Dorsal Root Ganglion Stimulation Relieves Chronic Neuropathic Pain Along With a Decrease in Cortical γ Power.

BACKGROUND: Stimulation of dorsal root ganglion (DRG) is an ideal neuromodulative intervention, providing pain relief in localized chronic pain conditions because γ-band oscillations reflect the intensity of ongoing chronic pain in patients affected. OBJECTIVE: We aimed to observe the role of cortical γ-band power associated with the relief of chronic neuropathic pain through DRG stimulation (DRGS). MATERIALS AND METHODS: We examined nine patients (two women, mean age 56.8 years; range, 36-77 years) diagnosed with chronic neuropathic pain who underwent DRGS therapy. We used the numeric rating scale (NRS) on the painful limb and simultaneously recorded the electroencephalography to assess the broadband γ power. Assessments were conducted on the first day and on the seventh day after implantation of the DRGS system and then compared and correlated with the results of the NRS. RESULTS: The NRS scores showed a significant decrease from the first day to the seventh day (p = 0.007). The resting-state γ power revealed a significant decrease (p = 0.021) between 30 and 45 Hz, recorded through the central electrode contralateral to the painful limb from the first day (mean [M] = 0.46, SD = 0.25) to the seventh day (M = 0.31, SD = 0.12) after DRGS. There was no significant change in the resting-state γ-band power recorded through the central electrode ipsilateral to the painful limb. However, we found a positive correlation in the γ-band power (rs = 0.628, p = 0.005) with the NRS rating. CONCLUSIONS: A lateralized decrease in broadband γ power may be considered further evidence supporting a reduction in the hyperexcitability of the nociceptive system in response to DRGS therapy. In the future, γ-band power could serve as a biomarker for assessing the efficacy of DRGS during the seven-day test phase preceding the implantation of the DRGS system.

Non-invasive recording of high-frequency signals from the human spinal cord.

Throughout the somatosensory system, neuronal ensembles generate high-frequency signals in the range of several hundred Hertz in response to sensory input. High-frequency signals have been related to neuronal spiking, and could thus help clarify the functional architecture of sensory processing. Recording high-frequency signals from subcortical regions, however, has been limited to clinical pathology whose treatment allows for invasive recordings. Here, we demonstrate the feasibility to record 200-1200 Hz signals from the human spinal cord non-invasively, and in healthy individuals. Using standard electroencephalography equipment in a cervical electrode montage, we observed high-frequency signals between 200 and 1200 Hz in a time window between 8 and 16 ms after electric median nerve stimulation (n = 15). These signals overlapped in latency, and, partly, in frequency, with signals obtained via invasive, epidural recordings from the spinal cord in a patient with neuropathic pain. Importantly, the observed high-frequency signals were dissociable from classic spinal evoked responses. A spatial filter that optimized the signal-to-noise ratio of high-frequency signals led to submaximal amplitudes of the evoked response, and vice versa, ruling out the possibility that high-frequency signals are merely a spectral representation of the evoked response. Furthermore, we observed spontaneous fluctuations in the amplitude of high-frequency signals over time, in the absence of any concurrent, systematic change to the evoked response. High-frequency, "spike-like" signals from the human spinal cord thus carry information that is complementary to the evoked response. The possibility to assess these signals non-invasively provides a novel window onto the neurophysiology of the human spinal cord, both in a context of top-down control over perception, as well as in pathology.

Laser-evoked potentials recover gradually when using dorsal root ganglion stimulation, and this influences nociceptive pathways in neuropathic pain patients.

OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is able to relieve chronic neuropathic pain. There seems evidence that DRGS might achieve this by gradually influencing pain pathways. We used laser-evoked potentials (LEP) to verify our hypothesis that the recovery of the LEP may reflect DRGS-induced changes within the nociceptive system. METHODS: Nine patients (mean age 56.8 years, range 36-77 years, two females) diagnosed with chronic neuropathic pain in the knee or groin were enrolled in the study. We measured each patient's LEP at the painful limb and contralateral control limb on the first, fourth, and seventh day after implantation of the DRGS system. We used the numeric rating scale (NRS) for the simultaneous pain assessment. RESULTS: The LEP amplitude of the N2-P2 complex showed a significant increase on day 7 when compared to day 1 (Z = -2.666, p = 0.008) and to day 4 (Z = -2.547, p = 0.011), respectively. There was no significant difference in the N2-P2 complex amplitude between ON and OFF states during DRGS. The patients' NRS significantly decreased after 1 day (p = 0.007), 4 days (p = 0.007), and 7 days (p = 0.007) when compared to the baseline. CONCLUSIONS: The results show that with DRGS, the LEP recovered gradually within 7 days in neuropathic pain patients. Therefore, reduction of the NRS in patients with chronic neuropathic pain might be due to DRGS-induced processes within the nociceptive system. These processes might indicate neuroplasticity mediated recovery of the LEP.

Brain Computer Interfaces for Assisted Communication in Paralysis and Quality of Life.

The rapid evolution of Brain-Computer Interface (BCI) technology and the exponential growth of BCI literature during the past 20 years is a consequence of increasing computational power and the achievements of statistical learning theory and machine learning since the 1960s. Despite this rapid scientific progress, the range of successful clinical and societal applications remained limited, with some notable exceptions in the rehabilitation of chronic stroke and first steps towards BCI-based assisted verbal communication in paralysis. In this contribution, we focus on the effects of noninvasive and invasive BCI-based verbal communication on the quality of life (QoL) of patients with amyotrophic lateral sclerosis (ALS) in the locked-in state (LIS) and the completely locked-in state (CLIS). Despite a substantial lack of replicated scientific data, this paper complements the existing methodological knowledge and focuses future investigators' attention on (1) Social determinants of QoL and (2) Brain reorganization and behavior. While it is not documented in controlled studies that the good QoL in these patients is a consequence of BCI-based neurorehabilitation, the proposed determinants of QoL might become the theoretical background needed to develop clinically more useful BCI systems and to evaluate the effects of BCI-based communication on QoL for advanced ALS patients and other forms of severe paralysis.

Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level.

OBJECTIVES: Dorsal root ganglion stimulation (DRGS) has been used successfully against localized neuropathic pain. Nevertheless, the effects of DRGS on pain processing, particularly at the cortical level, remain largely unknown. In this study, we investigated whether positive responses to DRGS treatment would alter patients' laser-evoked potentials (LEP). METHODS: We prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months. LEPs were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS. RESULTS: At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p's < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10). CONCLUSIONS: DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity.

Dorsal Root Ganglion Stimulation Used for the Treatment of Chronic Neuropathic Pain in the Groin: A Single-Center Study With Long-Term Prospective Results in 34 Cases.

OBJECTIVE: Chronic neuropathic pain in the groin is a severe condition and difficult to treat. Dorsal root ganglion stimulation (DRGS) covers discrete painful areas precisely with its stimulation power in comparison to spinal cord stimulation (SCS). It was our hypothesis that DRGS provides a long-term relief of chronic groin pain over a period of more than three years. MATERIALS AND METHODS: Patients (age >18 years) with chronic neuropathic groin pain were prospectively examined. After a successful test-trial (duration of 3-10 days, pain decrease >50%) a permanent generator was implanted. The patients were re-examined after three months, then after one year, two, and three years. We used the Visual Analogue Scale (VAS), the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory (BPI), and the Beck Depression Inventory (BDI) for the assessment. RESULTS: We included 34 consecutive patients (13 female, 21 male, mean age 50.4 years, range of age 24-84 years, 30/34 trial to permanent conversion) during the time period from 2012 until 2016. Thirty patients had a successful test-trial and a generator was subsequently implanted. Results after three years: the preoperative VAS dropped from Mdn = 8 to Mdn = 4.5 (p = 0.001). The PDI decreased from Mdn = 48 to Mdn = 23 (p = 0.004). The PCS changed from Mdn = 31 to Mdn = 16 (p = 0.006). The BPI dropped from Mdn = 76 to Mdn = 30 (p = 0.003). The BDI decreased from Mdn = 17 to Mdn = 7 (p = 0.010). Five patients showed complications (16.7%). CONCLUSION: In this study, DRGS proved an efficient long-term method for the treatment of chronic neuropathic groin pain and we strongly recommend its use.

A computational model of neuro-glio-vascular loop interactions.

We present a computational, biophysical model of neuron-astrocyte-vessel interaction. Unlike other cells, neurons convey "hunger" signals to the vascular network via an intervening layer of glial cells (astrocytes); vessels dilate and release glucose which fuels neuronal firing. Existing computational models focus on only parts of this loop (neuron→astrocyte→vessel→neuron), whereas the proposed model describes the entire loop. Neuronal firing causes release of a neurotransmitter like glutamate which triggers release of vasodilator by astrocytes via a cascade of biochemical events. Vasodilators released from astrocytic endfeet cause blood vessels to dilate and release glucose into the interstitium, part of which is taken up by the astrocyticendfeet. Glucose is converted into lactate in the astrocyte and transported into the neuron. Glucose from the interstitium and lactate (produced from glucose) influx from astrocyte are converted into ATP in the neuron. Neuronal ATP is used to drive the Na(+)/K(+)ATPase pumps, which maintain ionic gradients necessary for neuronal firing. When placed in the metabolic loop, the neuron exhibits sustained firing only when the stimulation current is more than a minimum threshold. For various combinations of initial neuronal [ATP] and external current, the neuron exhibits a variety of firing patterns including sustained firing, firing after an initial pause, burst firing etc. Neurovascular interactions under conditions of constricted vessels are also studied. Most models of cerebral circulation describe neurovascular interactions exclusively in the "forward" neuron→vessel direction. The proposed model indicates possibility of "reverse" influence also, with vasomotion rhythms influencing neural firing patterns. Another idea that emerges out of the proposed work is that brain's computations may be more comprehensively understood in terms of neuro-glial-vascular dynamics and not in terms of neural firing alone.