Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. MATERIALS AND METHODS: This study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. RESULTS: In total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. CONCLUSIONS: Standard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research. ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome: A Possible Target for Immunomodulation?

OBJECTIVE: Complex regional pain syndrome (CRPS) is characterized by continued pain disproportional to the inciting event, sensory abnormalities, vasomotor and sudomotor disturbances, and motor and trophic changes. Inflammatory involvement has been demonstrated in past CRPS studies resulting in pain, swelling, and warmth. Currently, it is unknown whether spinal cord stimulation (SCS) has immunomodulatory properties. The aim of this study was to determine whether SCS has immunomodulatory properties in CRPS patients. METHODS: The primary outcome parameters are cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, IFN-γ), chemokines (IP-10 and Eotaxin), and growth factors (VEGF, PDGFbb, and basic FGF) from interstitial fluid of artificial skin blisters before (T0-baseline without SCS) and after SCS therapy (T1-40 Hz standard frequency stimulation and T2-preferred frequency stimulation). Secondary outcome parameters were baseline demographics, CRPS signs, symptoms, and phenotype (inflammatory, vasomotor, dystonia, or neuropathic). Results were analyzed by means of a MANOVA repeated measures design. RESULTS: After SCS, the expression of both pro- and anti-inflammatory cytokines decreased over time in both the CRPS affected extremity and the contralateral extremity. The levels of IP-10, Eotaxin, VEGF, and PDGFbb were also significantly reduced bilaterally. There were no significant changes in IL-6 and TNF-α before and after SCS. The sensory signs, symptoms, and phenotype improved after SCS. DISCUSSION: SCS in CRPS patients attenuates T-cell activation, improves peripheral tissue oxygenation and decreases anti-angiogenetic activity which results in diminished endothelial dysfunction and improved bloodflow. The possible immunomodulatory effects of SCS opens new therapeutic possibilities in diseases with the involvement of the immune system and vasomotor disturbances, and requires further research on these mechanisms of action.

Burst Spinal Cord Stimulation in a Patient with Complex Regional Pain Syndrome: A 2-year Follow-Up.

UNLABELLED: Spinal cord stimulation (SCS) is an effective therapy to treat most patients with complex regional pain syndrome (CRPS); however, the effect is not always maintained over time. We present a case report of a patient successfully treated with burst SCS after a diminishing effect of conventional tonic stimulation. Burst stimulation is a novel method of SCS consisting of delivering 5 spikes at 500 Hz, 40 times/s (pulse width 1 mseconds). The current output is set to a subthreshold level for paresthesia in the supine position. REPORT OF A CASE: A 65-year-old woman with CRPS in the left upper extremity experienced a diminishing effect of conventional tonic SCS over time, resulting in an increase of pain with a mean Numerical Rating Score (NRS) of 8. After treatment with burst SCS, the NRS declined to 2 and remained at that level for 2 years. An intermediate/brief period, due to increased CRPS activity, resulted in a higher pain score, which was successfully managed by increasing the burst stimulation to a higher level of subthreshold stimulation. DISCUSSION: In this patient with CRPS, burst SCS was successful in reducing pain scores that could no longer be achieved with conventional tonic stimulation. It appears that pain reduction with burst SCS can be sustained for a relatively long period of time.

The effects of mivacurium-induced neuromuscular block on Bispectral Index and Cerebral State Index in children under propofol anesthesia - a prospective randomized clinical trial.

BACKGROUND: In adults anesthetized with propofol, muscle relaxants may decrease the Bispectral Index (BIS). The aim of this prospective randomized trial was to detect the influence of a muscle relaxant bolus on the BIS and the Cerebral State Index (CSI) in children under propofol anesthesia. METHODS: Forty pediatric patients, age 6.6 +/- 3.3 years, weight 24 +/- 9 kg, scheduled for surgical procedures requiring general anesthesia were enrolled. Two minutes after i.v. injection of 0.3 mcg.kg(-1) of sufentanil, general anesthesia was induced by an initial bolus of 3 mg.kg(-1) of propofol, followed by a continuous infusion titrated to achieve a stable BIS value of 50 +/- 5. Patients received either mivacurium 0.25 mg.kg(-1) (Group Miva) or NaCl 0.9% 0.12 ml.kg(-1) (Group Control). Mean BIS and CSI values per minute were compared between (Miva vs. Control) and within groups (Baseline vs 5 min. after study drug administration). RESULTS: The observed changes in BIS and CSI values before and after administration of study drugs revealed no differences between the study groups. Mean baseline BIS and CSI values were lower than 5 min after study drug administration. There were no intergroup differences with respect to BIS and CSI values at any time point. CONCLUSIONS: These data suggest that in pediatric patients anesthetized with propofol, administration of mivacurium has no impact on BIS and CSI values.