Regulation of inflammatory arthritis by the upstream kinase mitogen activated protein kinase kinase 7 in the c-Jun N-Terminal kinase pathway

Musculoskeletal pain is common across all populations and costly in terms of impact on the individual and, more generally, on society. In most health-care systems, the first person to see the patient with a musculoskeletal problem such as back pain is the general practitioner, and access to other professionals such as physiotherapists, chiropractors, or osteopaths is still either largely controlled by a traditional medical model of referral or left to self-referral by the patient. In this paper, we examine the arguments for the general practitioner-led model and consider the arguments, and underpinning evidence, for reconsidering who should take responsibility for the early assessment and treatment of patients with musculoskeletal problems.     

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study,Norway

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995–97 and in 2006–08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.     

Predictions of co-contraction depend critically on degrees-of-freedom in the musculoskeletal model

In biomechanics, the calculation of individual muscle forces during movements is based on a model of the musculoskeletal system and a method for extracting a unique set of muscle forces. To obtain a unique set of muscle forces, non-linear, static optimisation is commonly used. However, the optimal solution is dependent on the musculoskeletal geometry, and single joints may be represented using one, two or three degrees-of-freedom. Frequently, a system with multiple degrees-of-freedom is replaced with a system that contains a subset of all the possible degrees-of-freedom. For example, the cat ankle joint is typically modelled as a planar joint with its primary degree-of-freedom (plantar-dorsiflexion), whereas, the actual joint has three rotational degrees-of-freedom. Typically, such simplifications are justified by the idea that the reduced case is contained as a specific solution of the more general case. However, here we demonstrate that the force-sharing solution space of a general, three degrees-of-freedom musculoskeletal system does not necessarily contain the solutions from the corresponding one or two degrees-of-freedom systems. Therefore, solutions of a reduced system, in general, are not sub-set solutions of the actual three degrees-of-freedom system, but are independent solutions that are often incompatible with solutions of the actual system. This result shows that representing a three degrees-of-freedom system as a one or two degrees-of-freedom system gives force-sharing solutions that cannot be extrapolated to the actual system, and vice-versa. These results imply that general solutions cannot be extracted from models with fewer degrees-of-freedom than the actual system. They further emphasise the need for precise geometric representation of the musculoskeletal system, if general force-sharing rules are to be derived.     

Doctors' rights and patients' obligations

Marshall examines arguments for and against physicians breaching their duty of confidentiality to persons diagnosed with HIV or AIDS by notifying third parties such as sexual partners or general practitioners who give care unrelated to HIV or AIDS. The arguments presuppose that the confidentiality right is not absolute, but may give way under certain circumstances. A physician's obligations to the larger community, for instance, may outweigh the obligation to keep a diagnosis of AIDS or HIV confidential. Marshall also argues that physicians who incur risks by treating patients with AIDS or HIV have a right to knowledge that will help them protect themselves. A patient with AIDS or HIV may be obliged to reveal this fact to physicians when seeking care for other health problems, or to allow the diagnosing physican to do so. These arguments may have implications for the debate over testing patients for AIDS or HIV without consent.     

The No!—Or the Yes and the How—of Sex for Patients with Neck,Back and Radicular Pain Syndromes

The restrictions imposed upon sexual activity by neck, back and radicular pain syndromes are of serious concern to the patient. In recent years the subject of When, and even How is raised with increasing frequency, and the patient expects the physician to reply with appropriate answers.The reply must be tempered by the level of the patient''s recovery, the evaluation of what other activities the patient can perform without pain or with minimal pain and the method to be used. Sexual activity may precipitate recurrent pain or aggravate existing pain in the same manner as lifting, pushing, pulling or any other physical activity, if performed too early or too vigorously in the course of recovery from neck, back or radicular pain syndromes.In dealing with the problem of recovery from painful musculoskeletal or neuromuscular states, timing is of the utmost importance. Unless a timetable is specifically outlined, recurrences are common, and the condition may become chronic. The inability of the patient to deal satisfactorily with the sexual aspect of his daily living may, in itself, lead to emotional tensions and guilt feelings which may delay or prevent recovery.There is need to handle this problem at every level of the involvement in order to achieve a desirable end result—namely, the absence of pain and its replacement with pleasure.     

Use of acupuncture in equine reproduction

The goal of this review is to provide evidence supporting the physiologic basis for the use of acupuncture as a treatment in equine reproduction, and to discuss current uses of acupuncture for the treatment of anestrus, urine pooling, uterine infection and/or fluid, infertility, maintenance of pregnancy, cryptorchidism, musculoskeletal pain, and poor libido in stallions. The benefits achieved through acupuncture treatment are thought to be a result of hormonal regulation, altered smooth muscle motility, and general stress and/or pain relief from musculoskeletal or environmental conditions.     

Frequency and severity of musculoskeletal symptoms in humans during an outbreak of trichinellosis caused by Trichinella britovi

Musculoskeletal symptoms such as myalgia are well-known features in the course of trichinellosis; however, the characteristics of musculoskeletal findings have been described in detail in only 1 study. The present study was aimed to determine the joint and muscle symptoms in subjects diagnosed with acute trichinellosis at our rheumatology unit during a Trichinella britovi outbreak that occurred in Izmir, Turkey, in 2004. In total, 98 patients (55 females, 43 males; mean age 32.3 +/- 10.9 yr) were included in the study. A detailed history and full musculoskeletal examination were obtained in each patient. A self-administered questionnaire developed for recording the musculoskeletal symptoms was completed monthly until all the symptoms were resolved. Pain at the joints, restriction of movements (in shoulders, elbows, wrists, knees, ankles, and temporomandibular joints), myalgia, and muscle weakness (neck and shoulder girdle, muscles of the upper and forearm, back, thigh, and calf muscles) were assessed in every patient. Eosinophil counts, serum levels of creatine kinase, and lactate dehydrogenase also were analyzed. The most frequent musculoskeletal symptoms were muscle pain (86 cases [87.8%]), joint pain (83 [84.7%]), subjective muscle weakness (75 [76.5%]), and restriction of joint movements (63 [64.3%]). Calves, upper arm, neck and shoulder girdle, and forearms were the most affected muscle groups. Muscle pain was reported more frequently in the upper than in the lower extremities and during activity. The most frequent painful joints were shoulders, knees, wrists, and ankles. Upper extremity joints were affected more frequently than the lower extremity joints (77.6 vs. 70.4%). Joint pain occurred more frequently at rest. Both muscle weakness and restriction of joint movements were reported in and around the most frequently affected regions. No evidence of arthritis and objective muscle weakness was noted on physical examination in any patient. Musculoskeletal symptoms in the course of T. britovi infection are frequent but with an excellent prognosis. Joint pain in people suffering from acute trichinellosis may occur more frequently than reported previously.     

The pain-adaptation model: a discussion of the relationship between chronic musculoskeletal pain and motor activity

Articles describing motor function in five chronic musculoskeletal pain conditions (temporomandibular disorders, muscle tension headache, fibromyalgia, chronic lower back pain, and postexercise muscle soreness) were reviewed. It was concluded that the data do not support the commonly held view that the pain of these conditions is maintained by some form of tonic muscular hyperactivity. Instead, it seems clear that in these conditions the activity of agonist muscles is often reduced by pain, even when this does not arise from the muscle itself. On the other hand, pain causes small increases in the level of activity of the antagonist. As a consequence of these changes, force production and the range and velocity of movement of the affected body part are often reduced. To explain how such changes in the behaviour come about, we propose a neurophysiological model based on the phasic modulation of excitatory and inhibitory interneurons supplied by high-threshold sensory afferents. We suggest that the "dysfunction" that is characteristic of several types of chronic musculoskeletal pain is a normal protective adaptation and is not a cause of pain.     

Musculoskeletal disorders: primary and secondary interventions.

In the United States alone, the annual cost associated with the diagnosis and care of musculoskeletal trauma amounts to tens of billions of dollars [Occupational Musculoskeletal Disorders: Function, Outcomes and Evidence. Lippincott Williams and Wilkins, Philadelphia]. Moreover, these costs are continuing to increase at an alarming rate. In fact, in the United States today, occupational musculoskeletal disorders are the leading causes of work disability. Changes in health care policy and demand for improved allocation of health care resources by the Federal government have also recently placed greater pressure on health care professionals to provide the most cost-effective treatment for these disorders, as well as to validate treatment effectiveness. Indeed, treatment-outcome monitoring has assumed new importance in medicine. It is particularly essential in musculoskeletal care, which is currently targeted for attention by health care planners because of its high cost and perceived traditional inefficient care. With these facts in mind, the purpose of the present article is to review the status of current primary and secondary interventions for musculoskeletal disorders. Before doing so, a brief discussion of the biopsychosocial model of pain and disability, which is currently the most heuristic approach to intervention, will be provided.     

Prevalence of Self-Reported Pain,Joint Complaints and Knee or Hip Complaints in Adults Aged ≥ 40 Years: A Cross-Sectional Survey in Herne,Germany

Background

Pain and musculoskeletal complaints are among the most common symptoms in the general population. Despite their epidemiological, clinical and health economic importance, prevalence data on pain and musculoskeletal complaints for Germany are scarce.

Methods

A cross-sectional survey of a random sample of citizens of Herne, Germany, aged ≥ 40 years was performed. A detailed self-complete postal questionnaire was used, followed by a short reminder questionnaire and telephone contacts for those not responding. The questionnaire contained 66 items, mainly addressing pain of any site, musculoskeletal complaints of any site and of knee and hip, pain intensities, the Western Ontario MacMaster Universities (WOMAC) index, medication, health care utilization, comorbidities, and quality of life.

Results

The response rate was 57.8% (4,527 of 7,828 individuals). Survey participants were on average 1.3 years older, and the proportion of women among responders tended to be greater than in the population sample. There was no age difference between the population sample and 2,221 participants filling out the detailed questionnaire. The following standardized prevalences were assessed: current pain: 59.7%, pain within the past four weeks: 74.5%, current joint complaints: 49.3%, joint complaints within the past four weeks and twelve month: 62.8% and 67.4%, respectively, knee as the site predominantly affected: 30.9%, knee bilateral: 9.7%, hip: 15.2%, hip bilateral: 3.5%, knee and hip: 5.5%. Pain and musculoskeletal complaints were significantly more often reported by women. A typical relationship of pain and joint complaints to age could be found, i.e. increasing prevalences with increasing age categories, with a drop in the highest age groups. In general, pain and joint pain were associated with comorbidity and body mass index as well as quality of life.

Conclusions

Our data confirm findings of other recent national as well as European surveys. The high site specific prevalences of knee and hip complaints underline the necessity to further investigate characteristics and consequences of pain and symptomatic osteoarthritis of these joints in adults in Germany.     

ONTOLOGY OR PHENOMENOLOGY? HOW THE LVAD CHALLENGES THE EUTHANASIA DEBATE

This article deals with the euthanasia debate in light of new life‐sustaining technologies such as the left ventricular assist device (LVAD). The question arises: does the switching off of a LVAD by a doctor upon the request of a patient amount to active or passive euthanasia, i.e. to ‘killing’ or to ‘letting die’? The answer hinges on whether the device is to be regarded as a proper part of the patient's body or as something external. We usually regard the switching off of an internal device as killing, whereas the deactivation of an external device is seen as ‘letting die’. The case is notoriously difficult to decide for hybrid devices such as LVADs, which are partly inside and partly outside the patient's body. Additionally, on a methodological level, I will argue that the ‘ontological’ arguments from analogy given for both sides are problematic. Given the impasse facing the ontological arguments, complementary phenomenological arguments deserve closer inspection. In particular, we should consider whether phenomenologically the LVAD is perceived as a body part or as an external device. I will support the thesis that the deactivation of a LVAD is to be regarded as passive euthanasia if the device is not perceived by the patient as a part of the body proper.     

Electrical stimulation of peripheral and central pathways for the relief of musculoskeletal pain

One method for the treatment of chronic musculoskeletal pain involves stimulation of the peripheral or central nervous system. Such stimulation includes transcutaneous electrical nerve stimulation, dorsal column stimulation, and deep brain stimulation. This review discusses the clinical use of electrical stimulation for the relief of musculoskeletal pain, and describes the results of studies conducted in our laboratory suggesting that such stimulation reduces pain transmission along sensory-discriminative pathways.     

Musculoskeletal discomfort and feeling of fatigue among female professional workers: the need for ergonomics consideration.

Subjective feeling of general fatigue and physiological strain were studied in one hundred female professional employees of industrial worker and full-time nurses. Using an interview questionnaire the feeling of fatigue were studied. The subjects were asked to indicate on the body diagram all the areas of musculoskeletal pain from which they perceived discomfort. Furthermore physical strength test consisting of grip test, back and leg strength test were carried out before and after work on all subjects. The results indicated that the two groups of employees showed different symptoms of "pain" and/or "fatigue," with regard to the different parts of body. It was also noted that the physical strength after work was lower for both groups as compared to before work and even lower for the industrial workers than the nurses. The feeling of fatigue between the two investigated groups was not significantly different, but for the musculoskeletal pain was highly significantly different. The worker group used also more pain-killing drugs for releasing the muscle pain. It was evident that ergonomics intervention for female professional workers was of great importance and urgency, particularly for making the workplace more human. Improvement of the working conditions, better organization of work, and ergonomics interventions are suggested as necessary measures for reduction of pain and feeling of discomfort.     

Development and Validation of the Keele Musculoskeletal Patient Reported Outcome Measure (MSK-PROM)

Objective

To develop and validate a patient report outcome measure (PROM) for clinical practice that can monitor health status of patients with a range of musculoskeletal (MSK) disorders.

Methods

Constructs for inclusion in the MSK-PROM were identified from a consensus process involving patients with musculoskeletal conditions, clinicians, purchasers of healthcare services, and primary care researchers. Psychometric properties of the brief tool, including face and construct validity, repeatability and responsiveness were assessed in a sample of patients with musculoskeletal pain consulting physiotherapy services in the United Kingdom (n=425).

Results

The consensus process identified 10 prioritised domains for monitoring musculoskeletal health status: pain intensity, quality of life, physical capacity, interference with social/leisure activities, emotional well-being, severity of most difficult thing, activities and roles, understanding independence, and overall impact. As the EuroQol (EQ-5D-5L) is a widely adopted PROMs tool and covers the first four domains listed, to reduce patient burden to a minimum the MSK-PROM was designed to capture the remaining six prioritised domains which are not measured by the EQ-5D-5L. The tool demonstrated excellent reliability, construct validity, responsiveness and acceptability to patients and clinicians for use in clinical practice.

Conclusion

We have validated a brief patient reported outcome measure (MSK-PROM) for use in clinical practice to measure musculoskeletal health status and monitor outcomes over time using domains that are meaningful to patients and sensitive to change. Further work will establish whether the MSK-PROM is useful in other musculoskeletal healthcare settings.     

Concordance of sleep and pain outcomes of diverse interventions: an umbrella review

Background/Objective

Pain influences sleep and vice versa. We performed an umbrella review of meta-analyses on treatments for diverse conditions in order to examine whether diverse medical treatments for different conditions have similar or divergent effects on pain and sleep.

Methods

We searched published systematic reviews with meta-analyses in the Cochrane Database of Systematic Reviews until October 20, 2011. We identified randomized trials (or meta-analyses thereof, when >1 trial was available) where both pain and sleep outcomes were examined. Pain outcomes were categorized as headache, musculoskeletal, abdominal, pelvic, generic or other pain. Sleep outcomes included insomnia, sleep disruption, and sleep disturbance. We estimated odds ratios for all outcomes and evaluated the concordance in the direction of effects between sleep and various types of pain and the correlation of treatment effects between sleep and pain outcomes.

Results

151 comparisons with 385 different trials met our eligibility criteria. 96 comparisons had concordant direction of effects between each pain outcome and sleep, while in 55 the effect estimates were in opposite directions (P<0.0001). In the 20 comparisons with largest amount of evidence, the experimental drug always had worse sleep outcomes and tended to have worse pain outcomes in 17/20 cases. For headache and musculoskeletal pain, 69 comparisons showed concordant direction of effects with sleep outcomes and 36 showed discordant direction (P<0.0001). For the other 4 pain types there were overall 27 vs. 19 pairs with concordant vs. discordant direction of effects (P = 0.095). There was a weak correlation of the treatment effect sizes for sleep vs. headache/musculoskeletal pain (r = 0.17, P = 0.092).

Conclusions

Medical interventions tend to have effects in the same direction for pain and sleep outcomes, but exceptions occur. Concordance is primarily seen for sleep and headache or musculoskeletal pain where many drugs may both disturb sleep and cause pain.     

Killing, letting die and moral perception: a reply to Grant Gillett

A number of philosophers in recent times have employed arguments to show that there is no morally relevant difference between killing a patient and allowing that patient to die in those circumstances where the outcome is virtually identical and where death is preventable, at least for a significant time. From his perspective as both a philosopher and a clinician, Grant Gillett has rejected such general and abstract arguments in the light of the intuitions and moral perceptions available to clinicians and those who care for the terminally ill. I argue that his strategy fails, is massively question-begging, and that his appeal to the notion of 'moral particularism', far from being an alternative to cogent philosophical argument, actually supports the very position he has attempted to discredit.     

New insights into pain-related changes in muscle activation revealed by high-density surface electromyography

High-density surface electromyography (HDEMG) is an electrophysiological technique that can be used to quantify the spatial distribution of activity within muscles. When pain-free individuals perform sustained or repetitive tasks, different regions within a muscle become progressively more active; this is thought to reflect a strategy to redistribute the load to different regions, thus limiting localised muscle fatigue. The use of HDEMG has revealed that when people with musculoskeletal pain perform the same tasks, the distribution of activity within the same muscle is usually different, and the same muscle region tends to be active throughout the whole task without progressive activation of different muscle regions. This potentially results in a focal overload of a muscle region, and may contribute to fatigue, localised muscle pain and potentially pain persistence and/or recurrence over time. Interestingly, not all patients with musculoskeletal pain present with this regional alteration in muscle activation, reflecting the heterogeneity of patient presentations. This article will briefly review the technique of HDEMG followed by a review of studies demonstrating spatial redistribution of muscle activity in asymptomatic people during both isometric and dynamic conditions, including functional tasks. Lastly, the article will provide a review of HDEMG studies with a focus on changes in the behaviour of the lumbar erector spine and upper trapezius in people with spinal pain. These studies have revealed subtle changes in the distribution of muscle activity in people with spinal pain, which may have relevance for onset, persistence or recurrence of symptoms and could become a target of novel therapeutic approaches.     

Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis

AIM: To investigate whether blood serotonin (5-hydroxytryptamine) (5-HT) modulates musculoskeletal pain differently in seropositive and seronegative rheumatoid arthritis (RA). METHODS: Patients with temporomandibular joint (TMJ) involvement of seropositive RA (33 patients) or seronegative RA (28 patients) and 26 healthy individuals were included. TMJ pain, general musculoskeletal pain, plasma and serum 5-HT, acute phase reactants and thrombocyte count were investigated. RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001). There was no significant correlation between serum and plasma levels of 5-HT in any group. In the seropositive RA patients, positive correlations were found between serum levels of 5-HT and the number of painful mandibular movements (r(s) = 0.36, n = 33, p = 0.042), as well as pain on maximum mouth opening (r(s) = 0.41, n = 24, p = 0.047) and tenderness to digital palpation (r(s) = 0.49, n = 33, p = 0.003). In the healthy individuals, there was a negative correlation between plasma level of 5-HT and the TMJ pressure pain threshold (r(s) = -0.47, n = 20, p = 0.037). CONCLUSION: Peripheral serotonergic pain mechanisms seem to be activated by blood 5-HT in patients with seropositive RA, in contrast to seronegative patients.     

Mechanisms of central sensitization, neuroimmunology & injury biomechanics in persistent pain: implications for musculoskeletal disorders.

This review will offer an overview of the mechanistic pathways of chronic pain associated with musculoskeletal disorders (MSDs). Traditional electrophysiological pain pathways of these injuries will be reviewed. In addition, recent research efforts in persistent pain have characterized a cascade of neuroimmunologic events in the central nervous system that manifests in pain behaviors and neurochemical nociceptive responses. Physiologic changes in the central nervous system will be covered as they pertain to the interplay of these two areas, and also as they focus on MSDs and injuries. One such injury leading to persistent pain is radiculopathy, which results from nerve root compression or impingement and leads to low back pain. This painful syndrome will be used as an example to provide a context for presenting immune mechanisms of chronic pain and their relationship to injury. Measures of injury biomechanics are presented in the context of the resulting pain responses, including behavioral sensitivity, local structural changes, and cellular and molecular changes in the CNS. Lastly, based on these findings and others, a discussion is provided highlighting areas of future work to help elucidate methods of injury diagnosis and development of therapeutic treatments.     

Empathy beyond the conceptual level: core nonspecific factors of psychotherapy

The human mind contains much more than concepts. By only taking into account the conceptual level, a cared-for person may feel utterly lonely and abandoned, not deeply in contact with the caregiver, not deeply understood for who he or she really is. A chronic pain patient, for instance, may react to a purely conceptual-level communication, with its lack of deeper contact, by an increasing sense of loneliness. This in itself may substantially contribute to the suffering of chronic functional pain or even functional disorders in general. In dealing with chronic pain patients, as with any patients, it is therefore very important to develop a sense of empathy that goes beyond this, towards deeply understanding the patient as complete person. This sheds a profound light on the all-important nonspecific factors of psychotherapy, which according to many researchers form the only profoundly active principle in psychotherapy.