Spinal cord stimulation analgesia: substantiating the mechanisms for neuropathic pain treatment.

The use of neuromodulation by electrical stimulation of the peripheral or central nervous system for the treatment of pain has been around for a long time, beginning with the use of electric eels thousands of years ago. Our modern understanding of the mechanisms of electrical stimulation for pain relief comes from the gate control theory, according to which the selective stimulation of nonnociceptive afferents (Ab) inhibits nociceptive afferents (A∂ and C) by the activation of inhibitory interneurons in the substantia gelatinosa of the posterior horns of the spinal cord. Transcutaneous electrical nerve stimulation (TENS) was developed to trigger this endogenous analgesia by peripheral stimulation. The development of spinal cord stimulation (SCS) derives from the same basic mechanisms, but with a central stimulator. Spinal cord stimulation consists of implantation of periepidural electrode in the posterior columns of the spinal cord at the spinal level of the dermatomes onwhich wewant to produce the analgesic effect. The mechanism of function of SCS is based on the same neurophysiological postulate as TENS. However, unlike TENS, the fact that the stimulation is applied directly to the posterior horns of the spinal cord does not allow us to conclude on the specific neurophysiological mechanisms of this analgesia. The stimulation may recruit afferents from the periphery, afferents from the spinal cord to the higher centers, local neuron circuits, andeven fibers of the anterior horns of the spinal cord. Spinal cord stimulations have been used for different types of pain with moderate success; a little more than 50% of the patients achieve pain relief of approximately 50%. We have to place these results in the context that SCS is commonly an end-of-the-road approachwhere conventional treatments have failed. It is suggested that patient selection is one of the burdens of SCS success. Most of the patient selection criteria are designed around exclusion criteria such as psychological problems, or inclusion criteria such as SCS trials with externalized electrodes to test for a good paresthesia and pain relief before the implant. However, even when controlling for several factors such as pain location, history of surgery, initial level of pain, litigation/worker’s compensation, age, gender, duration of pain, duration of follow-up, publication year, continent of data collection, study design, quality score, method of SCS lead implant, and type of SCS lead, the outcomes are still around 50% pain relief for 50% of the patients. Probably the most important factor in predicting the efficacy of SCS and in selecting patients who are the best responders is to try to establish a relation between the mechanisms of SCS analgesia and identification of the neurophysiological mechanisms implicated in a specific chronic pain condition. For instance, the use of spinal (nociceptive reflexes—RIII) and cortical activity (somatosensory-evoked potentials [SEP]) permitted investigators to demonstrate that reduced RIII and preserved SEP activity (no deafferentiation) are very good indicators of the success rate of SCS. Using similar procedures, another group of researchers came to the conclusion that SCS has spinal, supraspinal, and sympathetic effects on both nociceptive and nonnociceptive afferences. The results from these and other studies on the neurophysiological mechanisms of SCS are important in helping us to better characterize whether or not a patient with a specific deficit (eg, different types of neuropathic pain) is potentially a good responder to SCS. Interestingly, recent research on the identification of the mechanisms implicated in different chronic pain conditions supports the importance of excitatory (temporal summation [TS]) vs inhibitory (conditioned pain modulation [CPM]) mechanisms in identifying who is likely to be a responder to specific pharmacological treatments. For instance, TS but not CPM, is a good predictor for the clinical successof an anticonvulsant (pregabalin) in chronic pancreatitis, whereas a decreased CPM was a good predictor of the efficacy of an antidepressant (duloxetine). These results need replication, but are good indications that using relatively simple psychophysical approaches to identify the mechanisms implicated in chronic pain conditions may lead to a more rapid and adequate treatment selection. That is exactly what Eisenberg et al. have done in their study. Their project aimed at measuring the effect of SCS on central sensitization by measuring TS in patients with neuropathy using SCS for their chronic pain condition. Their hypothesis is derived from animal models that demonstrate that SCS was effective in reducing wide-dynamic-range neurons’ activity that is known to be implicated in central sensitization of neuropathic pain.