Cryoneurolysis' outcome on pain experience (COPE) in patients with low-back pain: study protocol for a single-blinded randomized controlled trial.

BACKGROUND: Low-back pain, including facet joint pain, accounts for up to 20 % of all sick leaves in DenmarkA proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome. METHODS: A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity ≥ 50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is the patients' impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are a reduction in low-back pain intensity (numeric rating scale) and quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory). Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months (T6). DISCUSSION: This study will provide information on the effectiveness of cryoneurolysis vs. the effectiveness of radiofrequency ablation or placebo for patients with facet joint pain, and help to establish whether cryoneurolysis should be implemented in clinical practice for this patient population. TRIAL REGISTRATION: The trial is approved by the ethical committee of Central Jutland Denmark with registration number 1-10-72-27-19 and the Danish Data Protection Agency with registration number 666,852. The study is registered at Clinicaltrial.gov with the ID number NCT04786145 .

Pelvic floor electrophysiology in spinal cord injury.

OBJECTIVE: The study aimed to investigate sacral peripheral nerve function and continuity of pudendal nerve in patients with chronic spinal cord injury (SCI) using pelvic floor electrophysiological tests. METHODS: Twelve patients with low cervical or thoracic SCI were prospectively included. Quantitative external anal sphincter (EAS) muscle electromyography (EMG), pudendal nerve terminal motor latency (PNTML) testing, bulbocavernosus reflex (BCR) testing and pudendal short-latency somatosensory-evoked potential (SEP) measurement were performed. RESULTS: In EAS muscle EMG, two patients had abnormal increased spontaneous activity and seven prolonged motor unit potential duration. PNTML was normal in 10 patients. BCR was present with normal latency in 11 patients and with prolonged latency in one. The second component of BCR could be recorded in four patients. SEPs showed absent cortical responses in 11 patients and normal latency in one. CONCLUSIONS: Pudendal nerve and sacral lower motor neuron involvement are significantly associated with chronic SCI, most prominently in EAS muscle EMG. The frequent finding of normal PNTML latencies supports earlier concerns on the utility of this test; however, BCR and pudendal SEPs may have clinical relevance. SIGNIFICANCE: As intact peripheral nerves including pudendal nerve are essential for efficient supportive therapies, pelvic floor electrophysiological testing prior to these interventions is highly recommended.

The artificial somato-autonomic reflex arch does not improve bowel function in subjects with spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Although introduced for neurogenic bladder dysfunction, it has been suggested that the artificial somato-autonomic reflex arch alleviates neurogenic bowel dysfunction (NBD). We aimed at evaluating the effects of the reflex arch on NBD. SETTING: Denmark. METHODS: Ten subjects with supraconal spinal cord injury (SCI) (nine males, median age 46 years) had an anastomosis created between the ventral part of the fifth lumbar or first sacral nerve root and the ventral part of the second sacral nerve root. Standardized assessment of segmental colorectal transit times with radiopaque markers, evaluation of scintigraphic assessed colorectal emptying upon defecation, scintigraphic assessment of colorectal transport during stimulation of the reflex arch, standard anorectal physiology tests and colorectal symptoms were performed at baseline and 18 months after surgery. RESULTS: No significant change was observed in colorectal emptying upon defecation (median 31% of the rectosigmoid at baseline vs 75% at follow-up, P=0.50), no movement of colorectal contents was observed during stimulation of the reflex arch. Segmental colorectal transit times, anal sphincter pressures and rectal capacity did not change, and no change was seen in NBD score (median 13.5 (baseline) vs 12.5 (follow-up), P=0.51), St Marks fecal incontinence score (4.5 vs 5.0, P=0.36) and Cleveland constipation score (6.0 vs 8.0, P=0.75). CONCLUSIONS: The artificial somato-autonomic reflex arch has no effect on bowel function in subjects with supraconal SCI.

Sacral anterior root stimulation improves bowel function in subjects with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the long-term effect of the sacral anterior root stimulator (SARS) on neurogenic bowel dysfunction in a large, well defined spinal cord injury (SCI) cohort. SETTING: Department of Neuro-Urology, Bad Wildungen, Germany. METHODS: Subjects undergone surgery at for SARS-SDAF (sacral deafferentation) between September 1986 and July 2011 (n=587) answered a questionnaire. In total, 277 SARS subjects were available for the baseline (recall) and follow-up comparison. RESULTS: Median age was 49 years (range: 19-80), time from SCI to surgery was 10 years (range: 0-49) and from surgery to follow-up 13 (range: 1-25). Of the responders 73% used SARS for bowel emptying. On visual analog scale (VAS) ranging from 0-10 (best), satisfaction with SARS was 10. Baseline and follow-up comparison showed a decline in the median VAS score 0-10 (worst) for bowel symptoms from 6 (range: 4-8) to 4 (range: 2-6), P<0.0001; median neurogenic bowel dysfunction score from 17 (range: 11-2) to 11 (range: 9-15), P<0.0001; median St Marks score from 4 (range: 0-7) to 4 (range: 0-5), P=0.01; and median Cleveland constipation score from 7 (range: 6-10) to 6 (range: 4-8), P<0.0001. Use of suppositories, digital evacuation and mini enema and subjects totally dependent on assistance during defecation were significantly lower after SARS. CONCLUSIONS: The SARS has the potential to be one of the few treatment methods targeting multiple organ dysfunctions following SCI.

Colorectal transport during defecation in subjects with supraconal spinal cord injury.

STUDY DESIGN: Clinical study. OBJECTIVES: To explore how supraconal spinal cord injury (SCI) affects colorectal emptying at defecation. Further, to relate findings to subject symptomatology expressed by bowel function scores and gastrointestinal transit time (GITT). SETTING: Aarhus University Hospital, Denmark. METHODS: Colorectal contents were marked by oral intake of (111)In-coated resin pellets. Movement of stools at defecation was assessed by comparing scintigrams performed before and just after defecation. Results from 15 subjects with SCI (14 males, median age=47 years (range: 22-74 years), SCI level: C5-Th9) were compared with those from 16 healthy volunteers (12 males, median age=31 years (range: 24-42 years)). Bowel symptoms were described from standard symptom scores, and GITT was assessed by radiopaque markers. RESULTS: Median emptying at defecation was 31% of the rectosigmoid (range: 0% to complete emptying of the rectosigmoid and 49% of the descending colon) in subjects with SCI and 89% of the rectosigmoid (range: 53% to complete emptying of the rectosigmoid and the descending colon, and 3% of the transverse colon) in the control group (P<0.01). Colorectal emptying at defecation was associated with the St Mark's fecal incontinence score (P=0.02) but not with the Cleveland constipation score (P=0.17), the neurogenic bowel dysfunction score (P=0.12) or GITT (P=0.99). CONCLUSION: Supraconal SCI results in significantly reduced emptying of stools at defecation. This is independent of changes in GITT.

Amino acid sequence around the active-site serine residue in the acyltransferase domain of goat mammary fatty acid synthetase.

Goat mammary fatty acid synthetase was labelled in the acyltransferase domain by formation of O-ester intermediates by incubation with [1-14C]acetyl-CoA and [2-14C]malonyl-CoA. Tryptic-digest and CNBr-cleavage peptides were isolated and purified by high-performance reverse-phase and ion-exchange liquid chromatography. The sequences of the malonyl- and acetyl-labelled peptides were shown to be identical. The results confirm the hypothesis that both acetyl and malonyl groups are transferred to the mammalian fatty acid synthetase complex by the same transferase. The sequence is compared with those of other fatty acid synthetase transferases.

The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs.

Irreversible ischemic myocardial cell injury developes in an increasing number of cells as the duration of coronary occlusion is prolonged. The present study quantitates myocardial necrosis produced by 40 minutes, 3 hours, or 6 hours of temporary circumflex coronary occlusion (CO) followed by 2 to 4 days of reperfusion, or by 24 or 96 hours of permanent circumflex ligation in pentobarbital anesthetized open chest dogs. After 40 minutes of ischemia, myocyte necrosis was subendocardial but with increasing duration of coronary occlusion, irreversible injury progressed as a wavefront toward the subepicardium. Transmural necrosis was 38 +/- 4% after 40 min, 57 +/- 7% after 3 hours, 71 +/- 7% after 6 hours and 85 +/- 2% after 24 hours of ischemic injury. These results document the presence of a subepicardial zone of ischemic but viable myocardium which is available for pharmacologic or surgical salvage for at least three and perhaps six hours following circumflex occlusion in the dog.

Infarct size reduction by propranolol before and after coronary ligation in dogs.

Coronary occlusion in the dog results in irreversible myocardial cell injury which develops first in subendocardial areas of severe ischemica and subsequently spreads into mid and subepicardial areas of moderate ischemia. The effect of propranolol on this progression of ischemic injury was evaluated. Three groups of dogs were studied: 1) untreated, 2) treated with propranolol before and throughout coronary ligation, and 3) treated with propranolol beginning three hours after ligation. Dogs were sacrificed 24 hours after coronary ligation and necrosis was quantitated from histologic sections of transmural slices through the posterior papillary muscle. Propranolol reduced infarct size by preventing necrosis in peripheral (subepicardial) areas of moderately ischemic myocardium. Pretreatment with propranolol reduced necrosis from 85 +/- 3% (untreated) to 52 +/- 4% (P less than 0.05). Delayed propranolol therapy was about half as effective as pre-treatment and reduced necrosis to 71 +/- 3% (P less than 0.05). Propranolol also limited microvascular injury so that perfusion defects, detected with the dye thioflavin S, were smaller in treated dogs.

On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs.

Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d, l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d, l-propranolol. A dose of 0.005 mg/kg d, l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d, l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d, l-propranolol (a level at which direct "membrane stabilizing" effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.