RESUMO
Herein, we report the synthesis of aryl derivatives of ketamine and of ketamine's major metabolites hydroxynorketamine (HNK), norketamine (NK), and dehydronorketamine (DHNK) via a microwave-assisted Diels-Alder reaction to form the substituted cyclohexane core structure. Starting with aryl acrylic esters as dienophiles and siloxybutadienes as diene counterparts, a wide range of substituted arylcyclohexylamines was obtained after several modification steps of the initial Diels-Alder products [El Sheikh, S.; Weber, H.; Kortenbrede, L.; Drouvé, N. A broadly applicable Diels-Alder based Synthesis of Ketamine related Arylcyclohexylamines. ChemRxiv 2022, 10.26434/chemrxiv- 2022-xf1l9].
RESUMO
BACKGROUND: Only two out of the five existing randomized studies have reported better results from fusion surgery for chronic low back pain (CLBP) compared to conservative treatment. In these studies the back symptoms of the patients were described simply as "chronic low back pain". One possible reason for the modest results of surgery is the lack of a description of specified symptoms that might be related to a painful segment/disc, and patient selection may therefore be more or less a matter of chance. Previous prospective studies including facet joint injections and discography and eventually MRI have failed to identify patients with a painful segment/disc that will benefit from fusion surgery. PURPOSE: Our purpose was to analyse in detail the pre-operative symptoms and signs presented by patients who showed substantial relief from their back pain following spinal fusion surgery with the aim of possibly finding a pain pattern indicating segmental, discogenic pain. METHODS: We analysed 40 consecutive patients, mean age 41 years, with a history of disabling low back pain for a mean of 7.7 years. Before surgery the patients completed a detailed questionnaire concerning various aspects of their back pain, and findings at clinical examination were thoroughly noted. Monosegmental posterior lumbar interbody fusion without internal fixation was performed using microsurgical technique. Outcome was assessed at 1, 2 and 4 years after surgery and finally at 18 years, using self-reporting measures and assessment by an independent examiner. Assessment at 18 years applied the Balanced Inventory for Spinal Disorders Questionnaire and the Roland-Morris Disability Questionnaire. RESULTS: According to the independent observer's assessment at two years 27 of the 40 patients were much improved. Analysis of the pre-operative depiction of the back symptoms of this group revealed a rather uniform pattern, the most important being: dominating back pain originating in the midline of the spine, with a dull, aching character and stabbing pain in the same area provoked by sudden movements. Most patients in this group also had diffuse pain radiation of various extension down one or both legs and often bladder dysfunction with frequency. At clinical examination, localized interspinal tenderness was observed within the spinal area in question and the patient's back pain was provoked by pressure in that area and by tapping a neighbouring spinous process. At 18 years after surgery 19 patients assessed themselves as much improved. At that time 5 of them had pension due to age, 7 early pension, one worked full time and six patients part time. Eleven patients were re-operated due to defect bony healing. CONCLUSIONS: The results may suggest that the use of a detailed symptom analysis and clinical examination may make it possible to select a subgroup of patients within the CLBP group likely to have better outcome following fusion surgery. IMPLICATIONS: The next step would be to execute prospective studies and if our findings concerning back pain details and signs among CLPB patients can be confirmed this can provide for more accurate selection of patients suitable for fusion surgery.
