Recently, the successful implementation of promising therapies that do not rely on paresthesia such as Burst SCS (B-SCS), high frequency SCS (HF-SCS) and differential target multiplexed SCS, has challenged the fundamental gate control theory. 15 Additionally, Vallejo’s group published an optimized algorithm of stimulation that is able to shift glial cell gene expression to a naïve phenotype after sciatic nerve ligation model in rodents.
14 Preliminary work by Vallejo et al on differential target multiplexed SCS (DTM-SCS) and an user-adaptive and effective SCS model has shown promising results. 13 Moreover, significant reduction in CSF concentrations of pro-inflammatory molecules including interleukin (IL) 1, IL-6, tumor necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF) have been described after spinal cord stimulation (SCS). 11, 12 In a cross-sectional clinical study, Bäckryd et al reported a significant increase of chemokines levels in cerebrospinal fluid (CSF) of patients with neuropathic pain when compared to healthy controls. 10Ĭytokines are involved in several nervous system biological processes including neurogenesis, neuron outgrowth, neural survival, and synaptic pruning, transmission and plasticity. 9 Therefore, early stimulation devices have been continuously updated with adaptive programming and a wide array of new lead placements, frequencies and stimulation patterns. 8 Conventional SCS devices were able to elicit paresthesia through electrical stimulation of the dorsal columns and, since their inception, technical complexity has grown exponentially. Melzack and Wall originally proposed the gate control theory of pain which led to the current description of the SCS mechanisms of action. Initially, the development of novel therapeutic approaches for patients experiencing nociceptive and/or neuropathic chronic pain was driven by the necessity to avoid long-term side effects resulting from the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid therapies.
However, the impact of these neuroimmune and neuroinflammatory responses on the onset of acute pain and its transition to chronic entities in humans is yet to be determined. 6 Both mechanisms have been widely studied in animals laying the groundwork for specific pain therapies in humans. 4, 5 Preclinical evidence has identified neuroimmune and inflammatory neuromodulatory responses in the nervous system (eg pathological activation of microglia and astrocytes in the spinal cord) as two of the major contributors to pain pathogenesis and persistence. Glial cells such as microglia, oligodendrocytes, astrocytes, and ependymal cells have shown to alter activity and gene expression when exposed to physiological stressors, including nerve damage. Neuroinflammation, including alteration of glial cells function following nerve injury or gliosis, has emerged as a promising mechanism triggering the transition to chronic back pain. Chronic low back pain (LBP) comprises a heterogeneous group of disorders including, but not limited to, persistent spinal pain syndrome and radicular pain.
1, 2 Undoubtedly, chronic pain results in a significant physical, psychological, emotional and economic burden for patients. Chronic pain is a well-known clinical entity affecting a substantial proportion of the general population.