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Background: Social support is a multidimensional construct encompassing emotional support as well as pain-focused care and attention, also known as solicitous support. One the one hand, social support is widely believed to positively influence pain symptoms, their intensity, and the ability to cope and influence pain. On the other hand, social support can be negative if it conflicts with the patient's needs or even causes discomfort. How different types of social support influence pain is not very well understood especially because most of the present research originates from laboratory studies, raising uncertainties about its generalizability to the everyday life of individuals with chronic pain., Methods: Here, we tested the effects of emotional, solicitous, and negative social support on pain intensity cross-sectionally in everyday life. We collected data from 20 patients with acute complex regional pain syndrome using a smartphone-based Ecological Momentary Assessment with up to 30 survey prompts over a period of five consecutive days., Results: Our results showed that solicitous social support decreased pain, in particular in male patients. Emotional support was beneficial on pain in women but not in men., Conclusions: Taken together, these findings highlight the differential effects of social support in every-day life on chronic pain., (© 2024. The Author(s).) more...

Background: Long-term opioid use after surgery is a crucial healthcare problem in North America. Data from European hospitals are scarce and differentiation of chronic pain has rarely been considered., Methods: In a mixed surgical cohort of the PAIN OUT registry, opioid use and chronic pain were evaluated before surgery, and 6 and 12 months after surgery (M6/M12). Subgroups with or without opioid medication and pre-existing chronic pain were analysed. M12-chronic pain was categorised as chronic postsurgical pain (CPSP) meeting the ICD-11 definition, chronic pain related to surgery not meeting the ICD-11 definition, and chronic pain unrelated to surgery. Primary endpoint was the rate of M12 opioid users. Variables associated with M12 opioid use and patient-reported outcomes were evaluated., Results: Of 2326 patients, 5.5% were preoperative opioid users; 4.4% and 3.5% took opioids at M6 and M12 (P<0.001). Chronic pain before operation and at M6/M12 was reported by 41.2%, 41.8%, and 34.7% of patients, respectively (P<0.001). The rate of M12 opioid users was highest in group unrelated (22.3%; related 8.3%, CPSP 1.5%; P<0.001). New opioid users were 1.1% (unrelated 7.1%, related 2.3%, CPSP 0.7%; P<0.001). M12 opioid users reported more pain, pain-related physical and affective interference, and needed more opioids than non-users. The predominant variable associated with M12 opioids was preoperative opioid use (estimated odds ratio [95% confidence interval]: 28.3 [14.1-56.7], P<0.001)., Conclusions: Opioid use was low in patients with CPSP, and more problematic in patients with chronic pain unrelated to surgery. A detailed assessment of chronic pain unrelated or related to surgery or CPSP is necessary., Clinical Trial Registration: NCT02083835., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.) more...

Objective: The present study aimed (1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN) and (2) to compare it to the contralateral non-treated side., Design: Retrospective cohort study., Setting: Inselspital, University Hospital Bern, University of Bern., Subjects: Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3-L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008 and 2017 were included., Methods: All patients received a magnetic resonance imaging (MRI) of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed three-dimensionally on standard T2-MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side., Results: A total of 31 treated and 9 non-treated sides (Level L2/3-L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 [0.9 - 2.6] years after RFN (P = .726). We found no differences in the relative fat volume between the treated and non-treated side before (P = .481) and after (P = .578) RFN., Conclusions: Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...

Background: Pain after paediatric appendectomy and tonsillectomy is often undertreated. Benchmarking of hospitals could reveal which measures are associated with improved patient- or parent-reported pain-related outcomes., Methods: A total of 898 anonymised cases from 11 European hospitals participating in PAIN OUT infant were analysed. The children completed a questionnaire on patient-reported outcomes (PROs) 24 h after surgery. According to a composite PRO measure, including pain intensity and pain-related interference, hospitals were allocated to Group I (favourable results), II (average results), and III (unfavourable results). Benchmarking of hospital groups was performed investigating process variables (dosing of non-opioid analgesics, opioids, and dexamethasone) associated with PROs, side-effects, and children's perception of care. Variables associated with PROs were analysed using multinomial regression analysis with the PRO score-related hospital group as a dependent variable (estimated odds ratios [OR], 95% confidence interval [CI])., Results: During the first 24 h after surgery, 1.2 (1.1-1.3) full daily doses of non-opioid analgesics (non-steroidal anti-inflammatory drug [NSAID], paracetamol, metamizole) were administered in group I and 0.7 (0.6-0.8) in group III (P<0.001). Intraoperative dexamethasone was administered to 70.1 and 52.6% of the children in Group I and Group III, respectively (P<0.001). A lower number of full daily doses of non-opioid analgesics: 0.22 [0.15-0.31]), less dexamethasone (0.49 [0.33-0.71]), fewer non-opioid analgesics before the end of surgery (0.37 [0.22-0.62]) and higher opioid doses were associated with hospital allocation to group III vs group I (Nagelkerke's R 2 =0.433)., Conclusions: The results indicated substantial deficits in the concept, application, and dosing of analgesics in paediatric patients after surgery. Timely administration of adequate analgesic doses can easily be introduced into daily clinical practice., Clinical Trial Registration: clinicaltrials.gov NCT02083835., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.) more...

Abstract: Chronic postsurgical pain (CPSP) is defined by pain intensity and pain-related functional interference. This study included measures of function in a composite score of patient-reported outcomes (PROs) to investigate the incidence of CPSP. Registry data were analyzed for PROs 1 day and 12 months postoperatively. Based on pain intensity and pain-related interference with function, patients were allocated to the groups " CPSPF " (at least moderate pain with interference), " mixed " (milder symptoms), and " no CPSPF ". The incidence of CPSPF was compared with CPSP rates referring to published data. Variables associated with the PRO-12 score (composite PROs at 12 months; numeric rating scale 0-10) were analyzed by linear regression analysis. Of 2319 patients, 8.6%, 32.5%, and 58.9% were allocated to the groups CPSPF , mixed , and no CPSPF , respectively. Exclusion of patients whose pain scores did not increase compared with the preoperative status, resulted in a 3.3% incidence. Of the patients without pre-existing pain, 4.1% had CPSPF. Previously published pain cutoffs of numeric rating scale >0, ≥3, or ≥4, used to define CPSP, produced rates of 37.5%, 9.7%, and 5.7%. Pre-existing chronic pain, preoperative opioid medication, and type of surgery were associated with the PRO-12 score (all P < 0.05). Opioid doses and PROs 24 hours postoperatively improved the fit of the regression model. A more comprehensive assessment of pain and interference resulted in lower CPSP rates than previously reported. Although inclusion of CPSP in the ICD-11 is a welcome step, evaluation of pain characteristics would be helpful in differentiation between CPSPF and continuation of pre-existing chronic pain., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.) more...

Background: Attentional deficits in patients with chronic pain are common and well studied. Yet, few studies have examined the effects of chronic pain on more complex cognitive abilities that rely on well-functioning attentional systems. With the current study, we aimed to investigate whether the impact of chronic pain on attention affects creative ideation as measured with an adaptation of the alternate uses task (AUT)., Methods: Performance in the AUT was compared between 33 patients suffering from chronic pain and 33 healthy matched controls. While solving the task, EEG was recorded to measure the degree of internally directed attention assessed by means of task-related power (TRP) changes., Results: The results revealed that patients with chronic pain generated less creative ideas than healthy controls. This lack of performance was accompanied by lower event-related synchronization (ERS), especially in right parietal sites. Furthermore, these ERS differences explained one-third of the inter-group variance in AUT performance., Conclusions: These results suggest that performance decrements in creative ideation in patients with chronic pain may be at least partly attributable to attentional impairments associated with chronic pain., Significance: Chronic pain negatively affects attention and more complex cognitive abilities. However, the underlying psychophysiological mechanisms and the role of attention as a source of these impairments in more complex abilities are poorly understood. By analyzing task-related power changes in the EEG, the role of internal attention in creative ideation could be determined, revealing the functional relationship between chronic pain, attention, and a more complex cognitive ability., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.) more...

Although the interrupting effect of chronic pain on voluntary-directed attention is well-documented, research on the impact of chronic pain on involuntary-directed attention remains incomplete. This study aimed to investigate the influence of chronic pain on involuntary as well as voluntary allocation of attention as, respectively, indexed by the P3a and P3b components in the event-related potential derived from the electroencephalogram. Both involuntary and voluntary captures of attention were compared between 33 patients with chronic pain and 33 healthy controls using an auditory three-stimulus oddball task (with standard, target, and unexpected distractor tones). The results revealed a reduced P3a amplitude as well as a reduced P3b amplitude in patients with chronic pain compared to healthy controls, indicating a detrimental effect of chronic pain on involuntary and voluntary attention, respectively. This study extends the picture of the impairing effects of chronic pain on attentional allocation to a current task and attentional allocation to information outside the focus of attention. (PsycInfo Database Record (c) 2022 APA, all rights reserved). more...

Neuropathic pain: Pharmacotherapy Abstract. The identification and treatment of neuropathic pain (NP) still represents a major challenge to an interdisciplinary team. Specific pharmacotherapy is an important pillar of a multimodal therapy strategy that should finally follow a biopsychosocial approach. Unfortunately, classic WHO-Step-I analgesics fail to treat NP. According to current evidence, a permanent therapy with opioids (WHO-Step-II and -III) exposes patients to long-term risks that can hardly justify the midterm success of these substances. Therefore, knowledge of the dosage, use and side effects of the first-line drugs such as tricyclic antidepressants (TCA), serotonin-norepinephrine reuptake inhibitors (SNRI) and gabapentinoids is essential. Treatment should follow the "start low, go slow" concept, while a good patient education is crucial. Topical therapy with Lidocaine and Ambroxol actively includes the patient in the therapy regimen. High-dose therapy with capsaicin patches (8 %) remains in the hands of pain specialists. Perioperative prevention of neuropathic pain with systemic medication failed to prove efficacy by now. However, the perineural application of local anaesthetics using nerve blocks in thoracic and breast surgery as well as in caesarean section showed potential to prevent chronic, postoperative pain (CPOP). In the case of systemic diseases causing neuropathies, such as diabetes mellitus, active herpes zoster, multiple sclerosis, malnutrition, the optimization of a causal drug therapy stays eminently important. more...

Four children were operated on by the transpubic approach for injury to the vagina or urethra and to correct malformations within the pelvis minor. One boy had posttraumatic stricture of the urethra, and a girl presented with disruption of the urethra and vagina. One of two boys who had congenital malformations was treated for epispadias and incontinence; the other for a large urethral diverticulum caused by anal atresia. Total reconstruction was achieved, and no complications of symphysis restoration were observed. more...

A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18-hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor. more...

18,19-Dihydroxycorticosterone (18,19(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B) measurements were carried out on the urine of patients with primary aldosteronism (PA), essential hypertension (EHT), and liver cirrhosis with (LC, SA (+)) and without (LC, SA (-)) aldosteronism. The separation of these steroids was performed by extraction and high-performance liquid chromatography followed by radioimmunoassay (RIA) with specific antibodies prepared in our laboratory. 18,19(OH)2-B excretion was elevated in patients with PA (24 +/- 5.9 [+/- SE] micrograms/24 hr; n = 15) and LC, SA (+) (83 +/- 9.4 micrograms/24 hr; n = 8). Values in LC, SA (-) (3.1 +/- 1.2 micrograms/24 hr; n = 8) and in EHT (3.7 +/- 0.4 micrograms/24 hr; n = 42) were found to be similar to those in normal subjects (5.5 +/- 0.9 micrograms/24 hr; n = 30). The values of urinary 18-OH-19-nor-B in PA and LC, SA (+) were higher than in LC, SA (-) EHT and normal subjects (P less than 0.05). Values in the latter three groups, as compared with each other, did not show significant alterations. Nothing is known about the biologic relevance of 18,19(OH)2-B and very little about that of 18-OH-19-nor-B, but the latter steroid seems to potentiate experimental renal hypertension. One can speculate about possible roles of both steroids as precursors of other steroids, e.g., the biologically potent mineralocorticoid 19-noraldosterone. The data obtained suggest that it is not relevant to measure the urinary levels of either steroid in these clinical syndromes. more...

Two enzyme-linked immunosorbent assays were established and compared for the estimation of plasma aldosterone. In the first method immobilized aldosterone-protein complexes on the ELISA plates compete with aldosterone to be determined for the binding of certain amount of anti-aldosterone antibodies. The sensitivity of this method depends on the protein carrier used to conjugate with aldosterone. In the second method, anti-aldosterone antibodies adsorbed on ELISA plates compete for binding of known amount of the enzyme-labeled aldosterone and aldosterone to be determined. The highly specific rabbit anti-aldosterone antibodies were obtained by injection of aldosterone-oxime thyroglobulin. The detection limit of aldosterone in both methods ranged between 2-20 pg. The proposed assays are suitable for the determination of aldosterone in biological fluids compared with other reported ELISA assays, as well as with RIA. more...

Infusion of Ring-A-reduced metabolites of aldosterone in adrenalectomized male rats for 4 days revealed that 5 alpha-Ring-A-reduced derivatives, 5 alpha-dihydroaldosterone (5 alpha-DHAldo; 2.5-5.0 micrograms/day), 3 alpha,5 alpha-tetrahydroaldosterone (3 alpha,5 alpha-THAldo; 5-25 micrograms/day), and 3 beta,5 alpha-THAldo (50-175 micrograms/day) possessed intrinsic Na+-retaining activity. The same infusions of 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo, and 3 beta,5 alpha-THAldo, also lowered the urinary excretion of potassium. The 5 beta-Ring-A-reduced derivative 3 alpha,5 beta-THAldo did not demonstrate either of these biological properties. In another set of experiments, on the fourth day of infusion, aldosterone (0.1 microgram/rat) was administered acutely subcutaneously; none of the Ring-A-reduced derivatives altered the Na+-retaining activity of aldosterone. However, in a dose-dependent manner, both 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo blunted the urinary K+-secretory effect of aldosterone; low dosages of 5 alpha-DHAldo and larger dosages of 3 alpha,5 beta-THAldo did not. Thus, the 5 alpha-reduced derivatives of aldosterone not only lowered urinary Na+ and K+ excretion in their own right, but two of them blunted the kaliuretic response of the parent mineralocorticoid, aldosterone. Further experiments will be required to determine whether these aldosterone metabolites are further metabolized or interconverted during the expression of the regulatory properties described here and whether these properties are physiologically relevant. more...

The microbial enzymatic reduction of 1,4-androstadiene-3,17-dione (ADD) to 4-androstene-3,17-dione (AD), testosterone and 1-dehydrotestosterone (DHT) is described. Two reducing activities observed in washed cell suspensions and cell free extracts of Mycobacterium sp. NRRL B-3805 were found to account for these bioconversions. One was a 1-ene-steroid reductase and the other a 17-keto steroid reductase. The first reducing activity was found to appear in the soluble cell fraction whereas the latter could be precipitated by centrifugation. Maximum 1-ene-steroid reductase specific activity was achieved during the exponential growth phase of the organism and significantly increased upon induction with ADD. The 1-ene-steroid reductase was partially purified (30-fold) by ammonium sulfate fractionation, gel-filtration and ion-exchange chromatography, and was eluted from a Sephacryl S-300 column with an Mr = 115,000. The 1-ene-steroid reductase activity was NADPH-dependent and had specificity towards steroid compounds containing C-1,2 double bond with an apparent Km for ADD of 2.2 X 10(-5) M. The reverse reaction catalyzing C-1,2 dehydrogenation could not be detected in our preparations. The results suggest that in Mycobacterium sp NRRL B-3805 and B-3683 the steroid C-1,2 dehydrogenation and 1-ene reduction are two separable activities. more...

The compounds named in the title have been synthesized from the di-(ethylene ketal) of 21-hydroxy-3,20-dioxo-19-norpregn-5-ene-18, 11 beta-lactone and its 5(10)-ene isomer. Reduction of this mixture 1 with sodium aluminum bis-(methoxyethoxy)hydride furnished the 11 beta, 18, 21-triol 2a. Conversion to the 18,21-diacetate 2b, followed by deketalization to the free dione 3 and hydrolysis, afforded 18-hydroxy-19-norcorticosterone 4a which, in the solid state and probably in solution, has the 18,20-hemiacetal structure. Periodate oxidation of 4a gave 11 beta-hydroxy-3-oxo-19-norandrost-4-ene-17 beta, 18-carbolactone 5a, and acid treatment of 4a or its precursor 2a yielded 18-deoxy-19-noraldosterone 6a. The structure of 5a was confirmed by mass spectrometry and 1H nmr, and compared with that of its C-19 methyl homolog 5b and 19-noraldosterone-gamma-etiolactone 8. In particular, 2-D nmr COSY 45 experiments, affording full 1H line assignments, have rigorously established the "natural" beta (axial) configuration of the C-10 hydrogen in the 19-nor lactones 5a and 8, and therefore also in the related 4a, 6a and 19-noraldosterone 7. more...

The 3 beta, 5 alpha-, 3 alpha, 5 alpha- and 3 alpha, 5 beta-tetrahydro derivatives 19, 20 and 27 of 19-noraldosterone (1) were prepared to facilitate the search for these compounds in urine. The diketal 4, consisting of a 2:1 mixture of the 5,6- and 5(10)-ene isomers, was hydrogenated with Pd-C and partially hydrolyzed to 5 alpha, 10 alpha- and 5 alpha, 10 beta-dihydroketals 8 and 10 in a 1:2.5 ratio. Assignment of protons was done with aid of COSY 45 experiments. Compound 10 was reduced with diisobutylaluminum hydride (DIBAH) to 4 products: the 3 alpha- and 3 beta-ol hemiacetals 16 and 15, and the corresponding tetraols 14 and 13. Alternatively, hydrogenation of the 4-en-3-one 2 gave 10, its 5 beta, 10 beta-isomer 21 and the tetrahydro compound 22, in a 4:2:1 ratio. A better way to prepare the 5 beta, 10 beta-series involved microbial conversion of 2 with Clostridium paraputrificum, and the resulting tetrahydrolactone 23 was reduced with DIBAH to the hemiacetal 24. Acid hydrolysis of 16, 15 and 24 afforded 20, 19 and 27, respectively. According to [1H]-NMR, in solution 20 and 24 exist as mixtures of isomers, while 19 appears in one form only. Periodate oxidation converted 19 and 27 into their gamma-etiolactones 18 and 28. EI MS base peaks are different and characteristic for 19, 20 and 27. more...

The mineralocorticoid (MC) activities of 19-hydroxyaldosterone (19-OH-Aldo) and 19-nor-aldosterone (19-nor-Aldo) were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall MC activity is expressed as the ability to decrease the urinary Na+ to K+ ratio; antinatriuretic activity is represented by decreases in the urinary Na+ to creatinine ratio, and kaliuretic activity by increases in the K+ to creatinine ratio. All measurements were made on urine collected 1-3 h postinjection. In this assay, 19-OH-Aldo was 1/100th to 1/140th as active as Aldo, and 19-nor-Aldo possessed MC activity similar to that of Aldo; both steroids possessed antinatriuretic and kaliuretic activities. In contrast, when assayed in vitro in the isolated toad urinary bladder, the natriferic responses of both 19-OH-Aldo and 19-nor-Aldo (10(-8), 10(-7), and 10(-6) M) were not significantly different from those caused by equivalent concentrations of Aldo. 3 beta-Hydroxy-delta 5-Aldo is active as a MC in the adrenalectomized male rat, being 1/20th to 1/35th as active as Aldo, but, in contrast to 19-OH-Aldo, was less active in the isolated toad bladder system. 19-OH-Aldo, 19-nor-Aldo, and 3 beta-hydroxy-delta 5-Aldo could represent important new classes of Aldo analogs. more...

The relative hypertensinogenic potencies of recently synthesized 19-nor-aldosterone and its precursor 19-OH-aldosterone were assessed in comparison to that of aldosterone (Aldo) in young (6-week-old) adrenalectomized (ADX) spontaneously hypertensive rats (SHR). Infusion of 19-nor-aldosterone for 2 weeks by Alza mini-osmotic pumps caused significant, dose-dependent increases in the systolic blood pressure (BP) of young ADX SHR; dosages of 0.1 and 0.5 microgram/day raised the BP from 127 +/- 2 mmHg to 164 +/- 9 and 180 +/- 11 mmHg, respectively. During this period, control ADX SHR receiving vehicle only remained normotensive. Similar increases in BP were seen only with infusion of slightly higher dosages of Aldo (0.5 and 1.0 micrograms/day). In contrast, 19-OH-aldosterone infused at higher dosages (10 or 25 micrograms/day) caused little change in BP of ADX SHR. Full suppression of plasma renin activity (PRA) was observed with 0.1 and 0.5 microgram/day 19-nor-aldosterone, whereas Aldo caused similar decreases in PRA only at dosages of 0.5 microgram/day and higher. Interestingly, although infusions of 19-OH-aldosterone did not cause a significant change in BP, these dosages (10 and 25 micrograms/day) significantly suppressed PRA. These studies which show that 19-nor-aldosterone is equipotent to Aldo, and perhaps slightly more active in ADX SHR, indicate that 19-nor-aldosterone is a potentially important hypertensinogenic steroid. more...

Urines of patients with primary aldosteronism were extracted, the extract repeatedly chromatographed with reversed phase HPLC. The fractions immunoactive against 18-hydroxycorticosterone antiserum and being more polar than the 18-hydroxycorticosterone were further purified, derivatized and investigated by GC/MS. In this manner the natural occurrence of the 18, 19-dihydroxycorticosterone, which was lately synthetized, in human urine was confirmed. more...