The effect of cryotherapy on total antioxidative capacity in patients with active seropositive rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have increased oxidative stress, decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments are used to relieve joint inflammation and pain. Therefore, we measured the effect of cold treatments on the antioxidative capacity of RA patients with active disease. Sixty patients were randomized to (1) whole body cryotherapy at -110 °C, (2) whole body cryotherapy at -60 °C, or (3) local cryotherapy. Each treatment was given three times daily for 7 consecutive days in addition to the conventional rehabilitation. Blinded rheumatologist evaluated disease activity before the first and after the last cryotherapy. We collected plasma samples daily immediately before the first and after the second cryotherapy and measured total peroxyl radical trapping antioxidant capacity of plasma (TRAP), which reflects global combined antioxidant capacity of all individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI), adjusted for age, body mass index, disease activity, and dose of prednisolone, were 1244 (1098-1391) µM/l in the local cryotherapy, 1133 (1022-1245) µM/l in the cryotherapy at -60 °C, and 989 (895-1082) µM/l in the cryotherapy at -110 °C groups (p = 0.006). After the first treatment, there was a rise in 1-h TRAP of 14.2 (-4.2 to 32.6) µM/l, 16.1 (-7.4 to 39.6) µM/l, and 23.6 (4.1-43.2) µM/l, respectively. The increase was significant in the whole-body cryotherapy -110 °C group (p < 0.001) but not significant between the groups (p = 0.78). When analyzed for the whole week, the daily morning TRAP values differed significantly between the treatment groups (p = 0.021), but there was no significant change within each treatment group. Whole-body cryotherapy at -110 °C induced a short-term increase in TRAP during the first treatment session with but not during other treatment modalities. The effect was short and the cold treatments did not cause a significant oxidative stress or adaptation during 1 week.

Medication of inclusion body myositis: a systematic review.

To investigate the existing evidence on the effectiveness of approaches to treating inclusion body myositis and to assess the methodological quality of this evidence. The Cochrane Controlled Trials Register (CENTRAL), Medline, Embase, Cinahl, Physiotherapy Evidence (Pedro), McMaster and Web of Science databases were searched. The references of identified articles and reviews were also checked for relevancy. The methodological quality was assessed according to the Cochrane Collaboration's domain-based evaluation framework. Of the 331 identified records, 10 were considered relevant for a qualitative analysis. The risk of bias was considered being low for six studies and high for four. Eight studies were randomized controlled trials, and two were controlled clinical trials. In the samples, male gender predominated, and the mean age of the participants varied from 51 to 72 years. The duration of intervention varied from 3 to 17 months. One small trial on the effect of oxandrolone reported a significant positive result. The other trials observed no improvement or insignificant improvement among the participants treated with intravenous immunoglobulin, methotrexate, etanercept or interferon. Thus far, there is no evidence indicating that any specific treatment is the effective in treating inclusion body myositis.

Genetic and environmental influences on non-specific neck pain in early adolescence: a classical twin study.

BACKGROUND: Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. METHODS: Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11-12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. RESULTS: Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender and zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model fitting indicated that 68% (95% confidence interval 62-74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. CONCLUSIONS: Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors.

Acute cold stress in rheumatoid arthritis inadequately activates stress responses and induces an increase of interleukin 6.

OBJECTIVE: Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system. METHODS: A total of 55 patients with RA were recruited for whole-body cryotherapy at -110 degrees C and -60 degrees C, and local cold therapy between -20 degrees C and -30 degrees C for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy. RESULTS: In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after -110 degrees C cold stress followed by -60 degrees C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, -110 degrees C cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and -110 degrees C cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response. CONCLUSIONS: We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.

Effects of long-term whole-body cold exposures on plasma concentrations of ACTH, beta-endorphin, cortisol, catecholamines and cytokines in healthy females.

OBJECTIVE: Cold therapy is used to relieve pain and inflammatory symptoms. The present study was designed to determine the influence of long-term regular exposure to acute cold temperature. Two types of exposure were studied: winter swimming in ice-cold water and whole-body cryotherapy. The outcome was investigated on humoral factors that may account for pain alleviation related to the exposures. MATERIAL AND METHODS: During the course of 12 weeks, 3 times a week, a group of healthy females (n = 10) was exposed to winter swimming (water 0-2 degrees C) for 20 s and another group (n = 10) to whole-body cryotherapy (air -110 degrees C) for 2 min in a special chamber. Blood specimens were drawn in weeks 1, 2, 4, 8 and 12, on a day when no cold exposure occurred (control specimens) and on a day of cold exposures (cold specimens) before the exposures (0 min), and thereafter at 5 and 35 min. RESULTS: Plasma ACTH and cortisol in weeks 4-12 on time-points 35 min were significantly lower than in week 1, probably due to habituation, suggesting that neither winter swimming nor whole-body cryotherapy stimulated the pituitary-adrenal cortex axis. Plasma epinephrine was unchanged during both experiments, but norepinephrine showed significant 2-fold to 3-fold increases each time for 12 weeks after both cold exposures. Plasma IL-1-beta, IL-6 or TNF alpha did not show any changes after cold exposure. CONCLUSIONS: The main finding was the sustained cold-induced stimulation of norepinephrine, which was remarkably similar between exposures. The frequent increase in norepinephrine might have a role in pain alleviation in whole-body cryotherapy and winter swimming.

Characteristics of neck pain associated with adolescent headache.

The objective of the study was to find out what kind of neck pain (NP) is associated with headache (HA) and with various headache variables: frequency, type, intensity, disturbance, and relief with analgesics. A population-based sample of 12-year-olds with and without HA (n = 304) was followed for 4 years. At the age of 16 years, NP was evaluated on the basis of self-reported symptoms and a thorough physical examination of the neck region. Both self-reported and measured NP were associated with HA variables. Co-occurrent NP was found in adolescents with migraine as often as in those with tension-type HA. Especially, muscle pain and intensive, frequent NP were associated with disturbing HA unresponsive to analgesics. The study indicates that concomitant NP should be considered in adolescent HA sufferers, and a thorough cervical and muscle evaluation is recommended when planning the treatment of HA.

Does neck pain determine the outcome of adolescent headache?

The aim of the study was to examine the influence of concomitant neck pain (NP) on the outcome of headache (HA) frequency and HA type in adolescence. A population-based sample of 13-year-olds with or without HA (n = 228) was followed for 3 years. NP was evaluated at the beginning of the follow-up on the basis of recorded muscle tenderness and self-reported symptoms. During the 3 years of follow-up, changes in both HA type and frequency were common. NP interfering with daily activities at the age of 13 years predicted change from non-frequent (0-1/month) to monthly HA (>1/month), especially in boys (P = 0.03 boys, P = 0.06 girls). The use of physiotherapy predicted persistence of monthly HA in boys (P = 0.004). The changes in HA type were not predictable by NP. In conclusion, the risk of worsening HA in adolescence is more probable if the HA is associated with NP interfering with daily activities.

Adolescent disc degeneration--no headache association.

The objective of the study was to determine whether adolescents with headache have more disc degeneration in the cervical spine than headache-free controls. This study is part of a population-based follow-up study of adolescents with and without headache. At the age of 17 years, adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain less than once a month. MRI scans were interpreted independently by three neuroradiologists. Disc degeneration was found in 67% of participants, with no difference between adolescents with and without headache. Most of the degenerative changes were located in the lower cervical spine. In adolescence, mild degenerative changes of the cervical spine are surprisingly common but do not contribute to headache.

Is the report of widespread body pain associated with long-term increased mortality? Data from the Mini-Finland Health Survey.

OBJECTIVE: To determine whether an observation in a UK study, that persons with chronic widespread pain are at long-term increased risk of cancer mortality, can be replicated in a different setting. METHODS: Subjects were participants aged >or=30 yrs in the Mini-Finland Health Survey conducted between 1979 and 1980. Information collected included prevalent pains at different joints throughout the body, demographic, anthropometric, lifestyle and occupational factors. During follow-up, until 1994, information on vital status and cause of death was obtained. RESULTS: 7182 persons participated (89.8%). The prevalence of widespread body pain (pain at four or more sites) was 20% in females and 12% in males, and during follow-up there were a total of 1647 deaths. The risk of death was not elevated amongst those with widespread pain [relative risk (RR): 0.86; 95% confidence interval (CI): 0.74-1.00], and in particular, those with widespread pain were at a slightly lower risk of several disease-specific causes of death and cancer death (RR: 0.64; 95% CI: 0.46-0.91). CONCLUSIONS: This study of multiple pains has not confirmed a previous observation of an association between the reporting of widespread pain and subsequent increased risk of cancer death. Differences in the definitions used or, more probably, the population studied, in particular, a larger rural population with more multiple pains related to physical activity may account for the differences.

Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. A randomised single blinded controlled trial.

OBJECTIVE: Local cryotherapy is used to relieve pain and inflammation in injuries and inflammatory conditions. Whole-body cryotherapy is an extreme method administered at -110 degrees C for 2 to 3 minutes. The aim of the study was to compare the effect of cryotherapies on pain and inflammation in patients with rheumatoid arthritis (RA). METHODS: Sixty patients with active seropositive RA were recruited in a randomised controlled single-blinded study to receive whole-body cryotherapy at -110 degrees C, whole-body cryotherapy at -60 degrees C, application of local cold air at -30 degrees C and the use of cold packs locally. In the final analysis, the last 2 groups were pooled. The patients had 2-3 cryotherapy sessions daily for one week plus conventional physiotherapy. Clinical and laboratory variables and patient's and physician's global assessments were used to assess the outcome. Disease activity was calculated by DAS. RESULTS: Pain decreased in all treatment groups, most markedly in the whole-body cryotherapy (-110 degrees C) group. DAS decreased slightly with no statistically significant differences between the groups. No serious or permanent adverse effects were detected. Six of 40 patients (15%) discontinued the whole-body cryotherapy. CONCLUSION: Pain seemed to decrease more in patients in the whole-body cryotherapy at -110 degrees C than during other cryotherapies, but there were no significant differences in the disease activity between the groups. However, cryotherapy at -110 degrees C is expensive and available only in special centres and may have minor adverse effects. Based on our results, whole-body cryotherapy at -110 degrees C is not superior to local cryotherapy commonly used in RA patients for pain relief and as an adjunct to physiotherapy.

Lung function after acute and repeated exposures to extremely cold air (-110 degrees C) during whole-body cryotherapy.

Whole-body cryotherapy (WBC) is one mode of cold therapy, during which rheumatic patients are exposed to very cold air (-110 degrees C) in minimal clothing. It is also proposed to have a bronchodilatory effect. The aim was to examine the effects of WBC on lung function in healthy humans after acute and repeated exposures. Twenty-five healthy, non-smoking subjects participated in the study. They were exposed to WBC for 2 min three times per week for 12 weeks. The peak expiratory flow rate (PEF) and forced expiratory volume in 1 s (FEV1) were measured before and after (at 2 and 30 min) the first WBC, and then similarly at 4, 8 and 12 weeks. At all time points, after 30 min of the WBC the PEF values were slightly lower compared with values before the WBC, and the reductions reached statistical significance at 1 month (5.1 +/- 1.2%), and at 3 months (3.2 +/- 1.7%). After 30 min of the first WBC, the FEV1 was significantly reduced by 2.3 +/- 0.8%, but no other changes were observed during the study. In conclusion, the WBC induced minor bronchoconstriction in healthy humans instead of proposed bronchodilatation. The WBC seems not to be harmful for lung function, but should be used with caution in susceptible individuals.

Adolescent flexibility, endurance strength, and physical activity as predictors of adult tension neck, low back pain, and knee injury: a 25 year follow up study.

OBJECTIVE: To examine whether adolescent flexibility, endurance strength, and physical activity can predict the later occurrence of recurrent low back pain, tension neck, or knee injury. METHODS: In 1976, 520 men and 605 women participated in a sit and reach test (flexibility) and a 30 second sit up test (endurance strength). In 1976 and 2001 (aged 37 and 42 years) they completed a questionnaire. Lifetime occurrence and risk of self reported low back pain and self reported, physician diagnosed tension neck and knee injury were calculated for subjects divided into tertiles by baseline results of strength and flexibility tests. RESULTS: Men from the highest baseline flexibility tertile were at lower risk of tension neck than those from the lowest tertile (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.28 to 0.93). Women from the highest baseline endurance strength tertile were at lower risk of tension neck than those from the lowest tertile (OR 0.60, 95% CI 0.40 to 0.91). Men from the highest baseline endurance strength tertile were at higher risk of knee injury than those from the lowest tertile (OR 1.96, 95% CI 1.05 to 3.64). Men who at school age participated in physical activity were at lower risk of recurrent low back pain (OR 0.61; 95% CI 0.42 to 0.88) than those who did not. CONCLUSIONS: Overall good flexibility in boys and good endurance strength in girls may contribute to a decreased risk of tension neck. High endurance strength in boys may indicate an increased risk of knee injury.

Acute and long-term effects of winter swimming and whole-body cryotherapy on plasma antioxidative capacity in healthy women.

The effects of severe cold stress on total peroxyl radical trapping antioxidant capacity of plasma (TRAP) were studied in two groups of healthy women: a whole-body cryotherapy group (WBC, n = 10) and a winter swimming group (WS, n = 10). The biovariability of TRAP values was also analysed. The WBC group was exposed to -110 degrees C for 2 min, whereas the exposure for the WS group lasted 20 s in ice-cold water. Sessions were organized three times per week for 12 weeks. Blood specimens were collected at 2, 4, 8 and 12 weeks at rest, 2 and 35 min after the cold exposures and at the corresponding times without cold exposure on a separate day. Conventional methods were used to determine TRAP values. The between-subject variation was 13.6% and the within-subject variation 6.4%. The index of individuality was 0.46, and the index of heterogeneity was 0.079. These results indicate a marked heterogeneity among subjects. During the first 4 weeks, the mean TRAP value significantly increased at 2 min after cold exposure in the WBC group, returning to baseline 35 min after the exposure. Similar changes were observed in the WS group. However, all changes due to cold were relatively mild (<5%). After 4 weeks no changes in TRAP values after the cold exposures were noticed and no long-term changes in basal TRAP values were observed. In the main, regular WBC and WS do not seem to be harmful as far as plasma antioxidative capacity is concerned.

Muscle tenderness in pericranial and neck-shoulder region in children with headache. A controlled study.

Increased pericranial muscle tenderness is connected with tension-type headache in adults. In children, the importance of muscle tenderness in the pericranial or neck-shoulder region in the pathogenesis of different types of headache is unknown. The present study evaluated muscle tenderness in the pericranial and neck-shoulder region in children with migraine, those with tension-type headache and those without headache. An unselected population-based questionnaire study concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years. Of them, 183 children were randomly selected for a face-to-face interview and a clinical examination. Muscle tenderness was recorded by manual palpation and dolorimeter. Children with migraine had increased overall tenderness, recorded by manual palpation, compared with those without headache. They also self-reported tenderness in the neck-shoulder region during daily activities more often than the children of the other groups. Muscle tenderness was not associated with paediatric tension-type headache. The mean pressure pain thresholds did not differ among the three groups. However, a negative correlation between the total tenderness score and the dolorimeter score was found in each group. In conclusion, children with migraine had increased muscle tenderness at palpation of the pericranial and neck-shoulder muscles and they also reported pain symptoms in the neck-shoulder region most frequently. Instead, increased pericranial and neck-shoulder muscle tenderness was not associated with tension-type headache in children.

Widespread pain among 11-year-old Finnish twin pairs.

OBJECTIVE: To examine the prevalence of widespread musculoskeletal pain (WSP) symptoms in 11-year-old Finnish twins and to determine the relative role of genetic and environmental factors in the etiology of WSP. METHODS: Data on current pain items were collected from 1995 to 1998 from a national sample of Finnish families with 11-year-old twins born between 1984 and 1987. The presence of WSP was determined using a validated questionnaire method. Pairwise similarity was computed for 583 monozygotic (MZ) pairs, 588 same-sex dizygotic (DZ) pairs, and 618 opposite-sex DZ twin pairs. Variance components for genetic and environmental factors were estimated using biometric structural equation modeling techniques. RESULTS: The prevalence of WSP was 9.9%, with no sex difference. The majority of twin pairs with WSP were discordant. The tetrachoric correlations for male MZ (r = 0.38), male DZ (r = 0.37), female MZ (r = 0.59), female DZ (r = 0.54), and opposite-sex pairs (r = 0.43) showed little difference by zygosity. Female pairs were more concordant than male pairs among both MZ and DZ twins. Biometric model-fitting indicated that genetic factors did not account for the pattern of twin similarity. Among boys 35%, and among girls 56%, of the variation in liability to WSP could be attributed to shared familial environmental effects. The remainder was attributed to unshared environmental effects. CONCLUSION: Genetic factors seem to play at most a minor role in WSP in 11-year-old twins, and environmental factors shared by family members account for a substantial proportion of the variability in WSP.

Comorbidity of other pains in schoolchildren with migraine or nonmigrainous headache.

OBJECTIVE: To compare the occurrence of pain other than headache in prepubertal children with migraine and those with nonmigrainous headache. STUDY DESIGN: An unselected population-based prospective follow-up study on the occurrence of headache in school-aged children was carried out in 1290 children aged 8 to 9 years. The children (n = 725) who reported headache during the preceding 6 months were sent a more detailed questionnaire concerning the occurrence of pain other than headaches; 622 children (86%) returned an acceptably completed second questionnaire. Of them, 53 (8.5%) had migraine. Nonmigrainous headache was found in 460 children (74%). RESULTS: Children with migraine reported neck-shoulder pain, abdominal pain, back pain, and otalgia significantly more often than those with nonmigrainous headache. The median of the sum of other pains in children with migraine was significantly higher than that in children with nonmigrainous headache. The sum of other pains correlated positively with the frequency of nonmigrainous headache episodes (r =.40; 95% CI.31-.47), but there was no correlation between the sum of other pains and frequency of migraine attacks (r = -0.09; 95% CI -0.36-0.20). CONCLUSION: Children with migraine are more likely to report types of pain other than headaches, regardless of the frequency of attacks. Children with frequent nonmigrainous headaches also report higher frequencies of other types of pain.

Widespread pain and neck pain in schoolchildren. A prospective one-year follow-up study.

The aims of this study were to prospectively follow up population-based cohorts of children with widespread pain, children with neck pain and pain-free children, in order to evaluate 1-y changes in pain symptoms and to evaluate predictors for persistent widespread pain and for the change of neck pain to widespread pain. A structured pain questionnaire, the Children's Depression Inventory, and a sleep questionnaire were completed by the pre-adolescent cohorts, and clinical evaluation with tender point palpation and pain threshold measurements was carried out in both years. The Child Behavior Checklist, the Teacher's Report Form and a sociodemographic questionnaire were completed at baseline. More children in the 2 pain cohorts reported pain at follow-up than did controls (p < 0.0001). Children with persistent widespread pain had lower pain thresholds compared with those whose pain classification changed. In the neck pain group, 19 (20.4%) reported widespread pain at follow-up. Although depressive symptoms and sleep problems were associated with the change of neck pain to widespread pain, neither they nor other measured factors showed independent explanatory power in multiple logistic regression analysis. In conclusion, fluctuation of pain symptoms occurred mainly among pain cohorts. Depressive and sleep problems may have an effect on the spreading of regional neck pain to widespread pain. Pain threshold measurement and evaluation of depressive and sleep problems may be useful tools for secondary prevention of musculoskeletal pain in pre-adolescents.

One year outcome of preadolescents with fibromyalgia.

OBJECTIVE: Twenty-two children with fibromyalgia (FM), found in a population based study of 1756 Finnish preadolescents, were prospectively and blindly followed for one year to investigate their physical and psychological background factors and to determine the one year persistence of FM. METHODS: The American College of Rheumatology 1990 criteria for FM were used. Widespread pain was determined with a structured, pretested pain questionnaire, including items on disability both at baseline and at followup. At baseline, hypermobility was tested with Beighton's method and aerobic capacity with a 20 m shuttle run test, and psychological data were collected using the Children's Depression Inventory (CDI), a sleep questionnaire, and the Child Behavior Checklist and Teacher's Report Form. At followup, evaluations with the CDI and sleep questionnaire were repeated. RESULTS: At baseline, the prevalence of FM was 1.3% (95% CI 0.8 to 1.9). At followup, 16/22 (73%) children were available for evaluation; 4 (25%) had persistent FM. Children with FM had low pain thresholds. Only one of 19 children had hypermobility. Those with persistent FM had persistent subjective disability. Depressive symptoms diminished, but there was still comorbidity of pain and depressive symptoms at followup. CONCLUSION: This study supports a previous one, in which FM in children had a good outcome. However, fluctuation of pain symptoms in children might partly explain the outcome. Children with persistent FM showed persistent disability with a number of distress symptoms.