Pain Control In Osteoarthritis Research Articles

Xibining inhibition of the PI3K-AKT pathway reduces M1 macrophage polarization to ameliorate KOA synovial inflammation and nociceptive sensitization

BackgroundPain is the most critical symptom of knee osteoarthritis(KOA), which seriously affects the quality of life of patients. Xibining (XBN), a traditional herbal compound, has achieved good results in the clinical treatment of KOA, and its mechanism of action is worth exploring in depth. ObjectiveIn vivo and in vitro models of KOA were constructed, and the potential drug action mechanism of XBN in improving osteoarthritis pain was explored in combination with transcriptomics. MethodsIn vitro experiments were also conducted to explore the effects of different treatments of BMDMs on TRP channels in DRG neurons by constructing a coculture system of BMDMs and DRG neurons. The specific mechanism by which XBN affects BMDMs was explored via participatory transcriptomics. ResultsOur results showed that KOA aggravated macrophage infiltration in synovial tissues and DRG tissues and increased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8 in synovial tissues and DRG tissues; XBN treatment improved inflammation in synovial tissues and macrophage infiltration in DRG tissues, and it decreased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8, consistent with the results of behavioral tests to improve nociceptive sensitization induced by KOA. The results from in vitro experiments showed that promoting macrophage M1-type polarization exacerbated TRP channel activation in DRG neurons and that XBN acted by inhibiting macrophage M1-type polarization. A reference transcriptome study showed that XBN may play a role in inhibiting M1 macrophage-type polarization in KOA by suppressing the PI3K-AKT pathway in BMDMs. We verified the conclusions obtained from transcriptomics via in vitro experiments. We place greater emphasis on the role that the intrinsic immune system plays in the area of pain control in osteoarthritis. ConclusionXBN improve KOA nociceptive sensitization by modulating the PI3K/Akt signaling pathway, attenuating the level of synovial inflammation and inhibiting M1-type macrophage polarization in synovial and DRG tissues in KOA mice.

A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients

BackgroundParacetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease.MethodsEight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm.The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system.ResultsAverage NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521).ConclusionsRemoving small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out.Trial registration numberNCT02691754 (Approved February 24, 2016).

Anti-inflamatórios não esteróides tópicos no tratamento da dor por osteoartrose do joelho – Uma revisão baseada na evidência

Aim: Osteoarthritis (OA) is a common form of degenerative joint disease with increasing prevalence. The knee is the most frequently affected joint and pain is an incapacitating symptom. The first line of treatment includes oral analgesics like acetaminophen and oral non-steroidal anti-inflammatory drugs (NSAID). However, the latter are associated with potentially severe side effects, making topical NSAID a possible, safer alternative. The aim of this review is to examine the evidence for the efficacy and safety of topical NSAID in the management of OA of the knee. Data sources: The National Guideline Clearinghouse, TRIP, The Cochrane Library, DARE, Bandolier, MEDLINE and other sites of international scientific associations were searched. Review methods: Databases were searched for guidelines and publications appearing between January and December 2012, in Portuguese, English or Spanish, using the search terms (“Administration, Topical” OR “Administration, Cutaneous”) AND (“Anti-Inflammatory Agents, Non-Steroidal”) AND “Osteoarthritis”. To evaluate the level of evidence and the strength of recommendations, the Strength of Recommendation Taxonomy (SORT) of the American Academy of Family Physicians was used. Results: We found 96 articles, of which 8 fulfilled the inclusion criteria. There were 4 guidelines and 4 meta-analyses selected for inclusion in this review. These studies show the short-term benefits for pain relief in OA of the knee with the use of topical NSAID. They demonstrate its tolerability and safety profile with few adverse effects. Conclusions: The available evidence from Randomized Controlled Trials of up to 12 weeks duration supports the efficacy of topical NSAID for pain control in OA of the knee (SORT B). Studies differed in the drugs investigated, as well as in the duration of treatment. This heterogeneity limits the conclusions that can be drawn and the generalizability of results. Studies with a longer period of follow-up are required.

A discrete-choice experiment of United Kingdom patients' willingness to risk adverse events for improved function and pain control in osteoarthritis

To assess patient preferences for treatment-related benefits and risks associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA). Using a chronic-illness panel in the United Kingdom, patients 45 years or older with a self-reported diagnosis of OA were eligible to participate in the study. Patient preferences were assessed using a discrete-choice experiment that compared hypothetical treatment profiles of benefits and risks consistent with NSAID use. Benefit outcomes (ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) were presented on a 0-to-100 mm scale. Risk outcomes (bleeding ulcer, stroke, and myocardial infarction [MI]) were expressed as probabilities over a fixed time period. Each patient answered 10 choice tasks comparing different treatment profiles. Preference weights were estimated using a random-parameters logit model. Final sample included 294 patients. Patients ranked reductions in ambulatory pain and difficulty doing daily activities (both: 6.32; 95% confidence interval [CI]: 5.0-7.6) as the most important benefit outcomes, followed by reductions in resting pain (2.80; 95% CI: 1.8-3.8) and stiffness (2.65; 95% CI: 0.9-4.4). Incremental changes (3%) in the risk of MI or stroke were assessed as the most important risk outcomes (10.00; 95% CI: 8.2-11.8; and 8.90; 95% CI: 7.3-10.5, respectively). Patients ranked ambulatory pain as a more important benefit than resting pain; likely due to its impact on ability to do daily activities. For a 25-mm reduction, patients were willing to accept four times the risk of MI in ambulatory pain vs resting pain.

A randomized, double-blind, multicenter trial of nimesulide-beta-cyclodextrin versus naproxen in patients with osteoarthritis

Background: Nonsteroidal anti-inflammatory drugs are the most widely used agents in the symptomatic treatment of osteoarthritis (OA). No data are presently available on the medium-term management of this disease with an on-demand treatment regimen, which nevertheless reflects medical practice. Objectives: The aim of this study was to compare nimesulide-beta-cyclodextrin and naproxen in terms of short-term (2 weeks) pain control with scheduled dosing and medium-term (5.5 months) pain control with on-demand dosing in patients with OA. Methods: In this multicenter, randomized, double-blind, controlled study, we compared 2 weeks of scheduled treatment plus 5.5 months of on-demand treatment in patients with OA of the hip and/or knee and moderate to severe pain, with no important concomitant disorders. Treatment consisted of nimesulide-beta-cyclodextrin (400 mg BID, orally = 100 mg nimesulide BID) or naproxen (500 mg BID). The primary outcome measures for scheduled dosing were pain on movement (measured by visual analog scale), morning stiffness score, Lequesne index, and adverse events. For on-demand dosing, the measures were the same as for scheduled dosing, plus duration of treatment and global assessment of efficacy and tolerability by patient and physician. Results: After 2 weeks, there was equivalent reduction from baseline in pain on movement in the 2 treatment groups (nimesulide-beta-cyclodextrin, −41.5%; naproxen, −40.5%); the reduction was significant after 1 week ( P < 0.001). The findings were also similar for the morning stiffness score and Lequesne index. There were no significant differences in mean duration of on-demand treatment (nimesulide-beta-cyclodextrin, 163.03 days; naproxen, 166.3 days) or in mean consumption of study drug (nimesulide-beta-cyclodextrin, 0.85 ± 0.61 sachets/d; naproxen, 0.74 ± 0.42 sachets/d). Withdrawal due to intolerance occurred in 8 patients given nimesulide-beta-cyclodextrin and 13 patients given naproxen, with no significant difference between groups; 3 and 12 patients, respectively, withdrew due to gastrointestinal intolerance, a finding that was significantly different between groups ( P < 0.01). Global assessment of efficacy by patient and physician was similar for both drugs. Assessment of tolerability significantly favored nimesulide-beta-cyclodextrin on the physician assessments ( P < 0.05) but was similar for the 2 drugs on the patient assessments (physicians, 46.9% vs 30.9%; patients, 43.5% vs 33.3%). Conclusions: The results suggest that nimesulide-beta-cyclodextrin provides similar pain relief to naproxen in the management of OA of the hip and/or knee and is associated with fewer gastrointestinal adverse reactions. On-demand dosing may be an effective and well-tolerated low-dose regimen of nonsteroidal anti-inflammatory drugs for the maintenance of pain control in OA in the medium term.

Evaluation of pain control in osteoarthritis in the elderly using tramadol hydrochloride

Evaluation of pain control in osteoarthritis in the elderly using tramadol hydrochloride

Randomized Trial of Codetron for pain Control in Osteoarthritis of the Hip/Knee

Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial, saphenous, popliteal and sciatic nerves, and tender points. Seventy-four percent of patients in the real Codetron (Group A) and 28% of the patients in sham Codetron (Group B) improved their pain level more than 25% as measured by visual analogue scale. The difference in pain improvement in the two groups was statistically significant (p less than 0.02 using Fisher's exact probability ratio). Other functional parameters proved to be insensitive to change in this study. This is highly suggestive of beneficial effect of nonhabituating Codetron as a complementary modality in the therapy of chronic pain conditions such as osteoarthritis.