One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain

Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P < 0.001) and resulted in higher scores of the State Anxiety Inventory (P < 0.01). In addition to previously reported hyperalgesia to heat (P < 0.05) and blunt pressure (P < 0.05), study participants developed hyperalgesia to cold (P < 0.01) and increased mechanical pain sensitivity to pinprick stimuli (P < 0.05) but no changes in temporal summation. Paradoxical heat sensations or dynamic mechanical allodynia were absent. TSD selectively modulated nociception, since detection thresholds of non-nociceptive modalities remained unchanged. Our findings show that a single night of TSD is able to induce generalized hyperalgesia and to increase State Anxiety scores. In the future, TSD may serve as a translational pain model to elucidate the pathomechanisms underlying the hyperalgesic effect of sleep disturbances.     

Lombalgie chronique et réentraînement à l’effort : application de la notion de niveau de douleur cliniquement acceptable

Objectives

To search for predictors of reduced low back pain under the patient acceptable symptom state (PASS) at the end of a functional restoration program (FRP) in chronic low back pain, and then to compare the effectiveness of FRP depending on the rate of people returning to work, the acceptability threshold of pain has been reached or not at the end of the program.

Method

Open prospective study on 303 patients with chronic low back pain included in a FRP. An assessment of the deficiencies (finger-tip-to-floor (cm) and Schöber tests (cm), VO2 max (l/min), Shirado and Sorensen tests (seconds), lumbar and radicular VAS (0-100), the functional disability (Wadell and Quebec scales (0-9 and 0-100), and the psychological status (Beck and Hamilton scale (0-35 and 0-30), HAD scale (0-21), FABQ (0-42 and 0-24)) was conducted at the beginning and end of the program. Data on the work were also collected (arduous physical labor, work-related accident or not, sick leaves or not and length, return to work at the end of the program). The variables associated with a PASS at the end of the FRP and a correlation between the level of pain and the return to work were sought.

Results

The parameters were significantly improved : finger-tip-to-floor test (−17,5 ± 16,2), Schöber test (−0,5 ± 5,4), lumbar VAS(−6,3 ± 23,6), VO2 max (0,14 ± 0,4), Wadell (−1,3 ± 2,4), Quebec (−10,5 ± 17), Beck D (−3,1 ± 4,5), Beck A (−2,5 ± 4,3), HAD D (−2,4 ± 4,7), HAD A (−1,3 ± 3,8) et FABQ1 (−5,7 ± 11,6), FABQ2 (−3,9 ± 9,6) scores, endurance of the flexor (35 ± 63,83) and extensor (44,8 ± 112) spine. Patients reaching the PASS for pain level return significantly more to work (73% versus 52%). Five parameters indicative of a reduction of back pain under the PASS were identified : lumbar VAS and endurance of the flexor spine at the beginning, changes in finger-tip-to-floor test, radicular VAS and Beck score for anxiety.

Conclusion

The PASS appears to be a relevant concept associated with a successful return to work for patients with chronic low back pain and severe disability after a program of FRP.     

Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents

Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n = 39 chronic pain; n = 58 healthy) aged 12-18, 70.1% female participated. Adolescents completed pain diary ratings (0-10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p < .001) and minutes awake after sleep onset (WASO) (p < .05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next-day pain than healthy participants (p = .05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.     

Altered experimental pain perception after cerebellar infarction

Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. In the present study, we used experimental pain testing to compare acute pain perception and endogenous pain inhibition in 30 patients 1 to 11 years after cerebellar infarction and in 30 sex- and age-matched healthy control subjects. Compared to controls, patients exhibited a significantly increased pain perception in response to acute heat stimuli (44°C–48°C, average pain intensity rating for patients 3.4 ± 2.8 and for controls 1.5 ± 1.7 [on a numeric rating scale of 0–10], P < .01) and to repeated 256 mN pinprick stimuli (1.3 ± 1.9 vs 0.6 ± 1.0 [0–10], P < .05). Heat hyperalgesia in patients was more pronounced on the body side ipsilateral to the infarction. In addition, patients showed reduced offset analgesia (change in pain intensity rating: 0.0% ± 15.8% vs −16.9% ± 36.3%, P < .05) and reduced placebo analgesia (change in pain intensity rating: −1.0 ± 1.1 vs −1.8 ± 1.3 [0–10], P < .05) compared to controls. In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation.     

Differential processing of laser stimuli by Aδ and C fibres in major depression

Clinical studies have revealed that up to 92% of major depressed patients report pain complaints such as back or abdominal pain. Furthermore, patients suffering from depression exhibit increased superficial pain thresholds and decreased ischemic (deep) pain thresholds during experimental pain testing in comparison to healthy controls. Here, we aimed to investigate a putative role of Aδ- and C-fibre activation in altered pain perception in the disease. Laser-evoked potentials (LEPs) of 27 unmedicated depressed patients and 27 matched controls were recorded. Aδ and C fibres were activated separately. Amplitudes and latencies of N2 and P2 peaks of Aδ- (Aδ-LEP) and C-fibre- (C-LEP) related LEPs were evaluated. Depressed patients showed significantly decreased Aδ-LEP amplitudes (N2 peak: P = 0.019; P2 peak: P = 0.024) and delayed C-LEP latencies (P2 peak: P = 0.0495; N2 peak: P = 0.0556). In contrast, C-LEP amplitudes and Aδ-LEP latencies were unaffected. Our results might be suggestive of the differential impact of physiological changes on pain processing in depression. Thus, Aδ-LEP might reflect the physiological correlate of the augmented superficial pain thresholds during depression. On the contrary, the C-fibre component mediates the facets of pain processing, outlasting the stimulation period, and has been shown to be exaggerated in chronic pain states. Therefore, the functional over-representation of the C-fibre component found in our study might be a possible link between depression and associated pain complaints.     

Mechanisms of pain in distal symmetric polyneuropathy: A combined clinical and neurophysiological study

In patients with distal symmetric polyneuropathy we assessed non-nociceptive Aβ- and nociceptive Aδ-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Aβ-fibre function, and laser-evoked potentials (LEPs) to assess Aδ-fibre function. Patients with pain had the same age (P > 0.50), but a longer delay since symptom onset than those without (P < 0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.0001), NCS data did not differ between groups (P > 0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P < 0.0001). Our findings indicate that the impairment of Aβ-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds.     

Assessing the quality of sleep in Greek primary caregivers of patients with secondary progressive multiple sclerosis: a cross-sectional study

Context

Several studies have investigated the prevalence of sleep disorders in patients suffering from multiple sclerosis (MS) and have shown that up to 54% of patients may have significantly more sleep problems than the general population. To our knowledge, however, no data are available about the quality of sleep of the primary caregivers of patients with MS.

Objectives

The objectives of the current cross-sectional study were to assess the quality of sleep in Greek primary caregivers of patients with MS and to investigate its relationship with the degree of caregivers' emotional distress.

Methods

Twenty-two male and 13 female primary caregivers (mean age 47.3 ± 12.4 years) of an equal number of patients with MS, who consented to participate, completed the validated Greek version of the Pittsburgh Sleep Quality Index (PSQI) and the validated Greek version of the Hospital Anxiety and Depression Scale (HADS). Thirty-five age-, gender-, and education-matched healthy controls were used for comparisons.

Results

Caregivers experienced a higher degree of anxiety than depression. The mean score in the seven-item HADS-A subscale was 9.5 ± 4 (range 3-15) and the mean score in the seven-item HADS-D subscale was 7.1 ± 3.1 (range 2-14). The mean scores of caregivers on both HADS-A and HADS-D were significantly higher than those of controls (P < 0.001). The PSQI scoring demonstrated that 19 (54.3%) caregivers had poor sleep quality (cut-off value of >5). The mean values of caregivers for the PSQI were 6.0 ± 2.8 (range 2-12) compared with controls, who scored at a significantly lower level (1.5 ± 0.8; P < 0.001). Poor quality of sleep was significantly correlated with increased levels of anxiety (r = 0.392; P = 0.02) and depression (r = 0.424; P = 0.01). Among the PSQI components, the sleep duration and sleep latency were mostly influenced by the degree of emotional distress.

Conclusion

A significant proportion of primary caregivers of MS patients experience poor sleep quality. The degree of their emotional distress appears to significantly influence their quality of sleep. Appropriate psychopharmacological interventions may be required for those individuals.     

Effect of lingual nerve block on burning mouth syndrome (stomatodynia): A randomized crossover trial

Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature the main location of which, peripheral or central, remains unknown. A randomised, double-blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam, the patient’s response to a psychological questionnaire, and the taste and heat thresholds. The spontaneous burning was measured with a visual analogue scale (VAS) just before and 15 min after injection. The decreases in VAS score after lidocaine or saline injection were not significantly different (2.7 ± 3.9 and 2.0 ± 2.6, respectively; n = 20). However, two groups of patients could be identified: in a “peripheral group” (n = 10) the VAS decrease due to lingual nerve injection was 4.3 ± 3.1 cm after lidocaine and 0.9 ± 0.3 cm after saline (p = 0.02). In a “central group” (n = 7), there were an increase in pain intensity score (−0.8 ± 2.6 cm) after lidocaine and a decrease (1.5 ± 3.0 cm) after saline (p = 0.15). An increase in the hospital anxiety and depression (HAD) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age-and-sex-matched controls (p < 0.05). Topical clonazepam treatment tended to be more effective (p = 0.07) and HAD score lower (p < 0.03) in the peripheral than in the central group. These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral, central or mixed depending on the individual. Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating.     

Attentional bias to pain-related information: A meta-analysis

This meta-analysis investigated whether attentional bias, that is, the preferential allocation of attention to information that is related to pain, is a ubiquitous phenomenon. We also investigated whether attentional bias effects are related to the methodological quality of the study, to procedural differences in their measurement, or to individual differences in pain severity, pain-related fear, anxiety, and depression. Results indicated that individuals who experience chronic pain (n = 1023) display an attentional bias towards pain-related words or pictures, but this bias was of a small effect size (d = 0.134), and did not differ from that in control groups (d = 0.082; n = 1398). No evidence was found for an attentional bias towards pain-related words and pictures for acute pain (d = 0.049), procedural pain (d = 0.142), and experimental pain (d = 0.069). However, research in which attentional bias towards signals of impending experimental pain in healthy volunteers was investigated, revealed an attentional bias of medium effect size (d = 0.676). Moderator analyses in the chronic pain group identified important procedural variables that affected the presence and magnitude of an attentional bias towards pain-related words and pictures, that is, type and exposure time of pain-related information. None of the individual difference variables affected the magnitude of the attentional bias. Implications of current findings and future directions are discussed.     

Effect of a warm footbath before bedtime on body temperature and sleep in older adults with good and poor sleep: An experimental crossover trial

Background

The decrease in core body temperature before sleep onset and during sleep is associated with dilation of peripheral blood vessels, which permits heat dissipation from the body core to the periphery. A lower core temperature coupled with a higher distal (hands and feet) temperature before sleep are associated with shorter sleep latency and better sleep quality. A warm foot bath is thought to facilitate heat dissipation to improve sleep outcomes.

Objectives

This study examined the effect of a warm footbath (40 °C water temperature, 20-min duration) on body temperature and sleep in older adults (≥55 years) with good and poor sleep.

Design

Two groups and an experimental crossover design was used.

Setting and participants

Forty-three adults responded to our flyer and 25 participants aged 59.8 ± 3.7 years (poor sleeper with a Pittsburgh Sleep Quality Index score ≥ 5 = 17; good sleepers with a Pittsburgh Sleep Quality Index score < 5 = 8) completed this study.

Methods

All participants had body temperatures (core, abdomen, and foot) and polysomnography recorded for 3 consecutive nights. The first night was for adaptation and sleep apnea screening. Participants were then randomly assigned to either the structured foot bathing first (second night) and non-bathing second (third night) condition or the non-bathing first (second night) and foot bathing second (third night) condition.

Results

A footbath before sleep significantly increased and retained foot temperatures in both good and poor sleepers. The pattern of core temperatures during foot bathing was gradually elevated (poor sleepers vs. good sleepers = +0.40 ± 0.58 °C vs. +0.66 ± 0.17 °C). There were no significant changes in polysomnographic sleep and perceived sleep quality between non-bathing and bathing nights for both groups.

Conclusion

A footbath of 40 °C water temperature and 20-min duration before sleep onset increases foot temperatures and distal–proximal skin temperature gradients to facilitate vessel dilatation and elevates core temperature to provide heat load to the body. This footbath does not alter sleep in older adults with good and poor sleep.     

Effects of cerebral hypoperfusion on bispectral index: A randomised, controlled animal experiment during haemorrhagic shock

Background

The aim of this porcine haemorrhagic shock model was to investigate the changes of bispectral index (BIS) after slow and fast recovery of cerebral perfusion, and its correlation with plasma propofol concentrations.

Methods

After Animal Investigational Committee approval, 16 pigs during propofol anaesthesia underwent a liver trauma with severe hypotension, and were randomly assigned to receive therapy for either slow recovery (fluid resuscitation; slow group; n = 8) or fast recovery of cerebral perfusion (vasopressor combined with hypertonic-saline-starch; fast group; n = 8), respectively. Cerebral perfusion pressure (CPP = MAP − ICP), cerebral tissue oxygenation index (TOI), BIS, and plasma concentrations of propofol and haemoglobin were measured at baseline (Pre-shock), haemodynamic decompensation (Shock), and 5 (Therapy) and 30 min (End) after therapy, respectively.

Results

CPP, TOI, and BIS decreased significantly during shock (pre-shock vs. shock, fast: CPP: 65 ± 14 vs. 15 ± 4 mm Hg; TOI: 64 ± 6 vs. 47 ± 7%; BIS 60 ± 5 vs. 9 ± 10; slow: CPP: 60 ± 12 vs. 13 ± 7 mm Hg; TOI: 68 ± 7 vs. 49 ± 7%; BIS 63 ± 5 vs. 13 ± 12; P < 0.05). In the fast group, CPP, TOI, and BIS increased after therapy compared to the slow group (Therapy, fast: CPP: 47 ± 15 mm Hg, TOI: 61 ± 7%, BIS: 47 ± 21; slow: CPP: 18 ± 9 mm Hg, TOI: 51 ± 5%, BIS: 21 ± 19; P < 0.05). Propofol and haemoglobin concentrations were comparable between groups throughout the resuscitation phase.

Conclusions

In a haemorrhagic shock scenario, therapies with different impact on cerebral perfusion resulted in differing changes of BIS values, while plasma propofol and haemoglobin concentrations were comparable during the resuscitation phase; this suggests that BIS may also have reflected changes of cerebral perfusion.     

Change of impairment, disability and patient satisfaction after total knee arthroplasty in secondary care practice

Objectives

To assess the evolution of impairment and disability after total knee arthroplasty (TKA) for osteoarthritis and to seek an association with patient satisfaction with surgery.

Method

Consecutives patients (n = 45, 18 women) with osteoarthritis undergoing primary TKA in two secondary care inpatient clinics were prospectively assessed before one month and six months after surgery. Disability was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0-900) and the Lequesne Index (range 1-24). Patients’ perceived handicap was assessed on a visual analog scale (VAS, range 1-100). At one month and six months postoperatively, kinetic strength of quadriceps and hamstrings was obtained by isokinetics measures and patient satisfaction on a VAS (range 1-100).

Results

Mean age was 71.7 ± 7.0 years; mean duration of symptoms was 38.3 ± 33.4 months. Patient satisfaction was 83.9 ± 17.7 and 83.1 ± 22.4 at one month and six months after TKA, respectively. At one month, significant improvements were observed over baseline for pain (−30.73 ± 32.2; p < 0.01), physical function (Lequesne Index −2.28 ± 3.6, p < 0.01; and WOMAC score, −82.60 ± 148.5, p < 0.01), and patient perceived handicap (−21.84 ± 29.6, p < 0.01). A significant decrease in global knee range of motion was also observed. At six months, significant improvement was observed for pain (−47.96 ± 26.8; p < 0.01), physical function (Lequesne Index, −5.08 ± 3.66, p < 0.01; and WOMAC score, −157.04 ± 153.2, p < 0.01) and patient perceived handicap (−39.60 ± 24.1; p < 0.01). All isokinetics measures for quadriceps and hamstring were significantly improved between one month and six months after surgery. At one month and six months, the correlation between patient satisfaction and change in impairment, disability and patient perceived handicap was weak.

Discussion and conclusion

Impairment, disability and patient perceived handicap improved significantly after TKA for osteoarthritis. However, these improvements were poorly correlated with patient overall satisfaction with surgery.     

Osteoprotegerin: A new biomarker for impaired bone metabolism in complex regional pain syndrome?

Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50 ± 9.0 years; disease duration: 12 weeks [IQR 8–24]), 10 controls (6 women; mean age 58 ± 9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43 ± 15 years; time after fracture: 15 weeks [IQR: 6–22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P = 0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1–100.7]; controls: 46.7 pg/mL [IQR: 35.5–55.0]; P = 0.004; fracture patients: 45.9 pg/mL [IQR: 37.5–56.7]; P = 0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68–0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r = 0.391; P = 0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.     

The efficacy of a glial inhibitor,minocycline, for preventing persistent pain after lumbar discectomy: A randomized,double-blind,controlled study

Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. The minocycline group received 100 mg minocycline orally, twice daily, beginning the evening before surgery and continuing for 8 days. The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months. Secondary outcomes were pain intensity on movement, the incidence of persistent pain and chronic neuropathic pain, back pain intensity at rest and on movement, and changes in Neuropathic Pain Symptom Inventory, Brief Pain Inventory, and Roland-Morris scores at 3 months. An intention-to-treat analysis was performed for patients assessed from the day before surgery to 3 months. The decrease in lower limb pain intensity was similar in the placebo and minocycline groups, both at rest −1.7 ± 1.6 vs −2.3 ± 2.4 and on movement −2.5 ± 2.1 vs −3.4 ± 2.9. The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.     

Validation and properties of the verbal numeric scale in children with acute pain

Although the verbal numeric scale (VNS) is used frequently at patients’ bedsides, it has never been formally validated in children with acute pain. In order to validate this scale, a prospective cohort study was performed in children between 8 and 17 years presenting to a pediatric emergency department (ED) with acute pain. Pain was graded using the VNS, the visual analogue scale (VAS), and the verbal rating scale (VRS). A second assessment was done before discharge. We determined a priori that in order to be valid, the VNS would need to: correlate with the VAS (concurrent validity); decrease after intervention to reduce pain (construct validity); and be associated with the VRS categories (content validity). The VNS interchangeability with the VAS, its minimal clinically significant difference, and test–retest reliability were also determined. A total of 202 patients (mean age: 12.2 ± 2.6 years) were enrolled. The VNS correlated with the VAS: r_ic = 0.93, p < 0.001. There were differences in the VNS before versus after interventions (p < 0.001), and between VRS categories (mild versus moderate, p < 0.001; moderate versus severe, p < 0.001). The 95% limits of agreement (interchangeability) between VNS/VAS were outside the a priori set limit of ±2.0: −1.8, 2.5. The VNS minimal clinically significant difference was 1. The VNS had good test–retest reliability with 95% limits of agreement of −0.9 and 1.2. In conclusion, the VNS provides a valid and reliable scale to evaluate acute pain in children aged 8–17 years but is not interchangeable with the VAS.     

Hypokalemia during the cooling phase of therapeutic hypothermia and its impact on arrhythmogenesis

Background

Mild to moderate therapeutic hypothermia (TH) has been shown to improve survival and neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) as the presenting rhythm. This approach entails the management of physiological variables which fall outside the realm of conventional critical cardiac care. Management of serum potassium fluxes remains pivotal in the avoidance of lethal ventricular arrhythmia.

Methods

We retrospectively analyzed potassium variability with TH and performed correlative analysis of QT intervals and the incidence of ventricular arrhythmia.

Results

We enrolled 94 sequential patients with OHCA, and serum potassium was followed intensively. The average initial potassium value was 3.9 ± 0.7 mmol l⁻¹ and decreased to a nadir of 3.2 ± 0.7 mmol l⁻¹ at 10 h after initiation of cooling (p < 0.001). Eleven patients developed sustained polymorphic ventricular tachycardia (PVT) with eight of these occurring during the cooling phase. The corrected QT interval prolonged in relation to the development of hypothermia (p < 0.001). Hypokalemia was significantly associated with the development of PVT (p = 0.002), with this arrhythmia being most likely to develop in patients with serum potassium values of less than 2.5 mmol l⁻¹ (p = 0.002). Rebound hyperkalemia did not reach concerning levels (maximum 4.26 ± 0.8 mmol l⁻¹ at 40 h) and was not associated with the occurrence of ventricular arrhythmia. Furthermore, repletion of serum potassium did not correlate with the development of ventricular arrhythmia.

Conclusions

Therapeutic hypothermia is associated with a significant decline in serum potassium during cooling. Hypothermic core temperatures do not appear to protect against ventricular arrhythmia in the context of severe hypokalemia and cautious supplementation to maintain potassium at 3.0 mmol l⁻¹ appears to be both safe and effective.     

Circadian variation of human ventricular fibrillation dominant frequency

Aim

Circadian variation in human ventricular fibrillation (VF) dominant frequency is unknown. If present this would provide evidence of physiological influence on VF. The objective was to quantify the circadian variation in human VF dominant frequency.

Methods

Eight-lead Holter ECG recordings were obtained from a patient with severe myocarditis and chronic VF who was supported by a biventricular assist device. Recordings of up to 24 h duration were obtained on 6 days with an average interval between recordings of 7 days. Dominant frequency and amplitude were obtained using spectral analysis and assessed for (i) circadian (ii) inter-recording and (iii) inter-lead differences.

Results

There was a significant circadian variation in amplitude (night: 0.027 ± 0.004 mV Hz vs day: 0.044 ± 0.006 mV Hz, p < 0.0001) but not dominant frequency (night: 7.85 ± 0.62 Hz vs day: 7.93 ± 0.54 Hz, p > 0.05). There were significant differences between recordings in dominant frequency which ranged from 6.80 ± 0.29 Hz to 8.36 ± 0.38 Hz (p < 0.0001) and dominant frequency spectral amplitude which ranged from 0.033 ± 0.014 mV Hz to 0.043 ± 0.017 mV Hz (p < 0.0001). Histograms of dominant frequencies in leads exhibited strikingly different distributions, particularly in V2 that was characterised by a bimodal distribution, while the other leads were characterised by predominantly unimodal distributions.

Conclusion

VF dominant frequency spectral amplitude exhibited circadian variability. In a patient with severe myocarditis, supported with a biventricular assist device and in chronic VF, these results provide evidence for modulation of VF, probably induced by changes in posture and physical activity.     

Pain in chemotherapy-induced neuropathy – More than neuropathic?

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: −1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). “Anxiety” discriminated between painful and painless CIN; “CDT” and “anxiety” discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy.     

Efficacy of melatonin in the treatment of endometriosis: A phase II,randomized, double-blind,placebo-controlled trial

Endometriosis-associated chronic pelvic pain (EACPP) presents with an intense inflammatory reaction. Melatonin has emerged as an important analgesic, antioxidant, and antiinflammatory agent. This trial investigates the effects of melatonin compared with a placebo on EACPP, brain-derived neurotrophic factor (BDNF) level, and sleep quality. Forty females, aged 18 to 45 years, were randomized into the placebo (n = 20) or melatonin (10 mg) (n = 20) treatment groups for a period of 8 weeks. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain, dysmenorrhea, dysuria, and dyschezia (analysis of variance, P < 0.01 for all analyses). Post hoc analysis showed that compared with placebo, the treatment reduced daily pain scores by 39.80% (95% confidence interval [CI] 12.88–43.01%) and dysmenorrhea by 38.01% (95% CI 15.96–49.15%). Melatonin improved sleep quality, reduced the risk of using an analgesic by 80%, and reduced BNDF levels independently of its effect on pain. This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin’s ability to improve sleep quality. Additionally, the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms.