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This prospective longitudinal study of 80 patients analysed the effect of preoperative pain catastrophizing, anxiety, depression and sense of coherence on the Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, quality of life, grip strength and range of motion during the first year after salvage surgery for wrist osteoarthritis. Generalized estimating equations were used to analyse the effect of the psychological factors on the outcome variables. Pain catastrophizing or a tendency for anxiety preoperatively had a strong negative impact on postoperative Disabilities of the Arm, Shoulder and Hand and Patient-Rated Wrist Evaluation. Anxiety also predicted a lower postoperative quality of life, whereas pain catastrophizing had a negative impact on grip strength. Sense of coherence did not influence the outcome. Level of evidence: II

Background and aims Although literature concerning chronic pain patients indicates that cognitive behavioural variables, specifically acceptance and fear of movement/(re)injury, are related to life impact, the relative roles of these factors in relation to pain characteristics (e.g. intensity and spreading) and emotional distress are unclear. Moreover, how these variables affect rehabilitation outcomes in different subgroups is insufficiently understood. This study has two aims: (1) to investigate how pain, cognitive behavioural, and emotional distress variables intercorrelate and whether these variables can regress aspects of life impact and (2) to analyse whether these variables can be used to identify clinically meaningful subgroups at baseline and which subgroups benefit most from multimodal rehabilitation programs (MMRP) immediately after and at 12-month follow-up. Methods Pain aspects, background variables, psychological distress, cognitive behavioural variables, and two life impact variables were obtained from the Swedish Quality Registry for Pain Rehabilitation (SQRP) for chronic pain patients. These data were analysed mainly using advanced multivariate methods. Results The study includes 22,406 chronic pain patients. Many variables, including acceptance variables, showed important contributions to the variation in clinical presentations and in life impacts. Based on the statistically important variables considering the clinical presentation, three clusters/subgroups of patients were identified at baseline; from the worst clinical situation to the relatively good situation. These clusters showed significant differences in outcomes after participating in MMRP; the subgroup with the worst situation at baseline showed the most significant improvements. Conclusions Pain intensity/severity, emotional distress, acceptance, and life impacts were important for the clinical presentation and were used to identify three clusters with marked differences at baseline (i.e. before MMRP). Life impacts showed complex relationships with acceptance, pain intensity/severity, and emotional distress. The most significant improvements after MMRP were seen in the subgroup with the lowest level of functioning before treatment, indicating that patients with complex problems should be offered MMRP. Implications This study emphasizes the need to adopt a biopsychosocial perspective when assessing patients with chronic pain. Patients with chronic pain referred to specialist clinics are not homogenous in their clinical presentation. Instead we identified three distinct subgroups of patients. The outcomes of MMRP appears to be related to the clinical presentation. Thus, patients with the most severe clinical presentation show the most prominent improvements. However, even though this group of patients improve they still after MMRP show a complex situation and there is thus a need for optimizing the content of MMRP for these patients. The subgroup of patients with a relatively good situation with respect to pain, psychological distress, coping and life impact only showed minor improvements after MMRP. Hence, there is a need to develop other complex interventions for them.

Background Long-term sick-leave due to stress-related ill-health is increasing in several economically developed countries. Even though different forms of interventions are administered in regular care for stress-related disorders, such as Stress-induced Exhaustion disorder (SED), the scientific evidence for the effectiveness of such treatments is sparse. The objective of this study was to explore changes in SED-symptoms and return-to-work-rates in a large group of SED-patients participating in a standardized Multimodal intervention (MMI) in a clinical setting. Method This open clinical trial tracked 390 patients who fulfilled the criteria for SED undergoing a 24-week MMI, including return-to-work-strategies. Before inclusion, all patients underwent a multi-professional assessment by a team of licensed physicians, licensed psychologists, and licensed physiotherapists. Self-rated questionnaires were administered before treatment, at treatment-start, mid-treatment, post-treatment, and at 12-month follow-up. Within-group change was evaluated over time with mixed-effects models. Beyond different symptoms, working time, sick-leave compensation, and adverse effects were also measured. Results There were significant improvements in symptoms of SED, burnout, anxiety, depression, and insomnia, with large within-group effect sizes (d = 0.91–1.76), improvements that were maintained at 12-month follow-up. Furthermore, there was a significant increase in quality of life and large improvements in average working time and sick-leave compensation. Some adverse effects were reported, mainly concerning an increase in stress, anxiety, and worry. Conclusion SED-patients participating in this standardized MMI reported large symptom alleviation, increased working time and reduced sick-leave compensation, indicating a beneficial treatment. There were some adverse effects, but no more so than other psychological treatments. This study confirms previous findings that high levels of depression and anxiety decrease to sub-clinical levels during treatment, while symptoms of SED also decline, yet still persists above sub-clinical levels at 12-month follow-up. On the whole, this open clinical trial suggests that a standardized MMI, administered in a clinical setting, improves symptoms and return-to-work rates in a clinically representative SED-population. Trial registration This study was registered on Clinicaltrials.gov 2017.12.02 (Identifier: NCT03360136).

Refugees, and more so women than men, are often seeking medical care for a wide range of health-related problems, among which persistent pain has long been recognized as a defining feature. When treating refugee women for any condition, pain and its consequences need to be addressed in the rehabilitation efforts. It is therefore essential that health professionals engaged in the care of refugee women are familiar with the physiology of pain mechanisms, including the biopsychosocial model of pain, as well as the best evidence-based practice in managing pain, acute as well as chronic. Persistent or chronic pain not only causes disability and restricted functioning but also produces psychological impairments, compounding the impact on overall personal and social functioning. Yet, the research literature on health regarding refugees is predominantly targeted at mental health problems without specific reference to pain and pain as a significant cause of distress and disability due to migration (pre-and post). Pain as a consequence of torture is also an issue that is under-assessed when refugees are seeking medical aid for pain-related problems. When aiming at treating refugee women with disabling pain, one can use the same intervention methods that are being used for other chronic pain states. Professionals need, however, to be able to work with less written information and in close co-operation with interpreters. Reviews of the rehabilitation literature have noted a lack of scientifically rigorous studies of multicomponent interventions for refugees. Only few studies have evaluated outcomes of pain management, and the quality of the evidence they provide is very low. The small number of randomized controlled trials and the resulting paucity of information means that recommendations amounting to good clinical practice for refugee women with persistent pain are lacking. The aim of this article, illustrated by two patient cases, is to point out important areas that need to be addressed within the health care system in order to improve health care for refugee women. Pain is a common reason for refugee women to seek medical aid, is a costly burden for the society, and decreases quality of life for these women.

Objective To describe the frequency of reported sleeping, depression and pain problems, the severity of these problems and the degree of self-estimated difficulties in mental functions and activities in relation to the sleep disturbance and pain category group in patients on long-term sick-leave. Design Cross-sectional study. Patients A total of 1206 patients experiencing difficulty in resuming work. Methods Patient examinations by specialists in psychiatry, orthopaedic surgery and rehabilitation medicine. Validated questionnaires, including status regarding depression, sleep, pain and functioning were used. Results The prevalence of sleep disturbance was 83%; 74% of the patients with moderate/severe sleep disturbance also had moderate/severe pain problems and 26% had no/mild pain problems. Fifty-seven percent of the patients with no/mild sleep disturbance and 83% of the patients with moderate/ severe sleep disturbance also had depression. The degree of difficulty in performing the 6 selected International Classification of Functioning, Disability and Health activities and mental functions was higher for the category with moderate/severe sleep problems, compared with those with no/mild sleep problems. Conclusion To optimize rehabilitation for patients on long-term sick-leave experiencing difficulties in returning to work, the results indicate a need also to focus attention on sleep problems and not only on pain and depression. This may entail the planning of measures to improve decision-making and concentration and alleviate lassitude, fatigability, sadness and pessimistic thoughts.

Provoked vestibulodynia is a common cause of superficial dyspareunia in young women. Recent evidence has pointed out the importance of studying endogenous pain modulation in these women. An impairment of diffuse noxious inhibitory controls (DNIC) has been suggested in chronic pain conditions with a female predominance such as fibromyalgia and temporomandibular disorder. Our aim was to examine whether patients with provoked vestibulodynia and healthy women with or without combined oral contraceptives (COC) display a DNIC response to cold noxious stimulation. Twenty patients with provoked vestibulodynia not using COC, 20 healthy women on COC and 20 healthy women without COC were included and tested days 7-11 of their menstrual cycle. Pressure pain thresholds (PPTs) and pain ratings using VAS were measured on the arm and leg before and during a cold pressor test. A socio-medical questionnaire, the Hospital and Anxiety Depression Scale and the Short Form-36 were completed. The majority of the subjects in all three study groups significantly increased their PPTs during cold noxious stimulation indicating a DNIC response. The patients displayed lower PPTs compared to the healthy women. Depression, anxiety and bodily pain were more often reported by the patients. No differences related to the intake of COC were observed between the healthy women. In conclusion, women with provoked vestibulodynia as well as healthy women irrespective of COC status display a DNIC response indicating an endogenous pain inhibition. However, the results imply a systemic hypersensitivity in women with vestibulodynia with low general pain thresholds as compared to healthy women.

Objective: To compare the effect of acupuncture with placebo transcutaneous electrical nerve stimulation (TENS) when added to the exercise treatment of rotator cuff tendinitis with respect to pain, shoulder movements and function. Design: Prospective alternate allocation controlled trial. Setting: Outpatient department. Patients: Thirty-three patients (12 women and 21 men) were included in the study. All had clinically diagnosed rotator cuff tendinitis. Intervention: Both groups underwent a standardized training programme. Each patient received in addition either 10 treatments with acupuncture or placebo TENS, 1-2 times per week. Main outcome measures: The parameters investigated were intensity of pain (measured with visual analogue scale), active, passive as well as functional movements in the shoulder (hand in neck (HIN) and pour out of a pot (POP)). Patients were tested before treatment, after treatment and at a six-month follow-up. Medicine intake, ability to lie on the affected side and sleep disturbances were evaluated. A subjective assessment was made after the treatment and at follow-up. Results: Sixteen patients had acupuncture, 17 placebo TENS. Eight patients endured pain at rest in the placebo TENS group, and 10 in the acupuncture group. After treatment both groups improved, the improvement persisted at the six-month follow-up. Both groups increased range of movement. Except for the functional test HIN in the acupuncture group, there were no differences between the groups regarding other parameters investigated directly after treatment or at six-month follow-up. Conclusion: There is no difference between the effect of additional acupuncture treatment and placebo TENS in the treatment of rotator cuff tendinitis.

The number of patients with difficulty in resuming work after long-term sick leave has increased in several European countries including Sweden. The general aim of this study was a comprehensive description - based on multidisciplinary diagnostics and assessments - of patients with the common feature of marked difficulty in resuming working life after a long absence. A particular aim was to elucidate the possible effect of comorbidity on pain descriptors, disability, quality of life, assessed working ability and rehabilitation needs. Six hundred and thirty-five long-term sick leavers were referred from National Insurance Offices and consecutively accepted for investigation. Several self-report questionnaires were used. All patients were examined by three board-certified specialist physicians in psychiatry, orthopaedic surgery and rehabilitation medicine, respectively. Fifty-five percent of the patients had psychiatric-somatic comorbidity. The three most frequent combinations of diagnoses in the comorbidity group were fibromyalgia/myalgia and depressive episode, fibromyalgia/myalgia and recurrent depression, spinal pain and depressive episode, whereas the three most frequent in those with psychiatric diagnosis only were depressive episode, recurrent depression, phobias/anxiety. Differences in pain descriptors and in difficulties with activities were found among the three groups. All had lower health-related quality of life than references. Only one-sixth had no assessed working capacity and only 3% were assessed as able to resume work without rehabilitation; 80% were multidisciplinarily assessed as needing rehabilitation. Patients with psychiatric diagnoses, with or without concomitant somatic diagnoses, need medical rehabilitation or medical/vocational rehabilitation in combination to a greater extent than patients with somatic diagnoses only. This implies that medical rehabilitation programmes ought to adapt increasingly to the needs of patients with psychiatric-somatic comorbidity.

Calcitonin gene-related peptide (CGRP), but not substance P (SP), was found to inhibit edema-promoting actions of inflammatory mediators (histamine, leukotrine B4, 5-hydroxytryptamine) in vivo in the hamster cheek pouch, human skin, and rat paw. The effect of CGRP was present in the low nanomolar dose range, and it was mimicked by activation of sensory nerves with capsaicin which caused release of endogenous CGRP-like immunoreactivity (IR). The findings provide new information on the potential impact of sensory nerve activation during inflammatory processes by indicating that sensory nerves may play an anti-inflammatory role.

To correlate changes in vestibular pain thresholds to general pain thresholds in a subgroup of women with provoked vestibulodynia taking part in a treatment study.Thirty-five women with provoked vestibulodynia were randomized to 4 months' treatment with either electromyographic biofeedback (n=17) or topical lidocaine (n=18). Vestibular and general pressure pain thresholds (PPTs) were measured and the health survey Short Form-36 (SF-36) was filled out before treatment and at a 6-month follow-up. Subjective treatment outcome and bodily pain were analyzed. Thirty healthy women of the same age served as controls for general PPTs and SF-36.No differences in outcome measures were observed between the 2 treatments. Vestibular pain thresholds increased from median 30 g before to 70 g after treatment in the anterior vestibule (P0.001) and from median 20 to 30 g in the posterior vestibule (P0.001). PPTs on the leg and arm were lower in the patients as compared with controls both before and at the 6-month follow-up. Patients reporting total cure were 3/35; 25/35 were improved. The number of patients who frequently reported of other bodily pain was reduced after the treatment. The patients had lower scores for SF-36 (General Health, Vitality) before treatment, which was restored at the 6-month follow-up.Treating provoked vestibulodynia by either topical lidocaine or electromyographic biofeedback increased vestibular pain thresholds, reduced dyspareunia, and improved bodily pain. The patients showed a general hypersensitivity to pressure pain compared with controls and in this study the hypersensitivity did not seem to be affected by treating the superficial dyspareunia.

The release of neuropeptide Y (NPY) is reported to increase in ischemic conditions and may thus be involved in chronic myalgia. The purpose of this study was to investigate the effect of isometric contraction on intramuscular levels of NPY in relation to local pain development.Intramuscular microdialysis was performed in the masseter and trapezius muscles to determine NPY levels before, during, and after isometric contraction in 16 healthy females. Pain intensity was assessed simultaneously with VAS. Repeated measures ANOVA, t-test, and Pearson correlation analysis were used for statistical analyses.The level of NPY in the trapezius muscle was increased during and after contraction, while there was no change in the masseter muscle. The level of NPY before contraction was higher in the masseter muscle than in the trapezius muscle, and the levels in the two muscles were correlated before and during contraction. Low-level pain in both muscles after probe insertion increased significantly during contraction, but the pain was not correlated to the NPY level.Pain is developed in the trapezius and masseter muscles during repeated isometric contraction. The NPY level is increased in the trapezius muscle but is not associated with the pain development.

Background. To evaluate the efficacy of electromyographic biofeedback and topical lidocaine treatment for women with vulvar vestibulitis. Methods. A prospective randomized study where 46 women with vulvar vestibulitis were randomized to receive either electromyographic biofeedback or topical lidocaine treatment for four months. Assessments with vulvar pressure pain thresholds and questionnaires regarding quality of life, psychosocial adjustments, and sexual functioning were made before treatment, after treatment, and at six- and 12-month follow-ups. Nonparametric statistical methods were used to analyze differences in outcomes. Results. Nine women (9/46) dropped out during the treatment period. Both treatments showed significantly improved values for vestibular pressure pain thresholds, quality of life measurements, and sexual functioning at the 12-month follow-up. No differences were found between the two treatment groups. No severe side effects were reported. Conclusions. Four months’ treatment with electromyographic biofeedback and topical lidocaine gave statistically significant improvements on vestibular pain measurements, sexual functioning, and psychosocial adjustments at the 12-month follow-up. No differences in outcome between the two treatments were observed but a larger sample may be needed to obtain significance. The treatments were well tolerated but the compliance to the electromyographic biofeedback training program was low. A combination of both treatments could potentially benefit many women with vulvar vestibulitis.

Vulvar vestibulitis syndrome (VVS) is a long lasting disorder of superficial dyspareunia in young women. Quantitative sensory testing, including mechanical and temperature pain thresholds and warm/cold difference limen (WCL), was performed in the vestibular mucosa in 22 women (mean age 25.0 years) with vestibulitis and 20 control subjects (mean age 25.6 years). The tests were carried out on days 7-11 of the menstrual cycle. Patients had allodynia to mechanical testing with von Frey filaments, 14.3+/-3.1mN in the symptomatic posterior area as compared with 158+/-33.5mN in healthy subjects, P0.0001. The pain threshold to heat was 38.6+/-0.6 degrees C in patients and 43.8+/-0.8 degrees C in controls, P0.0001. In addition, pain threshold to cold was 21.6+/-1.2 degrees C in patients whereas cooling down to 6 degrees C was usually not painful in controls. WCL was 4.9+/-0.5 degrees C in patients and 9.6+/-1.5 degrees C in healthy subjects, P0.01. The results are compatible with the hypothesis that patients with VVS have an increased innervation and/or sensitization of thermoreceptors and nociceptors in their vestibular mucosa.

The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

The effects of experimentally induced ischaemia after free-flap surgery on concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) were studied in flap tissue and in different regions of the rat brain (striatum, hippocampus, pituitary, hypothalamus, frontal and occipital cortex). Ten days after the operation, CGRP-LI and NKA-LI were decreased in the ischaemic tissue but increased in the surrounding tissue. In the brain, CGRP-LI was increased in five of six regions analysed, with the exception of the striatum. SP-LI and NKA-LI were increased in the pituitary and hippocampus, but decreased in other brain regions. Changes of CGRP-LI in the brain correlated positively with the CGRP-LI concentrations in the surrounding flap tissue and the CGRP-LI concentrations in the ischaemic flap tissue with the extent of flap survival. The results of the present study suggest that higher concentrations of CGRP-LI are related to tissue survival and that endogenous CGRP has a regulatory effect in ischaemia.

1. Recent work in our laboratory has demonstrated that intrathecal administration of a selective antagonist of calcitonin gene-related peptide (CGRP), CGRP8-37, increased the hindpaw withdrawal latency (HWL) to thermal stimulation and hindpaw withdrawal threshold (HWT) to pressure in normal rats, and that these effects were more pronounced than in rats with mononeuropathy. 2. The present study was performed to investigate the effects of intrathecal administration of CGRP8-37 on the HWL and HWT in rats with unilateral hindpaw inflammation induced by subcutaneous injection of carrageenin. The effect of naloxone was also studied. 3. Subcutaneous injection of 0.1 ml of carrageenin into the plantar region of the left hindpaw induced a significant increase in the volume of the ipsilateral hindpaw (P < 0.001), and significant bilateral decreases of the HWL to thermal stimulation (ipsilateral: P < 0.001; contralateral: P < 0.01) and HWT to pressure (ipsilateral: P < 0.001; contralateral: P < 0.01). 4. Intrathecal administration of 10 nmol of CGRP8-37, but not of 1 or 5 nmol, induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation (thermal test: P < 0.001; mechanical test: P < 0.001). 5. The effect of intrathecal administration of 10 nmol CGRP8-37 on HWL and HWT was significantly more pronounced in intact rats than in rats with experimentally induced inflammation (ipsilateral: P < 0.001; contralateral: P < 0.001). 6. The effect of CGRP8-37 on withdrawal responses in the inflamed paw was partly reversed by intrathecal injection of naloxone at a dose of 88 nmol in the thermal (ipsilateral: P < 0.01; contralateral: P = 0.14) and mechanical tests (ipsilateral: P < 0.05; contralateral: P = 0.60). 7. A significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws was demonstrated 24 h after unilateral injection of carrageenin (ipsilateral: P < 0.001; contralateral: P < 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P < 0.001), but not in plasma (P = 0.75). 8. The present study demonstrates that acute experimentally-induced unilateral hindpaw inflammation, induces bilateral increases in the amount of CGRP-like immunoreactivity in hindpaw perfusates. Intrathecal administration of CGRP8-37 increased the HWL to thermal stimulation and HWT to pressure bilaterally. 9. The results indicate that CGRP plays a role in the transmission of presumed nociceptive information in the spinal cord of rats with experimentally induced inflammation. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.