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Background Caused by a lesion or disease of the somatosensory system, neuropathic pain is notoriously difficult to treat with conventional analgesics. It has been suggested that inflammatory cytokines play a role in the development and maintenance of neuropathic pain. But human studies of these substances are relatively few and partly contradictory. Objectives To simultaneously investigate the plasma levels of chemokine interleukin 8 (IL-8) and the cytokines IL-6, IL-1 β, and Granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with peripheral neuropathic pain (most of whom due to failed back surgery syndrome) ( n = 14) compared to controls ( n = 17). Results IL-6 was significantly higher in patients than in controls (0.92 ± 0.12 pg/ml vs. 0.57 ± 0.08 pg/ml, p = 0.012). IL-1 ß, IL-8, and GM-CSF levels did not differ between the two groups. A multivariate analysis showed a tendency for patients also to have higher GM-CSF plasma levels than controls. Conclusions This study found an increased level of IL-6 in plasma in patients with neuropathic pain, but not for the other pro-inflammatory substances investigated. There are several possible confounders not registered or controlled for in this and other studies of neuropathic pain. Implications Larger studies that take several possible confounders into consideration are needed to further investigate the levels of plasma cytokines in different pain conditions.

Background Osteoarthritis (OA) of the knee is a common and increasingly prevalent condition that is one of the primary causes of chronic pain. Staying physically active protects against disability from knee OA but is also very challenging. A critical but unexamined question is whether patients at greatest risk for becoming less active are those with a genetic predisposition for greater sensitivity to daily pain. Aims We examined day-to-day variability in knee OA pain for patients with different variants of catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) single nucleotide polymorphisms (SNPs), and whether patients with a specific genotype experience more pain following daily physical activity. We predicted that patients having one or more copies of the Met 158 allele of COMT rs4680 (A-A or A-G) and one or more copies of the Asp 40 allele of OPRM1 rs1799971 (A-G or G-G) would show greater pain variability. We expected to see the same pattern for these SNPs with regard to moderation (i.e., exacerbation) of the activity-pain association. Methods A total of 120 knee OA patients reported on their pain 3 times per day over 22 days using handheld computers, and wore an accelerometer to capture daily physical activity. Multilevel modelling was used to examine the magnitude of within-person variability in pain by genetic group. We also examined whether lagged, within-patient associations between level of activity in the afternoon (i.e., minutes of moderate intensity activity, and number of steps) and knee pain at the end-of-day were moderated by between-patient differences in genotype. Results Regarding OPRM1 rs1799971 (Asn 40 Asp), patients with two copies of the Asn 40 allele showed the greatest day-to-day pain variability. Regarding COMT rs4680 (Val 158 Met), patients with the Val/Val genotype showed the greatest pain variability and also experienced the greatest increase in pain as a result of physical activity. A similar pattern of findings across bi-directional temporal lags was consistent with a negative feedback loop between daily physical activity and pain according to genotype. Consistent with some previous studies, there were no significant between-person differences in daily pain when comparing patients according to COMTrs4680, or OPRM1 rs1799971. Conclusions This study provides preliminary evidence that patients with certain genotypes for COMT rs4680 and OPRM1 rs1799971 ( G-G and A-A , respectively) experience more variability in their day-today pain and exacerbation of pain after daily physical activity compared to patients with other genotypes. Our findings should be replicated in larger study populations. Implications Previous clinical research has focused primarily on differences in average level of pain between patients with and without a specific genotype. Assessment of within-person variability through repeated measurements in daily life enhances the reliability, power, and ecological validity of phenotypic measurement. Perspective This study provides preliminary evidence that patients with certain variations in the COMT and OPRM1 SNPs experience more variability in their day-to-day pain and exacerbation of pain after daily physical activity.

Background Complex regional pain syndrome (CRPS) may occur following fractures, surgery or different trauma. Development of CRPS following snake-bite has only been published in three reports (from Turkey, Nepal and Korea), although snake bites occur frequently world-wide. There has been no report from Western Europe. Vipera Berus is a common snake in European countries and the only venomous snake in Norway. We here describe the development of CRPS in a young woman as a consequence of a viper bite (Vipera Berus) in the right arm. Methods We performed a clinical investigation (inspection, measurement of skin temperatures, sensory and motor evaluation) of the patient six months following the viper-bite, measurement of thermal thresholds (quantitative sensory testing, QST), measurement of resting sweat output (RSO) and quantitative sudomotor axon reflex (QSART) from both arms. Results The patient fulfilled the Budapest criteria for a CRPS-condition, with continuous pain and symptoms and findings of autonomic dysfunction. In addition, we found elevated thresholds of warmth and cold, evidence of an affection of afferent A-delta and C-fibres as well as an affection of the efferent sympathetic sudomotor C-fibres by QSART. An increased RSO-volume was in inverse relationship to the decreased QSART result. Conclusion and implications It is important to be aware of viper-bite as a possible eliciting event for CRPS for early diagnosis and treatment of a patient. As long-lasting pain and oedema are known complications, it is probable that CRPS after viper-bites previously may have been underdiagnosed. As many patients are unaware of being bit, viper bite should be considered in cases of unexplained sudden pain and swelling of a limb.

Background and aims Mirror visual feedback may be a useful clinical tool for reducing pain. Research suggests that reducing the size of a non-painful reflected hand can alleviate complex regional pain syndrome in the affected hand that is out of view. In contrast, research on healthy humans exposed to experimentally induced pain suggests that reducing the appearance of the size of a reflected body part can increase pain. The aim of this study was to investigate the effect of enlarging and reducing the visual appearance of the size of a hand using mirror visual feedback on pain threshold, intensity and tolerance in healthy human participants exposed to cold-pressor pain. Methods Participants were a convenience sample of 20 unpaid, healthy pain free volunteers aged 18 years or above. Each participant took part in one experiment where they completed cold-pressor pain tests whilst observing normal, enlarged and reduced size reflections of a hand congruent to a hand immersed in the ice cold water. A 4 × 2 factorial repeated measures analysis of variance (ANOVA) was performed on time to pain threshold and pain tolerance, and pain intensity with Condition (four levels: no reflection, reduced reflection, normal reflection, enlarged reflection) being the within-subject factors and Sex (two levels: female, male) between-subject factors. Results There were no significant effects for Condition, Sex, or Condition × Sex interaction for pain threshold, intensity or tolerance ( p > 0.05). There were no significant differences between the 3 mirror reflection conditions for agreement with the statements: “It felt like I was looking directly at my hand rather than at a mirror image”; “It felt like the hand I was looking at was my hand”; and “Did it seem like the hand you saw was a right hand or a left hand?”. Conclusion Enlarging or reducing the size of a hand using mirror visual feedback did not alter pain perception in healthy human participants exposed to cold-pressor pain. The different sizes of hands generated by mirror visual feedback created an illusion of looking at their own hand but this was not as strong as looking directly at the hand. Implications In future, investigators and clinicians using mirror visual feedback may consider including an adaptive phase to ensure the reflection has been perceptually embodied. Reasons for the lack of effects are explored to inspire further research in the field.

Background and aims Multimodal rehabilitation (MMR) programmes, including, physical training, educational and psychological interventions by an interdisciplinary team are found to be more successful for patients with disabling chronic pain compared with less comprehensive treatments. MMR programmes are based on the biopsychosocial model and the goal is usually to improve function, quality of life and facilitate and enable return to work. As pain clinics traditionally offer conventional medical pain treatment, there is limited knowledge about MMR given in this context. The aim of our study was to describe characteristics of patients with chronic pain, treated with a MMR programme at a conventional pain clinic, to evaluate patient-reported outcome measures (PROM) from start to one year after, and to study possibly associated factors for the improvement of health-related quality of life after one year. Methods A prospective, observational study with a one-year follow-up was performed. Subjects A total of 42 individuals (38 females, age 44.0 ± 12.3 years and 4 men age 40 ± 8.5 years) with different pain diagnoses were included. After a team assessment, the patients began a programme that lasted about three months. The MMR programme contained coordinated, individually adapted treatments administered individually or in groups, and was based on cognitive behavioural principles. Questionnaires regarding health-related quality of life (HRQoL) (EQ-5D), insomnia (ISI), mental health (HADS), painrelated disability (PDI), kinesiophobia (TSK), current pain intensity (VAS) and sense of coherence (SOC) were used at the start of the MMR and at follow-up. Demographic data were collected from the patient records. Results The PROM at baseline showed substantial pain problems with low HRQoL (EQ-5D index of 0.1 ± 0.282, and EQ VAS of 32.67 ± 20.1), moderate insomnia (ISI 18.95 ± 6.7), doubtful cases of depression and anxiety (HADS-depression 9.35 ± 4.1 and HADS-anxiety 9.78 ± 3.95), presence of pain-related disability (PDI 39.48 ±12.64), kinesiophobia (TSK 40.8 ± 9.8), as well as moderate current pain (VAS 61.31 ± 20.4). The sense of coherence was weak (SOC of 51.37 ± 14). At one-year follow-up, significant ( p ≥ 0.05) improvement occurred on the EQ-5D index, EQ VAS, ISI, PDI and TSK. In the logistic regression analysis, no significant associations could be identified. Conclusions MMR for patients with complex pain problems can be a successful treatment alternative at conventional pain clinics. Implications Since access to rehabilitation clinics in Sweden may be limited, the availability of MMR can increase by providing this type of intervention in pain clinics. Increased knowledge of MMR in different settings can also contribute to increased understanding and collaboration between pain clinics and rehabilitation units.

Objectives Quantification of intraepidermal nerve fibre density (IENFD) is an important small fibre measure in distal symmetric polyneuropathies (DSP), but quantitative evaluation of additional structural and functional factors may help in elucidating the underlying mechanisms, and in improving the diagnostic accuracy in DSP. The literature reports a weak or moderate relationship between IENFD and spontaneous and evoked pain in neuropathies, but the relationship between functional and structural small fibre parameters in patients with DSP is unclear. The objectives of the current study, therefore, were to determine morphological and functional parameters related to small nerve fibres in subjects with distal symmetric polyneuropathy (DSP) and healthy controls, and to characterize the interplay among these parameters in these two groups. Materials and Methods 17 patients with painful DSP (≤4 on 0-10 numerical rating scale) and with symptoms and signs of small fibre abnormality (with or without large fibre involvement) and 19 healthy control subjects underwent comprehensive functional and structural small fibre assessments that included quantitative sensory testing, response to 30 min topical application of 10% capsaicin and analysis of skin biopsy samples taken from the distal leg (IENFD, epidermal and dermal nerve fibre length densities (eNFLD, dNFLD) using global spatial sampling and axonal swelling ratios (swellings/IENFD and swellings/NFLD)). Results DSP patients had reduced sensitivity to cold (median -11.07°C vs. -2.60, P <0.001) and heat (median 46.7 vs. 37.70, P <0.001), diminished neurovascular (median 184 vs. 278 mean flux on laser Doppler, P =0.0003) and pain response to topical capsaicin (median 10 vs. 35 on 0-100 VAS, P =0.0002), and lower IENFD, eNFLD and dNFLD values combined with increased swelling ratios (all P < 0.001) compared to healthy controls. The correlation between structural and functional parameters was poor in DSP patients, compared with healthy controls. In healthy controls eNFLD and dNFLD, IENFD and eNFLD, IENFD and dNFLD all correlated well with each other ( r = 0.81; P < 0.001, r = 0.58; P = 0.009, r = 0.60; P = 0.007, respectively). In DSP, on the other hand, only eNFLD and dNFLD showed significant correlation ( r = 0.53, P = 0.03). A diagnostic approach of combined IENFD and eNFLD utilization increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%. Conclusions This study presents a rigorous comparison between functional and morphological parameters, including parameters such as eNFDL and dNFLD that have not been previously evaluated in this context. The correlation pattern between functional and structural small fibre parameters is different in patients with DSP when compared to healthy controls. The findings suggest a more direct relationship between structure and function of nerve fibres in healthy controls compared to DSP. Furthermore, the findings suggest that combining IENFD with measurement of NFLD improves the diagnostic sensitivity and specificity of DSP. Implications Combining small fibre parameters may improve the diagnostic accuracy of DSP.

Background and aims Peripheral neuropathic pain is described as a pain state caused by an injury or dysfunction of the nervous system, and could have clinical manifestations such as hyperalgesia, allodynia and spontaneous pain. The development of neuropathic pain may depend on long-term forms of neuronal plasticity in the spinal cord (SC). Expression of the immediate early gene proteins (IEGPs) Arc, Zif268, and c-Fos are implicated in establishment of long-term potentiation (LTP) induced by conditioning stimulation (CS) of primary afferent fibres. However, the impact of the neuropathic state (Bennett’s model) on CS-induced expression of IEGPs has not been studied. The aim of this study was to compare the levels of Arc, c-Fos and Zif268 immunoreactivity prior to and after conditioning stimulation in animals with developed neuropathic pain, with sham operated, non-ligated controls. Methods Twenty-four animals were divided equally into the neuropathic and non-neuropathic groups. Neuropathic pain was induced in all animals by conducting a loose ligation of the sciatic nerve with Chromic Catgut 4.0 sutures 7 days prior to conditioning stimulation or sham operation. The loose ligation was performed by placing sutures around the sciatic nerve compressing the nerve slightly just enough to reduce but not completely diminish the perineural circulation. A state of neuropathy was confirmed by a significant decrease in mechanical withdrawal threshold measured by von Frey’s fibres. Immunohisto-chemical analysis was performed on transverse sections obtained from the L3-L5 segments of the SC at 2 and 6 h post-CS and IEGP positive cells were counted in lamina I and II of the dorsal horn. During statistical analyses, the groups were compared by means of analysis of variance (univariate general linear model). If significant differences were found, each set of animals was compared with the sham group with post hoc Tukey’s multiple comparison test. Results Strikingly, all IEGPs exhibited a significant increase in immunoreactivity at both time points compared to time-matched, sham operated controls. Maximal IEGP expression was found 2 h after CS in neuropathic rats, and there was a smaller but still significant increase 6h after CS. The unstimulated side of the dorsal horn in stimulated animals did not show any significant change of the number of IEGP positive cells and was approximately at the same level as sham operated animals. The number of IEGP positive cells in sham operated controls (non-neuropathic and non-stimulated animals) showed same immunoreactivity in 2 and 6 h post sham operation. Conclusion and implications The neurophysiological process of neuropathic pain development is complex and needs to be studied further in order to clarify its nature and components. This present study is meant to reveal a step towards further understanding the role of Arc, c-Fos and Zif268 in neuropathic pain. Moreover, this study might contribute to the knowledge base for further research on better therapeutic possibilities for neuropathic pain.

Background Acute pain in response to injury is an important mechanism that serves to protect living beings from harm. However, persistent pain remaining long after the injury has healed serves no useful purpose and is a disabling condition. Persistent postsurgical pain, which is pain that lasts more than 3 months after surgery, affects 10–50% of patients undergoing elective surgery. Many of these patients are affected by neuropathic pain which is characterised as a pain caused by lesion or disease in the somatosen-sory nervous system. When established, this type of pain is difficult to treat and new approaches for prevention and treatment are needed. A possible contributing mechanism for the transition from acute physiological pain to persistent pain involves low-grade inflammation in the central nervous system (CNS), glial dysfunction and subsequently an imbalance in the neuron–glial interaction that causes enhanced and prolonged pain transmission. Aim This topical review aims to highlight the contribution that inflammatory activated glial cell dysfunction may have for the development of persistent pain. Method Relevant literature was searched for in PubMed. Results Immediately after an injury to a nerve ending in the periphery such as in surgery, the inflammatory cascade is activated and immunocompetent cells migrate to the site of injury. Macrophages infiltrate the injured nerve and cause an inflammatory reaction in the nerve cell. This reaction leads to microglia activation in the central nervous system and the release of pro-inflammatory cytokines that activate and alter astrocyte function. Once the astrocytes and microglia have become activated, they participate in the development, spread, and potentiation of low-grade neuroinflammation. The inflammatory activated glial cells exhibit cellular changes, and their communication to each other and to neurons is altered. This renders neurons more excitable and pain transmission is enhanced and prolonged.Astrocyte dysfunction can be experimentally restored using the combined actions of a μ–opioid receptor agonist, a μ–opioid receptor antagonist, and an anti-epileptic agent. To find these agents we searched the literature for substances with possible anti-inflammatory properties that are usually used for other purposes in medicine. Inflammatory induced glial cell dysfunction is restorable in vitro by a combination of endomorphine-1, ultralow doses of naloxone and levetiracetam. Restoring inflammatory-activated glial cells, thereby restoring astrocyte-neuron interaction has the potential to affect pain transmission in neurons. Conclusion Surgery causes inflammation at the site of injury. Peripheral nerve injury can cause low-grade inflammation in the CNS known as neuroinflammation. Low-grade neuroinflammation can cause an imbalance in the glial-neuron interaction and communication. This renders neurons more excitable and pain transmission is enhanced and prolonged. Astrocytic dysfunction can be restored in vitro by a combination of endomorphin-1, ultralow doses of naloxone and levetiracetam. This restoration is essential for the interaction between astrocytes and neurons and hence also for modulation of synaptic pain transmission. Implications Larger studies in clinical settings are needed before these findings can be applied in a clinical context. Potentially, by targeting inflammatory activated glial cells and not only neurons, a new arena for development of pharmacological agents for persistent pain is opened.

Background and aims Although neuropathic pain is known to negatively affect cognition, the neural mechanisms involved are poorly understood. Chronic pain is associated with changes in synaptic plasticity in the brain which may impact on cognitive functioning. The aim of this study was to model neuropathic pain in mid-aged rats using spinal nerve ligation (SNL). Following establishment of allodynia and hyperalgesia, behaviour was assessed in a battery of cognitive tests. Expression of the presynaptic protein, synaptophysin, and its colocalisation with the vesicular GABA and glutamate transporters (vGAT and vGLUT, respectively), was investigated in the medial prefrontal cortex (mPFC) and hippocampus. Methods Nine month old male Sprague Dawley rats underwent L5-L6 spinal nerve ligation or a sham procedure. Mechanical and cold allodynia and thermal hyperalgesia were assessed using von Frey, acetone and Hargreaves tests, respectively. Cognition was assessed in the novel-object recognition, air-puff passive avoidance and Morris water maze behavioural tasks. Immunohistochemistry was used to examine the expression of synaptophysin in the mPFC and CA1 region of the hippocampus and double labelling of synaptophysin and the vesicular transporters vGAT and vGlut was used to investigate the distribution of synaptophysin on GABAergic and glutamatergic neurons. Results SNL rats displayed impaired performance in the novel-object recognition task. Passive-avoidance responding, and spatial learning and memory in the Morris water maze, were unaffected by SNL surgery. However, in the water maze reversal task, pain-related impairments were evident during training and probe trials. SNL surgery was not associated with any differences in the expression of synaptophysin or its colocalisation with vGAT or vGLUT in the mPFC or the hippocampal CA1 region. Conclusions These results suggest that the SNL model of neuropathic pain is associated with deficits in recognition memory and cognitive flexibility, but these deficits are not associated with altered synaptophysin expression or distribution in the mPFC and CA1. Implications Cognitive complaints are common amongst chronic pain patients. Here we modelled cognitive impairment in a well-established animal model of neuropathic pain and investigated the neural mechanisms involved. A better understanding of this phenomenon is an important prerequisite for the development of improved treatment of patients affected.

Background and aim Glucocorticoids, a group of anti-inflammatory agents, are frequently administered in pain medicine. Of interest is the reported activity after intrathecal delivery in patients with neuropathic pain syndromes such as postherpetic neuralgia, though its efficacy is controversial. After the publication of two randomized clinical trials in postherpetic neuralgia patients treated with similar intrathecal methylprednisolone acetate (MPA) dosing regimes with conflicting results; one showing significant pain reduction (Kotani N, Kushikata T, Hashimoto H, Kimura F, Muraoka M, Yodono M, Asai M, Matsuki A: Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;23: 1514–9), the other increased pain sensations (Rijsdijk M, van Wijck AJ, Meulenhoff PC, Kavelaars A, van der Tweel I, Kalkman CJ: No beneficial effect of intrathecal methylprednisolone acetate in postherpetic neuralgia patients. Eur J Pain 2013;38:175–200), we decided additional research was warranted. Present study sought to determine effects of intrathecally delivered methylprednisolone on pain-like behaviour and pain-associated markers in three well established rodent pain models: (1) intraplantar carrageenan, (2) intraplantar formalin, and (3) ligation of L5/L6 spinal nerves (SNL model). Methods Male rats with intrathecal catheters were examined for (1) tactile allodynia after unilateral hindpaw intraplantar carrageenan injection (2%), (2) flinching and subsequent long term tactile allodynia after unilateral hindpaw intraplantar formalin injection (2.5%) or (3) tactile allodynia after unilateral ligation of the L5 and L6 spinal nerves. Rats were treated with the maximum tolerable intrathecal dose of the soluble methylprednisolone sodium succinate (MP) or the particulate methylprednisolone acetate (MPA). Dorsal root ganglia and spinal cords were harvested for immunohistochemistry to assess markers of neuronal damage (ATF3) and glial activation (GFAP, Iba1). Results During dose finding, severe generalized allodynia was observed with high intrathecal doses of both MPA and MP in naive rats. MPA had no effect upon tactile allodynia after carrageenan. MP and MPA did not reverse tactile allodynia in the SNL model, and did not reduce flinching in the formalin model. MP and MPA prevented the delayed (7–day) tactile allodynia otherwise observed in the formalin-injected paw. Systemic MP or perineural MP or MPA did not reduce pain-like behaviour in the SNL model. No reduction of neuronal injury (ATF3) in the dorsal root ganglion or astrocyte activation (GFAP) in the spinal dorsal horn with intrathecal MP or MPA was observed. There was a decrease in microglial activation (Iba1) in the spinal dorsal horn with MPA after SNL. Conclusion Severe generalized allodynia was observed after high intrathecal doses of MP and MPA in naive rats. No acute analgesic effects with intrathecal glucocorticoids were observed in three well established pain models. Only a late antiallodynic effect was present in the formalin model, 7 days after formalin injection and drug treatment. Implications Our results do not support use of intrathecal methylprednisolone in the treatment of pain.

ABSTRACT Purpose To investigate the effect of obesity on outcome in lumbar discectomy. Methods A cross-sectional postal survey; a self-made questionnaire, Beck depression inventory IA (BDI IA) and the Oswestry low back disability questionnaire (ODI) were sent to the patients, who had undergone lumbar disc surgery in the Oulu University Hospital between June 2005 and May 2008. Patients were divided into three groups according to BMI: normal, pre-obese and obese. The ODI was also examined in the framework of the international classification of functioning, disability and health (ICF) to investigate its ability to describe various dimensions of functioning (body structure and functions, activities and participation). Results The postal survey was sent to 642 patients, of whom 355 (55%) replied. Males dominated in the pre-obese (66%) and obese (62%) groups ( p = 0.01). Normal-weighted and pre-obese patients had lower BDI scores compared to obese patients (mean BDI: 8.0, 7.6,11.2, respectively, p = 0.035). Total ODI score was highest in the obese group compared to normal-weighted or pre-obese (20.3,18.6,26.4, respectively, p = 0.011). When ODI was linked to the ICF there were significant differences in all activity domains (mobility, self-care and interpersonal interactions and relationships) and the mobility component of the participation domain between the weight groups. Conclusions and implications Obesity has an impact on outcome in lumbar discectomy. Obese patients had higher scores in BDI and ODI indicating mild mood disturbances and moderate functional disability. According to ICF, functional disability of obese patients was observed to some extent in all activity domains. Obese patients will be more frequently present for disc surgery and increased morbidity risk must be recognized. We need a strategy to rehabilitate and activate obese patients pre- and postoperatively.

Background and aim Low back pain (LBP) is a debilitating problem worldwide causing disability and reducing quality of life. The Fear Avoidance Beliefs Questionnaire (FABQ) was developed on the basis of the assumption that fear-avoidance beliefs play a major role in LBP-related disability. It comprises 16 items scored by the patient and includes sub-scores for fear-avoidance beliefs regarding work and physical activity. This study aimed to translate and validate the Finnish version of the FABQ and to measure its properties among Finnish patients with LBP. Material and methods A forward-backward translation procedure was used based on modified recommended guidelines. The FABQ was applied to 66 Finnish patients with LBP. Patients answered the FABQ at baseline and again approximately two weeks later. The test-re-test reliability between the baseline and follow-up FABQwas evaluated by calculating intraclass correlation coefficients (ICC). Internal consistency between the items within total and sub-scores was evaluated by calculating Cronbach’s alpha. The items of the baseline FABQ were grouped using factor analysis and the correlations between the FABQ pain intensity in visual analogue scale (VAS) and Oswestry Disability Index (ODI) were assessed using linear regression analysis. Results The Finnish version of the FABQ was successfully adapted. The mean age of patients was 46. Almost all patients (97%) reported LBP, most patients (76%) had chronic pain lasting more than 3 months and the mean intensity of LBP was 58 mm on VAS. The follow-up time between the first and second questionnaire ranged from 2 days to 59 days with the median of 16 days. The ICC value for reliability between the baseline and follow-up questionnaires was excellent for the total score (0.91) and work sub-score (0.89), and good for the physical activity sub-score (0.73). The items regarding work showed high or excellent reliability throughout, with ICC values ranging from 0.63 to 0.89. The ICC values for the items related to physical activity ranged from 0.43 to 0.66, displaying moderate to good reliability. Cronbach’s alpha for internal consistency was excellent for the total score (0.92) and work (0.89), and good for physical activity (0.71). The best factor analysis solution yielded three factors characterized by the fear that pain aggravates due to (1) work or (2) physical activity, and (3) fear-avoidance beliefs concerning work. Higher total FABQ score was associated significantly with higher VAS (p-value 0.021) and ODI (<0.001). Conclusion and implications The expert committee successfully created an applicable Finnish versionof the FABQ. The Finnish FABQ is a valid and reliable instrument for assessing LBP patients’ fear avoidancebehaviour and has similar properties to those found in other validation studies of the FABQ. Thus it canbe used for assessing the risk of disability due to fear avoidance behaviour in Finnish-speaking patientswith LBP for both clinical and scientific purposes.

Background and aim Pain catastrophizing is linked to heightened pain and poorer coping among individuals with chronic pain, yet little is known about how pain catastrophizing associates with sleep and pain over the course of treatment for chronic pain. Previous research employing a cross-sectional design suggests that sleep mediates the association between pain catstrophizing and pain, but there have been no longitudinal studies examining the directionality of these associations. Thus, the aim of this study was to test two competing theoretical models. The first model specified that pain catastrophizing leads to increased pain via poor sleep. The second model specified that poor sleep leads to increased pain catastrophizing via increased pain. Methods This study examined the relations between pain catastrophizing, sleep, and pain among 50 consecutive patients (36 female, 14 male) ages 20–80 (M = 45.96, SD = 13.94) with chronic, non-malignant pain who were admitted to the Cleveland Clinic, Chronic Pain Rehabilitation Programme (CPRP). The CPRP, within the Neurological Centre for Restoration, Neurologic Institute at the Cleveland Clinic, is a comprehensive, interdisciplinary programme designed to treat patients with disabling chronic pain. As part of their daily, morning update with their case manager, patients completed self-report ratings of their previous night’s sleep time (TST), and their current pain, anxiety, and depression. Pain catastrophizing was assessed at admission and discharge. Results Over the course of treatment, daily TST increased from approximately 5 h and 20 min per night to nearly 6 h and 30 min per night, and average daily pain, daily depression, and daily anxiety decreased over the course of treatment. As the data in this study has a multilevel structure, with daily reports nested with in patients, we conducted multilevel path models to examine the longitudinal relations between pain catastrophizing, sleep, and pain. Multilevel path analysis permits the analysis of interdependent data without violating the assumptions of standard multiple regression. Models were conducted for pain catastrophizing and each of its subscales: rumination, magnification and helplessness. The findings were uniform across the composite pain catastrophizing scale and its subscales. There was an indirect path from sleep to pain catastrophizing (post-treatment) via pain, but not from pain catastrophizing (pre-treatment) to pain via sleep. There were also direct effects of sleep on pain and from pain to pain catastrophizing (post-treatment). Additionally, decreases in pain over the course of treatment were related to lower pain catastrophizing post-treatment. Conclusion and implications These results call into question previous evidence that pain catastrophizing indirectly affects pain by way of its impact on sleep. Rather, our findings suggest that pain mediates the relationship between sleep and levels of pain catastrophizing. These results therefore underscore importance and value in collecting longitudinal data and potential influence on the conclusions gained with regards to sleep, pain and psychological variables. These findings may be of clinical importance when tailoring interventions for individuals with chronic pain and perhaps even more so for those with comorbid pain and sleep disturbance; prioritizing the treatment of sleep difficulties could result in improvements to pain-related outcomes.