Inflammatory stimuli initiate a cascade of events, including the production of tumor necrosis factor (TNF) α , ILs, chemokines, nerve growth factor (NGF), sympathetic amines, leukotrienes and PGs, with a complex impact on pain production. Cyto- kines induce hyperalgesia by a number of direct and indirect actions. Thus, IL1β activates nociceptors directly via intra- cellular kinase activation, but it may also cause indirect nociceptor sensitization via the production of kinins and prostanoids . TNF α also activates sensory neurones directly via the receptors TNFR1 and TNFR2 and initiates a cascade of inflammatory reactions through the production of IL1, IL6 and IL8 [66,67]. It is significant that direct TNF α application in the periphery induces neuropathic pain behavior that is blocked by ibuprofen and celecoxib , while nerve ligation causes increased TNF α in damaged as well as adjacent undamaged axons . Interestingly, anti-TNFα treatment with the TNF antibody adalimumab produced a prolonged reduction of pain symptoms in OA . These are encouraging preliminary data but will require further support. Chemokines are important peripheral and central regulators of chronic inflammation, typically orchestrating leucocyte migration. However, recent studies implicate chemokine receptors in brain development, neurodegenerative conditions and synapse activity. Receptors have been detected throughout the CNS in the macrophage-‘like’ microglial cells, astrocytes, oligodendrocytes and neurons . Receptors have been co-localized with isolectin B4 and substance P primary afferent neurons and dorsal root ganglion cultures respond to chemokines with transient Ca 2+ influx .
14 Read more
CiOA shares some features with human OA, such as the development of synovitis, cartilage erosion and osteophytes [8, 11], which we have shown to be GM- CSF dependent ; there are a number of studies using this macrophage-dependent model in rodents (see, for example [8–13, 37, 38]). Interestingly, the proportion of synovial macrophages was not altered in the absence of GM-CSF, although there was a reduction in the propor- tion of neutrophils. A lack of IRF4 resulted in a slight re- duction in early synovitis, with once again a reduction in the proportion of synovial neutrophils, while a lack of CCL17 had no effect; however, in the absence of either GM-CSF , IRF4 or CCL17 there was no pain develop- ment at week 3 and significantly reduced histologic scores and osteophyte size at week 6 (Fig. 1a-c). Thus, the degree of early synovitis observed upon deletion of IRF4 and CCL17, in contrast to that observed upon de- letion of GM-CSF, does not correlate with the
10 Read more
lived for intra-articular glucocorticoids. One study did not show a significant effect of intra-articular glucocorticoid (triamcinolone) treatment on knee pain, although there was greater cartilage volume loss after two years of triamcinolone treatment (40 mg/3 months) compared to placebo treatment; the usual short-term benefits of intra-articular glucocorticoid treatment were probably missed in this study 11 . Low dose (5 mg/day) oral glucocorticoids did not improve pain measured by visual analogue
27 Read more
At the time of writing, clinical development of tapentadol ER has been completed, submitted, and reviewed by the FDA. The submission included a number of large-scale, randomized, active comparator-controlled and placebo- controlled Phase III studies that evaluated the safety and efficacy of tapent- adol in patients with chronic osteoarthritis, low back pain, or pain associated with diabetic peripheral neuropathy. Tapentadol ER has also been evaluated in a 1-year, active- controlled, open-label Phase III safety trial. The FDA has not requested additional efficacy trials, but in a complete response letter provided on November 2010, the agency seeks additional information regarding modifications to the ER tablet that increase mechanical resistance to breaking or crushing prior to granting approval for use. In a series of large- scale, controlled clinical trials, tapentadol ER was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to severe chronic osteoarthritis pain and lower back pain. 1,2,4 Like the
As chronic pain interfered with daily functioning of obese individuals, it can have a negative effect on weight loss [5, 9]. There are several measurements used in past studies to assess body pain which include the Visual Analogue Scales (VAS), the Numeric Rating Scale for Pain (NRS Pain), the McGill Pain Questionnaire (MPQ), the Chronic Pain Grade Scale (CPGS), the Short-Form 36 Bodily Pain Scale (SF-36 BPS) and the Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) . These measurements were widely used in different settings to assess chronic pain related to specific diseases and the VAS is the most common method used in the clinical and the community settings. It is a practical and concise tool, which comes along with a helpful graphic diagram and is more suitable for various community groups. There is limited evidence on the utilisation of the VAS in a community-based weight loss intervention study in Malaysia. Therefore, the aim of this paper was
Several studies have assessed the tolerability of tapentadol and compared it to that of conventional opioid therapy. In a large, randomized open-label Phase III study of patients with chronic knee or hip osteoarthritis pain or low back pain, patients were randomized to receive twice-daily doses of tap- entadol ER (100–250 mg) or oxycodone HCl CR (20–50 mg) for up to 1 year. The incidences of several types of TAEAs were lower for the tapentadol group; these include constipa- tion (22.6% versus 38.6%), nausea (18.1% versus 33.2%), vomiting (7% versus 13.5%), and dizziness (14.8% versus 19.3%). Furthermore, TEAEs led to discontinuation less fre- quently in the tapentadol group than in the oxycodone group (22.1% versus 36.8%). In a recent analysis of three random- ized controlled trials, patients with hypertension who had been treated with tapentadol ER were found to have no clinically meaningful changes in blood pressure or heart rate. 83
11 Read more
tensile strain results in increased proteoglycan and aggrecan synthesis, needed to promote cartilage homeostasis. The strain applied to chondrocytes in this study was designed to mimic continuous passive motion, a technique often used in knee rehabilitation to reduce joint stiffness and inflammation. The results of this study may support the use of continuous passive motion as an effective means of inhibiting the inflam- matory process in an osteoarthritic knee joint. In addition, this may provide insight into the pathways by which repetitive exercises such as stationary cycling may provide pain relief, as was the case in the study by Salacinski and colleagues. 28
11 Read more
(TNF)- α , and prostaglandins, are all over-produced in chondrocytes harvested from patients with OA (as reviewed by Pelletier and coworkers ) and help to perpetuate the inflammatory process. NO has also long been considered to be a catabolic factor that contributes to the OA disease pathology by mediating a number of processes, including apoptosis, and perpetuating the expression of proinflam- matory cytokines . High concentrations of nitrites and nitrates have been found in the synovial fluid and plasma of patients with arthritis . Although increased levels of NO activity have been found in the synovial fluid of patients with rheumatoid arthritis [3,4] and juvenile idiopathic arthritis , analyses of the NO content in the synovial fluid of patients with OA have yielded contradictory findings [6,7]. NO concentrations are, however, significantly increased in the synovial fluid of a canine OA model . These findings, in combination with experiments described below, contribute to the prevailing hypothesis that NO is a proinflammatory and proapoptotic factor that, when present in excess, is detrimental to the joint and contributes to OA pathogenesis. Despite the evidence that NO is primarily a catabolic factor in OA, newer studies have suggested that this view of NO may be too simplistic. Instead, there is evidence that the effects of NO may be concentration and/or time dependent. In addition, studies suggest that NO and its reactive oxygen species (ROS) derivatives may also have opposing effects, both destructive and protective. Finally, there is a small but growing body of literature demonstrating that NO has beneficial effects on other cell types, including tendons and osteoblasts, which could also potentially be present in chondrocytes. In addition, NO and its derivatives also play critical roles in both the production and reduction of noci- ception and pain, which is the primary cause of functional
The primary outcome measure was change in reported pain between the groups over time. Pain was reported daily over the 3-week trial period using a paper-based 100 mm visual analog scale (VAS) without intervals. The VAS was a straight line with “no pain” at one end and “worst imaginable pain” at the other. A VAS was chosen because participants could accurately record their pain perceptions without limitation (eg, by a Likert system) and measurement differences of 1% may be captured. Participants were given the paper VASs and asked to complete one per day, at the same time each day.
because they live in rural areas and rely on family for transportation. As a consequence we completed the study with a small sample size. Therefore, some results were not adjusted for confounding variables and this is another limitation of our study as adjustment for these variables may cause your significant findings to become insignificant. However, as a pilot study where results are normally or only expected to be shown in descriptive way, we obtained important findings of significant impact and relevance to the clinical setting. Future studies should include a larger sample size with a longitudinal design. This type of study would provide additional information about long-term changes in pain and disability in individuals with knee OA. Further investigations should focus on treatment for depression and weight loss therapy and try determining whether a combination of treatments is more effective than treating obesity or depressive symptoms individually. Future research should also measure the impact of reduction in depressive symptoms and body weight on physical health and well-being of individuals with knee OA before and after total knee replacement surgery.
In engineering design there is the necessity to carry out biometry of an ailment on sufferers as a pedestal for development of a device that manages the ailment. In this paper, we have carried out the biometry of pain in patients of knee osteoarthritis (OA). The study evaluates causes of knee pain, its severity and effects on daily activities, psychosocial life and sleep. The study population was drawn from five government hospitals in Lagos State. After initial treatment, only patients with knee pain were enlisted as subjects in the study. A standardized questionnaire was used for data collection to determine the causes of the pain, its severity and effects on the operational performance of individuals with OA. Chi-square analysis was carried out on our samples at a statistical level of significance of α = 0.05. Out of 525 questionnaires that were distributed, 431 (82.10%) were responded to. The outcomes of this study indicate that OA affects individuals of all ages and genders irrespective of their topographical locations. 242 (89.67%) women and 189 (88.97%) men were affected with higher incidence recorded within the age groups of (41-50) and (61-70) with frequency values of 62 (84.00%) and 85 (92.85%) respectively. The risk factors include overweight, occupational hazard and previous history of knee injury. Overweight 132 (91.86%), Obesity 59 (92.28%) and Extreme Obesity 5 (90.37%). Previous injury 173 (90.52) % and non-previous injury is 258 (87.78%). This work studies biometrics of OA as basis for developing a therapeutic management of knee OA, and this is to improve the patient’s pain tolerance and relief of swollen knee without adverse effect.
J.H. Abbott et al., (2013) conducted a study to evaluate the clinical effectiveness of manual physiotherapy and exercise physiotherapy in addition to usual care for patients with osteoarthritis of the knee. Design In this 2 × 2 factorial randomized controlled trial, 206 adults who met the criteria were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index after 1 year. The study concluded that Manual physiotherapy provided benefits over usual cares that were sustained to 1 year.
82 Read more
In the present study, patients entered the study with an average BS-11 pain score of 6.2. After initiation of TDB, the mean BS-11 score decreased by 2.3 unit one week after the end of the titration period and the reduction was maintained till the end of the treatment period (LS mean change: −2.5 at visit 6). A reduction of approximately 2 units from baseline on the 11-point numeric rating scale has been demonstrated to correspond to a clinically mean- ingful improvement . The improvements in BS-11 score observed in this study are therefore considered clinically relevant. In addition, the majority of patients did not require additional rescue medications for pain. Similar improvements were observed in an open-label, random- ized trial conducted in UK . In this trial, reduction in BS-11 score was sustained over the 11-week treatment period (mean reduction: 3.6 at end of titration and 4.0 at week 12) in patients with knee and/or hip osteoarthritis who received TDB plus oral paracetamol . The ben- efits of TDB in providing analgesia in patients with chronic moderate to severe non-malignant pain are supported by results from other studies [25, 26]. In a prospective study of younger patients and elderly patients with osteoarthritis-related pain in Sweden, Karlsson et al. observed significant reductions in BS-11 score in patients who were treated with TDB, regardless of age (LS mean change: −1.9 to −2.2). In addition, patients used less res- cue medications after the start of the 12-week treatment. The mean number of tablets of rescue medication taken each day reduced from 5.2 to 5.7 at baseline to 2.1 to 2.8 during the treatment period . In another open-label, randomized study comparing the efficacy and safety of TDB with prolonged-release tramadol tablets, similar improvement in BS-11 score (LS mean change: −2.3) was reported in Swedish patients after 12 weeks of treatment with TDB .
12 Read more
professionals can do better and quickly in line with NICE guidance. All practitioners who treat musculoskeletal problems should provide their patients with hardcopy or electronic exercise sheets and provide directions to appropriate web information on the nature and treatment of osteoarthritis. We must rebuff the view that joint pain is an inevitable part of ageing. We must promote muscle strengthening as a critical component of osteoarthritis care, no matter the age of the patient, and we must support our patients with guided activity plans to reduce the burden of joint pain.
Osteoarthritis (OA) is a progressive and degenerative dis- ease of the articular joints involving the articular cartilage, synovium, and subchondral bone, and is a leading cause of pain and disability in the adult population . Despite the high prevalence of OA, there is currently no cure or effect- ive treatment that halts or reverses disease progression . While current pharmacologic treatments such as analge- sics and nonsteroidal anti-inflammatory drugs (NSAIDs) provide symptomatic relief, such as relieving pain, they do not exert a clear clinical effect on OA disease prevention or modification . In most cases, long-term use of these treatments has been associated with substantial gastro- intestinal, renal, and cardiovascular side effects . There is a clear and urgent need for new therapeutic strategies that are effective and safe for OA treatment.
12 Read more
There was another clinical trial as well, which evaluated the efficacy, tolerability, and safety of orally administered tapen- tadol ER. Tapentadol at doses of 100 mg to 250 mg BID was compared with placebo in patients with moderate to severe pain due to chronic, painful DPN who tolerated tapentadol ER after having had an initial treatment. During initial treat- ment, these patients with DPN had pain improvement after a 3-week, open-label titration period (ClinicalTrials.gov identifier: NCT01041859). This second study was successful in showing the efficacy, safety, and tolerability of tapentadol ER in the treatment of chronic painful DPN. This has led to additional FDA approval for the treatment of neuropathic pain associated with DPN in April 2012. As of this writing, it is the only opioid with such an indication.
In this study, we have investigated the regulation of ECs and MMPs expression during OA development. Both ECs and MMPs are considered promising targets for the pharmaco- logical treatment of OA symptoms, including OA-related pain. The intra-articular injection of MIA produces weight- bearing asymmetry, which is considered as an indication of nociceptive pain similar to this observed in OA patients. We reported that the progress of weight-bearing asymmetry is biphasic, possibly reflecting the initial, inflammation-driven phase of pain followed by the second, chronic phase that is connected to pathomorphological alterations within the joint. The observed two-stage progression of the disease is consistent with our previous results and with other reports showing biphasic pain profile following injection of 3 mg of MIA in rats. 16,38 Importantly, the altered weight distribution is
17 Read more
recurrent joint pain for at least a year prior to treatment, and daily pain in the knee $30 mm, as assessed by a 1–100 mm Visual Analog Scale (VAS). The exclusion criteria were: unilateral knee OA, intra-articular administration of drugs to the affected knees within 6 months before the study, sys- temic corticosteroid therapy or physiotherapy (iontophoresis with anti-inflammatory drugs, soft [not heating] laser, and ultrasound therapy) in the previous 6 weeks, and knee pain due to malignant, autoimmune and inflammatory pathologies or resulting from defective pathologies of the knee.
Like other forms of chronic pain, the pain in RA is multifactorial and treatment options can vary. Cognitive behavioral therapy (CBT) has been studied in patients with chronic pain conditions, chronic low back pain, osteoarthritis, fibromyalgia, as well as in different psychi- atric disorders including depression, PTSD, and general- ized anxiety disorder . It is also first-line treatment for chronic insomnia . CBT focuses on identifying and changing behaviors and thoughts that are maladap- tive while helping patients develop coping strategies. It may help to ameliorate pain and disability by changing attitudes towards the illness. In a study looking at pa- tients with recent onset (< 2 years) of seropositive RA, those that receive CBT had a reduction in depressive symptoms and c-reactive protein as well as an improve- ment in joint involvement compared to those who did not receive CBT . Other studies have shown that CBT can reduce disability, depression/anxiety, and pain- related fear but do not decrease pain intensity . Interestingly, CBT may also change brain function and neuronal connection as magnetic resonance imaging done after treatment with CBT show increase activation in the prefrontal cortex, an area of the brain that is involved in regulating emotions to painful stimuli .
A high body mass index is a well-known risk factor for knee OA, and to a lesser degree for hip OA and hand OA, and probably acts through a change in load distribution in the knee , and systemic and local inflammatory cytokines [73,74] released by the adipose tissue. It also seems, however, to influence severity of symptoms; over- weight people more often experience morning stiffness in the knee and have more severe knee pain than those who are not overweight but with the same degree of radio- graphic severity . Although weight loss is a main goal in overweight OA patients, their weight might also have implications for other OA treatments.