Simopoulos et al did a pilot study on lumbar radicular pain, but the methodology included application of conventional radiofrequency over PRF in the study group and was not an efficacy trial. As such, the efficacy of PRF-DRG in CLR has never been determined. 8

Neuroplasticity or neuronal plasticity refers to the ability of the nervous system to do neuronal remodeling, formation of novel synapses and birth of new neurons. Neuronal plasticity is intimately linked to cellular responsiveness and may therefore be considered an index of the neuronal capability to restore its function. Failure of such mechanisms might enhance the susceptibility to neuronal injury.9 Neurotrophic factors (NTFs), and in particular the neurotrophin family, play an important role. In fact, besides their classical role in supporting neuronal survival, NTFs finely modulate all the crucial steps of network construction, from neuronal migration to experience-dependent refinement of local connections. It is now well established that NTFs are important mediators of neuronal plasticity also in adulthood where they modulate axonal and dendritic growth and remodeling, membrane receptor trafficking, neurotransmitter release, synapse formation and function.10 The neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as crucial mediator of neuronal plasticity, suggesting that it might indeed bridge experience with enduring change in neuronal function.11BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses.12,13 S100B belongs to the family ofcalcium binding proteins, is expressed mainly by astrocytesand is found both intra- and extracellularly in brain tissue. It was also reported that mature myelinating and non-myelinating Schwann cells of peripheral nerves strongly display S100 protein immunoreactivity (Stefansson et al., 1982; Sugimura et al., 1989; Vega et al., 1996).14 S100B can spill from injured cells and enter the extracellular space or bloodstream. Serum levels of S100B increase in patients with neuronal damage. Over the last decade, S100B has emerged as a candidate peripheral biomarker of neuronal injury. Elevated S100B levels accurately reflect the presence ofneurodegenerayion. Its potential clinical use in the therapeutic decisions is substantiated by a vast body of literature. Thus, the major advantage of using S100B is that its elevatio in serum provides a sensitive measure for determining neuronal injury at the molecular level before gross changes level.15