Spinal Cord Stimulation in a Mouse Chronic Neuropathic Pain Model

Objective. Development of a spinal cord stimulation (SCS) system in a mouse model of chronic neuropathic pain. Materials and Methods. Male C57BL/6 mice (N = 6) underwent a partial ligation of the sciatic nerve. Development of mechanical hyperalgesia was tested using the withdrawal response to tactile stimuli with the von Frey test. An SCS system was implanted on day 14. On day 16, the mice were stimulated for 30 min (f = 50 Hz; pulse width 0.2 msec and stimulation at 2/3 of motor threshold). Repeated measure analysis of variance (anova ) and paired Student's t‐test with Bonferroni correction were used to evaluate the development of mechanical hyperalgesia and the therapeutic effect of SCS. Results. Five out of six mice developed marked mechanical hyperalgesia in the nerve‐lesioned paw that persisted for the duration of the study (16 days). No changes contralateral to the injury were observed. In four out of five mice, a successful implantation of the electrodes followed by stimulation was achieved. Then, SCS resulted in a fast and robust increase of withdrawal threshold back to pre‐injury levels. After termination of the SCS, the withdrawal threshold of the ipsilateral paw slowly decreased. No effect of SCS on the contralateral paw was noted. Conclusion. The development of a mouse SCS system is described that is practical in use, is reproducible, and shows a comparative therapeutic effect in treatment of chronic neuropathic pain as reported in rat.     

Transverse Tripolar Spinal Cord Stimulation: Results of an International Multicenter Study

Experienced neurosurgeons at eight spinal cord stimulation centers in the United States, Canada, and Europe participated in a study from 1997 to 2000 investigating the safety, performance, and efficacy of a Transverse Tripolar Stimulation (TTS) system invented at the University of Twente, the Netherlands. This device was proposed to improve the ability of spinal cord stimulation to adequately overlap paresthesia to perceived areas of pain. Fifty‐six patients with chronic, intractable neuropathic pain of the trunk and/or limbs more than three months’ duration (average 105 months) were enrolled with follow‐up periods at 4, 12, 26, and 52 weeks. All patients had a new paddle‐type lead implanted with four electrodes, three of them aligned in a row perpendicular to the cord. Fifteen of these patients did not undergo permanent implantation. Of the 41 patients internalized, 20 patients chose conventional programming using an implanted pulse generator to drive four electrodes, while 21 patients chose a tripole stimulation system, which used radiofrequency power and signal transmission and an implanted dual‐channel receiver to drive three electrodes using simultaneous pulses of independently variable amplitude. On average, the visual analog scale scores dropped more for patients with TTS systems (32%) than for conventional polarity systems (16%). Conventional polarity systems were using higher frequencies on average, while usage range was similar. Most impressive was the well‐controlled “steering” of the paresthesias according to the dermatomal topography of the dorsal columns when using the TTS‐balanced pulse driver. The most common complication was lead migration. While the transverse stimulation system produced acceptable outcomes for overall pain relief, an analysis of individual pain patterns suggests that it behaves like spinal cord stimulation in general with the best control of extremity neuropathic pain. This transverse tripole lead and driving system introduced the concept of electrical field steering by selective recruitment of axonal nerve fiber tracts in the dorsal columns.     

Spinal Cord Stimulation in Complex Regional Pain Syndrome Type I of Less Than 12‐Month Duration

Introduction: Complex regional pain syndrome type 1 (CRPS‐1) has a 31% probability of becoming chronic. The early use of spinal cord stimulation (SCS) has been recommended as a strategy to prevent chronicity and functional impairment. Methods: In a prospective study, we treated 74 CRPS‐1 patients with a mean disease duration of 17 weeks with standard therapy consisting of physical therapy, topical dimethyl sulfoxide, analgesics, transcutaneous stimulation, and sympathetic blockade. Patients who did not respond to standard therapy were offered a treatment with SCS. In these patients, we investigated the impact on pain, quality of life, and function. Results: Out of these 74 patients treated with standard therapy, six patients were included for early SCS treatment. The overall mean pain relief after one year was 35%. The mental component of the Short Form 36 improved; however, there was no effect on the physical component. None of the SCS treated patients showed a clear improvement in functional outcome. Discussion: We conclude that the feasibility of performing a randomized controlled trial on early SCS therapy in CRPS‐1 is low because of the good disease improvement with standard therapy in the first year after onset. This study raises questions about the need to use SCS early in the course of CRPS‐1 because of the probable lack of additional benefit compared with SCS in chronic CRPS‐1.     

A Retrospective Comparison of Long-Term Treatment Results of Subcutaneous Stimulation and Spinal Cord Stimulation for Chronic Neuralgia

ObjectivesSpinal cord stimulation (SCS) is known to be an effective long-term treatment option for chronic neuropathic pain. Subcutaneous stimulation (SubQ) is increasingly used to treat chronic back and neck pain, but long-term outcomes are unclear.Materials and MethodsPatients with neurostimulation devices implanted during the past 16 years were evaluated. Their continuation or termination of the treatment was taken as a measure of long-term treatment success. Age, sex, underlying pain condition, stimulation modality (SCS, SubQ, or hybrid), occurrence, and reasons for treatment termination were documented. Patients were classified as long-term responders and long-term nonresponders and analyzed with their clinical data and stimulation modality. The sample consisted of 98 patients. Of these, 66 were treated with SCS, 21 with SubQ, and 11 with a hybrid system.ResultsApproximately 61.3% of patients receiving SubQ terminated the treatment within two years because of ineffectiveness, whereas only 28.8% of patients receiving SCS terminated their stimulation. Back and neck pain were associated with treatment termination (p = 0.011). SubQ was also significantly associated with treatment termination.ConclusionsSubQ seems not to provide substantial long-term pain relief for back and neck pain because most patients abandoned their stimulation therapy.     

A Prospective,Open‐Label,Multicenter Study to Assess the Efficacy of Spinal Cord Stimulation and Identify Patients Who Would Benefit

Objective: To identify patients likely to benefit from spinal cord stimulation (SCS). Materials and Methods: This multicenter, prospective, open‐label study included medical centers experienced in SCS therapy, carried out in 13 physicians in seven centers. We recruited 55 patients with complex regional pain syndrome, failed back surgery syndrome, or peripheral vascular disease. Neurostimulators were implanted in 34 patients found to respond to SCS in a preliminary test, who were then followed for six months. Thirty‐four patients scored their pain on a visual analog scale (VAS) and completed the EuroQol‐5D questionnaire before and after test stimulation and after one and six months. Results: During test stimulation, the mean VAS and quality of life (QOL) scores improved from 74.0 to 23.4 and from 0.430 to 0.664, respectively, in the 34 patients. At six months, the mean VAS score was 29.7 in 29 patients and the mean QOL score was 0.661 in 31 patients. Conclusion: SCS may improve pain management and QOL.     

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain

ObjectivesThe aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain.Materials and MethodsA novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate.ResultsDuring the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: ?60% vs ?46%; legs: ?63% vs ?43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively).DiscussionThe novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary findings.     

Long-Term Outcome of Spinal Cord Stimulation for Chronic Pain Management

Study Design. This is a retrospective study on 102 patients subjected to implantation of a spinal cord stimulation system for nonmalignant chronic pain management. The study was conducted through an extensive questionnaire and telephone interviews by a neutral third party. All the patients were implanted with a complete spinal cord stimulation system without a preliminary trial with a temporarily implanted electrode. Diagnostic categories were neuropathic pain, failed back syndrome, spinal cord Injury pain, and miscellaneous. Average follow-up was 3.8 years (6 months to 8 years). Patients were divided in two groups: all the implanted patients in the survey (Group A) and the implanted patients who experienced some degree of pain relief with the stimulation (Group B). Group B (80 patients) closely matches previously published series where an initial temporary screening was performed. Results. Twenty-one percent of the patients never experienced any pain relief. Of the remaining 80, 75% were still using the stimulator. Fifty-one percent of the 80 patients were experiencing good to excellent results and 20% moderate results. There was no reduction over time in the amount of pain relief in patients who initially had at least 75% pain relief. Patients with initial pain relief between 50% and 74% observed a moderate reduction in their pain relief after two years. Patients who initially experienced less than 50% pain relief observed a dramatic reduction in their results in the long term follow-up. Psychological screening contributed to the success of the procedure. Conclusions. With proper medical and psychological screening and with demonstrated initial pain relief, spinal cord stimulation remains an effective modality in the long-term management of severe chronic pain.     

1.2 kHz High-Frequency Stimulation as a Rescue Therapy in Patients With Chronic Pain Refractory to Conventional Spinal Cord Stimulation

ObjectivesWe aimed to investigate the efficacy of new subperception stimulation paradigms including 1.2 kHz-high-frequency stimulation (HFS) and advanced-HFS field-shaping algorithm (dorsal horn HFS [DHHFS]) in refractory cases which initially benefited from conventional spinal cord stimulation (SCS) and lost the effect throughout time.Materials and MethodsIn the context of a rescue-therapy, patients underwent externalization of the implanted SCS-leads and were tested with multiple combinations of new SCS paradigms. Pain intensity was analyzed using the numeric rating scale (NRS), and data were collected preoperatively and at multiple postoperative follow-ups.ResultsThirty-seven patients underwent externalization of the leads. Mean preoperative NRS-score was 8.1/10 points (SD ± 0.9) for the ON-stimulation period. Patients received a combination of either tonic, burst and 1.2 kHz-HFS, or burst and 1.2 kHz-HFS, DHHFS, or 1.2 kHz-HFS and DHHFS, or 1.2 kHz-HFS alone. The mean postoperative NRS-score after the testing-phase was 3.8/10 points (SD ± 2.5), showing a 48.0% mean reduction (p < 0.001). In total, 29 patients reported a significant reduction above 50% in NRS-scores and therefore were reimplanted with new generators that could deliver the new paradigms. Eight patients underwent full SCS-system explantation. The patients who continued with the new paradigms (n = 29) reported mean NRS-scores of 3.5/10 points (SD ± 1.7) 12 months postoperatively, still showing a significant reduction of 43.3% when compared to preoperative scores (p < 0.001).ConclusionRescue-therapy with combination of multiple waveforms, including tonic, burst, 1.2 kHz-HFS, and DHHFS, was associated with a significant pain relief in patients with failed conventional SCS. This approach is a safe and efficient and should be considered before explantation of the SCS-system.     

Spinal Cord Stimulation in Pregnancy: A Literature Review

Objective: Currently, the use of spinal cord stimulation (SCS) therapy is not recommended in pregnancy because the effects of SCS on the pregnancy and developing fetus are unknown. However, many SCS recipients are women of childbearing age who may later become pregnant. The purpose of the present report is to review and summarize the existing literature on the use of SCS therapy during the prenatal period. Methods: We first present the case of a 38‐year‐old woman from our center who became pregnant after receiving an SCS implantation. We then provide a synopsis of previous reports that were identified in a literature search. We highlight the key findings from these cases as they relate to the course of pregnancy, fetal development, labor and delivery management, fertility, and technical complications. Results: In our literature review, we identified 12 cases of pregnancy in 8 women. To these we add the present case. Conclusions: Women of childbearing age who are candidates for SCS implantation should be tested for pregnancy prior to implantation surgery. They also should be informed about the limited state of our scientific knowledge regarding the impact of this technology on reproductive health. For patients already implanted with SCS, decisions about ongoing use in the event of pregnancy should be made on an individual basis after a careful consideration of potential risks and benefits.