Human Studies

The pathophysiology of fibromyalgia includes central and peripheral factors. Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, are involved in peripheral and central nervous system development of pain and hyperalgesia. Few studies have examined circulating nerve growth factor and brain-derived neurotrophic factor in fibromyalgia or have investigated whether exercise interventions affect the levels of these peptides.

The aim of this systematic review with meta-analysis is to evaluate the clinical efficacy of transcutaneous electrical nerve stimulation (TENS) for any type of acute and chronic pain in adults.

Background and aims Patellofemoral pain (PFP) and patellofemoral joint osteoarthritis (PFJOA) are common non-self-limiting conditions causing significant pain and disability. The underlying pain pathologies lack consensus with evidence suggesting reduced pressure pain thresholds (PPTs) in adolescent females with PFP and individuals with knee osteoarthritis. A paucity of evidence exists for mixed-sex adults with PFP and PFJOA in isolation. Exploring if pain sensitisation is a dominant feature of PFP and PFJOA may have important implications for the delivery of a patient centred management approach. The primary aim was to measure local and remote PPTs in PFP and PFJOA patients compared to matched controls. Secondary aims were to evaluate the relationship between PPTs and (1) condition severity and (2) knee function. Methods 13 PFP patients plus 20 matched controls and 15 PFJOA patients plus 34 matched controls were recruited from a UK mixed-sex adult population. Controls were matched on age, sex and activity level. Demographic details, Tegner activity level score, symptom duration, condition severity (Kujala and KOOS-PF scores for PFP and PFJOA, respectively) and knee function (Modified Whatman score rating of five single leg squats) were recorded. PPTs were measured at six sites: five local around the knee, one remote on the contralateral leg. Between-group differences were tested using a two-way mixed model analysis of variance with repeated measures. Strength of association between PPTs and condition severity and knee function were tested using Spearman's rank order correlation. Results No statistically significant difference in PPTs were observed between the PFP patients [F(1,31) = 0.687, p = 0.413, η2 = 0.022] or PFJOA patients [F(1,47) = 0.237, p = 0.629, η2 = 0.005] and controls. Furthermore, no correlation was found between PPTs and condition severity or knee function in PFP or PFJOA (p > 0.05). Conclusions Results suggest mechanical pain sensitisation is not a dominant feature of UK mixed-sex adults with PFP or PFJOA. Implications PFP and PFJOA remain persistent pain complaints which may not be well explained by objective measures of sensitivity such as PPTs. The findings suggest that peripheral pain processing changes leading to pain sensitisation is not a key feature in PFP or PFJOA. Instead the underlying pain pathway is likely to remain primary nociceptive, possibly with a subgroup of patients who experience pain sensitisation and might benefit from a more targeted management approach.

Background and aims Chronic low back pain (chronic LBP) is the number one cause for years lived with disability among 301 diseases and injuries analyzed by The Global Burden of Disease study 2013. Insomnia is highly prevalent among people with chronic LBP. To explain the sleep-pain relationship, theoretical models propose that insomnia symptoms may be associated with increased basal inflammation, operationalized as c-reactive protein (CRP) and lead to further pain and disrupted sleep. We aimed to determine the associations between insomnia, chronic LBP, and inflammation (operationalized as CRP), whilst controlling for age, body mass index, smoking, physical activity, depression, anxiety and osteoarthritis. Methods A cross-sectional analysis of the third Nord-Trøndelag Health Study (2006-2008), a rural population survey of 50,666 participants in Norway aged 20-96 years. Insomnia (dichotomous) was defined according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition, and chronic LBP (dichotomous) as low back pain or stiffness lasting at least 3 months. Data for CRP were obtained from non-fasting serum samples and assessed via latex immunoassay methodology. We excluded participants with the following self-reported chronic somatic diseases: chronic heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis, fibromyalgia or ankylosing spondylosis. Possible associations between presence of insomnia and presence of chronic LBP (dependent), and the level of CRP and presence of chronic LBP (dependent), were assessed using logistic regression models. The possible association between insomnia and CRP (dependent) was assessed using linear regression. Multivariable analyses were conducted adjusting for confounders stated in our aim that achieved p ≤ 0.2 in univariate regressions. We performed stratified analyses for participants with "Normal" (<3 mg/L) "Elevated" (3-10 mg/L) and "Very High" (>10 mg/L) levels of CRP. Results In our total included sample (n = 30,669, median age 52.6, 54% female), 6.1% had insomnia (n = 1,871), 21.4% had chronic LBP (n = 6,559), and 2.4% had both (n = 719). Twenty four thousand two hundred eighty-eight (79%) participants had "Normal" CRP, 5,275 (17%) had "Elevated" CRP, and 1,136 (4%) had "Very High" CRP. For participants with "Normal" levels of CRP, insomnia was associated with higher levels of CRP (adjusted B = 0.04, 95%CI [0.00-0.08], p = 0.046), but not for people with "Elevated" or "Very High" levels of CRP. There was an association between CRP and presence of chronic LBP in the total sample (adjusted OR = 1.01, [1.00-1.01], p = 0.013) and for people with "Normal" CRP (1.05, [1.00-1.10, p = 0.034]. Insomnia was associated with the presence of chronic LBP in the total sample (adjusted OR = 1.99, 95%CI [1.79-2.21], <0.001) and for people with "Normal", "Elevated" and "Very High". Conclusions Individuals with insomnia have twice the odds of reporting chronic LBP. Insomnia, CRP and chronic LBP appear to be linked but the role of CRP appears to be limited. Longitudinal studies may help further explore the causal inference between insomnia chronic LBP, and inflammation. Implications Given the strong relationship between insomnia and chronic LBP, screening and management of comorbid insomnia and chronic LBP should be considered in clinical practice. Further longitudinal studies are required to explore whether the presence of insomnia and increased inflammation affects the development of chronic LBP.