Spinal cord stimulation for complex regional pain syndrome type I: a prospective cohort study with long-term follow-up.

OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment for intractable complex regional pain syndrome type I pain. Long-term data are scarce on effectiveness, degree of pain relief, predictors, and complications. MATERIALS AND METHODS: From 1997 to 2008, 84 consecutive patients who received an implanted SCS system after positive test stimulation were included in the prospective study. Treatment effectiveness was assessed annually as measured by mean visual analog scale pain scores and with the Patients Global Impression of Change scale. Treatment success was defined as at least 30% mean pain relief at end point and treatment failure as explantation of the system. A Cox regression determined if baseline factors were associated with both these outcomes. RESULTS: During 11 years, 41% (95% CI: 27-55) of the patients experience at least 30% pain relief at assessment end point. During 12 years of follow-up 63% (95%CI: 41-85) of the implanted patients still use their SCS device at measured end point. Pain relief of at least 50% one week following test stimulation is associated with a higher probability of long-term treatment success. In 51 patients, 122 reinterventions were performed over 12 years; 13 were due to complications, 44 to battery changes, and 65 reinterventions were equipment related. CONCLUSION: SCS provides an effective long-term pain treatment for 63% (95%CI: 41-85) of implanted patients. Forty-one percent (95%CI: 27-55) of SCS treated patients have at least 30% pain reduction at measurement end point. The number of reinterventions after implantation due to equipment-related problems, battery changes, and complications is 122 over 12 years of follow-up. Sixty-one percent (N = 51) of the patients had at least one reintervention. Mean pain relief of at least 50% (visual analog scale) one week after the test stimulation is associated with long-term treatment success.

Experimental spinal cord stimulation and neuropathic pain: mechanism of action, technical aspects, and effectiveness.

Spinal cord stimulation (SCS) is a valuable treatment for chronic intractable neuropathic pain. Although SCS has gone through a technological revolution over the last four decades, the neurophysiologic and biochemical mechanisms of action have only been partly elucidated. Animal experimental work has provided some evidence for spinal as well as supraspinal mechanisms of neuropathic pain relief of SCS. A SCS computer model of the electrical properties of the human spinal cord revealed many basic neurophysiologic principles that were clinically validated later on. The main question in clinical SCS is how to further improve the effectiveness of SCS as there is still a significant failure rate of 30%. In this context, experimental studies are needed to elucidate which target pain neuron(s) are involved, as well as with what exact electrical stimulation this target neuron can be influenced to produce an optimal supapression of neuropathic pain. This article reviews the basic clinical and experimental technical aspects in relation to the effectiveness of SCS in view of recent understanding of the dorsal horn pain circuit involved. These data may then result in experiments needed for an improved understanding of the mechanisms underlying SCS and consequently lead to improvement and increased effectiveness of SCS in neuropathic pain as a clinical therapy.

Spinal cord stimulation induces c-Fos expression in the dorsal horn in rats with neuropathic pain after partial sciatic nerve injury.

Spinal cord stimulation (SCS) is an established treatment for intractable neuropathic pain, especially CRPS-1. The mechanisms of action of SCS have only been partly elucidated and include suppression of the hyper-excitability of the Wide Dynamic Range neurons and a GABA increase in the dorsal horn. In the present study we demonstrate an increase of c-Fos immunoreactive cells in the dorsal horn after SCS, suggesting early cellular activation that may preclude earlier described electrophysiological and biochemical changes in the dorsal horn after SCS. In a rat model of neuropathic pain, allodynia was induced and quantified using the von Frey test. In 11 rats a SCS device was implanted and spinal cord stimulation performed. Withdrawal threshold were measured every 15 min up to 90 min. A sham group (n=6) also had a SCS device implanted, but did not receive SCS. After SCS the animals were perfused and histology was performed for quantification of c-Fos immunoreactivity in the dorsal horns. We found a significant increase in c-Fos in the SCS group compared to our sham group and control tissue, indicating late cellular activity in the dorsal horn after SCS.

Spinal autofluorescent flavoprotein imaging in a rat model of nerve injury-induced pain and the effect of spinal cord stimulation.

Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level.

Increased efficacy of early spinal cord stimulation in an animal model of neuropathic pain.

Although spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain, pain relief is still not successful in a large group of patients. We suggest that the success of SCS may be related to the timing of SCS during the development of chronic neuropathic pain. We therefore compared the effect of SCS applied after 24h of neuropathic pain (early SCS) and after 16days of neuropathic pain (late SCS). For early SCS, male Sprague-Dawley rats (n=13) were implanted with an SCS device, followed by a partial ligation of the sciatic nerve. Using von Frey monofilaments, tactile allodynia was assessed 24h after ligation. Animals with tactile allodynia received 30min of SCS. Withdrawal thresholds were assessed just before SCS, during SCS and until the return to pre-stimulation withdrawal threshold. Results were compared with the data from late SCS (n=29). Out of the 13 allodynic animals that received early SCS, 10 (77%) responded to SCS with significantly increased withdrawal thresholds, compared to 38% in the late SCS group. The increase of the withdrawal threshold in the early SCS group could still be noticed 90min after termination of SCS. In more than half of these animals, pre-stimulation withdrawal thresholds were reached only the next day. Early SCS resulted in an increased number of responders to SCS and furthermore an increased duration of the effect of SCS as compared to late SCS. Early SCS treatment of neuropathic rats is more effective as compared to the late SCS treatment.

Brush-evoked allodynia predicts outcome of spinal cord stimulation in complex regional pain syndrome type 1.

BACKGROUND: Spinal cord stimulation (SCS) has proven to be an effective however an invasive and relatively expensive treatment of chronic Complex Regional Pain Syndrome type 1(CRPS-1). Furthermore, in one third of CRPS-1 patients, SCS treatment fails to give significant pain relief and 32-38% of treated patients experience complications. The aim of the current study was to develop effective prognostic factors for prediction of successful outcome of SCS. METHODS AND RESULTS: The study population consisted of 36 chronic CRPS patients enrolled in a randomized controlled trial of SCS efficacy. We analyzed various prognostic factors in the group of patients treated with SCS and compared baseline values of possible predictors of outcome in the successfully treated and the not successfully treated group. Success was defined as Patient Global Perceived Impression of Change score of at least "much improved" and pain reduction of at least 2.5 on a visual-analogue scale (VAS score 0-10). Univariate analyses showed that patient age, duration of the disease, localization of the disease, intensity of the pain, and the presence of mechanical hypoesthesia did not predict SCS success. The mean and maximum value of brush-evoked allodynia proved to be statistically significant predictors of outcome. Using Receiver-Operating Characteristic (ROC) curve analyses of maximum allodynia values, the diagnostic sensitivity for successful SCS was 0.75 and the specificity 0.81. CONCLUSION: Brush-evoked allodynia may be a significant negative prognostic factor of SCS treatment outcome after 1 year in chronic CRPS-1.