Treatment Of Osteoarthritis Pain Research Articles

An update on targets for treating osteoarthritis pain: NGF and TRPV1.

a)Osteoarthritis (OA) is the most common form of arthritis, and pain is the primary symptom of the disease, yet analgesic options for treating OA pain remain limited. In this review, we aimed to give an update on the current clinical and preclinical studies targeting two pathways that are being investigated for treating OA pain: the nerve growth factor (NGF) pathway and the transient receptor potential vanilloid-1 (TRPV1) pathway. b)Antibodies against NGF, small molecule inhibitors of TrkA, TRPV1 agonists, and TRPV1 antagonists are all in different stages of clinical and pre-clinical testing for the treatment of OA pain. NGF antibodies have shown efficacy in the primary endpoints tested compared to placebo, however, rapidly progressive OA has been consistently observed in a subset of patients and the cause remains unclear. TRPV1 agonists have also demonstrated reduced pain with no serious adverse events - the most common adverse events include a burning or warming sensation upon administration. c)Targeting the NGF and TRPV1 pathways appear effective for reducing OA pain, but further work is needed to better understand which patients may benefit most from these treatments. The anti-NGF antibody tanezumab and the TRPV1 agonist CNTX-4975 have both received fast-track designation from the FDA for the treatment of OA pain.

Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain.

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.

The benefit of Curcuma longa and Boswellia serrata to improve quality of life in osteoarthritis patients: a randomized controlled trial

<p class="abstract"><strong>Background:</strong> Quality of life (QoL) can be affected by chronic pain in osteoarthritis (OA). Previous studies showed that combination of <em>Curcuma longa</em> (CL) and <em>Boswellia serrata</em> (BS) extract (CB extract) are promising for alternative treatment for pain in OA. This study aimed to measure the benefit of CB extract to improve QoL in patients with OA.</p><p class="abstract"><strong>Methods:</strong> This was a randomized controlled trial (RCT) in OA patients. Subjects were randomized to 3 different group (Group 1: CB extract (350 mg of CL and 150 mg BS) and NSAID (400 mg ibuprofen or 50 mg diclofenac sodium); group 2: CB extract; group 3: NSAID). Each medication was taken two times per day for 4 weeks. QoL measured using 5Q-5D-5L that include five dimensiones in 5Q-5D: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, with 5 levels of severity.<strong></strong></p><p class="abstract"><strong>Results:</strong> There were 105 subjects at baseline. After 4 weeks of study, remained 95 subjects. The most common problem in group 1, 2, and 3 was pain (n=23, n=8, n=15 respectively). The improvement of level of severity in group 1 after 4 weeks of treatment was significant in mobility problems (p=0.002), pain/discomfort (p<0.001), and anxiety/depression (p=0.008). A significant improvement was only seen in usual activity problems (p=0.013) in group 2. The decrease of level of severity in usual activity problems (p=0.034), pain/discomfort (p=0.005), and anxiety/depression (p=0.018) in group 3 were also statistically significant.</p><p class="abstract"><strong>Conclusions:</strong> CB extract was beneficial to improve QoL in OA patients with a less side effect compared to NSAID.</p>

Pain inhibitory mechanisms and response to weak analgesics in patients with knee osteoarthritis.

Conditioned pain modulation (CPM) and offset analgesia are different features of descending pain inhibition. This study investigated CPM, offset analgesia and clinical pain measures in patients with knee osteoarthritis (KOA) before and after treatment with the combination of a non-steroidal anti-inflammatory drug (NSAIDs) plus acetaminophen. Forty-two patients with KOA received Ibuprofen 1.2g/daily and acetaminophen 3.0g/daily for three weeks. Before administration, CPM magnitude was assessed as the difference between cuff pain detection (cPDT) with and without a conditioning stimulus (evoked by tourniquet pain). Offset analgesia was assessed as the pain intensities evoked by a constant 46°C for 30-s stimulus compared to an offset analgesia paradigm of 46°C for 5-s, 47°C for 5-s and 46°C for 20-s. The worst pain within the last 24-hr and pain during activity were assessed before and after treatment. Clinical pain significantly decreased after treatment (p<0.001) and less efficient CPM before treatment was associated with weaker analgesic effect (R=0.354, p=0.043). No significant modulation of CPM or offset analgesia was found for the treatment. This study found that less efficient CPM is associated with reduced analgesic effect of NSAIDs plus acetaminophen in patients with KOA whereas the treatment did not modulate CPM nor offset analgesia magnitude. This study demonstrated that conditioned pain modulation is correlated with the response to a standard pharmaceutical interventions treating osteoarthritis pain. Furthermore, we demonstrated that a decrease in clinical pain intensity is not associated with a normalization of conditioned pain modulation or offset analgesia, which questions if restoring these descending pain inhibitory mechanisms are pain intensity driven.

Evidence-Based Recommendations on the Pharmacological Management of Osteoarthritis and Chronic Low Back Pain: An Asian Consensus

The overall burden of chronic musculoskeletal pain in Asian countries will continue to increase as the population ages, as will the demand for safe and effective pain management. Currently available Asian guidelines are mostly outdated and targeted only to primary care. Implementation of international guidelines may be unsuitable for Asian patients due to cultural, local economic and regulatory factors. With the aim of developing Asian-specifi c consensus recommendations for the pharmacological management of osteoarthritis (OA) pain and chronic low back pain (cLBP), we convened to review and discuss recent available evidence for pharmacotherapy, clinical experiences, and current practice challenges they face in the region, including challenges in opioid use. Taking these into consideration, we provided general recommendations for the overall assessment and management of OA pain and cLBP. The strength of the recommendations regarding the use of pharmacological agents was assessed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Where evidence is confl icting or limited, we made no recommendation pending the availability of further evidence. We recommend topical non-steroidal anti-infl ammatory drugs (NSAIDs) as a fi rst-line pharmacological treatment of OA pain, while oral NSAIDs should be considered as a fi rst-line pharmacological treatment of cLBP. Acetaminophen has been commonly used as the fi rst-line treatment for OA pain and cLBP, but its long-term use is not recommended based on recent evidence. These consensus recommendations are not prescriptive, and serve as a guide for decision-making in clinical practice. The optimal management of OA pain and cLBP should ultimately be individualized to each patient.

The Comparison of Two Crosslinked Hyaluronate for the Treatment of Osteoarthritis Pain

The Comparison of Two Crosslinked Hyaluronate for the Treatment of Osteoarthritis Pain

STUDY ON BOTANICAL CHARACTERISTICS AND ACETYLCHOLINESTERASE INHIBITORY ACTIVITY OF TWO SPECIES LEEA SP. - LEEACEAE

Background: The species belonging to the genus Leea, Leeaceae are reported to have anti-inflammatory, antioxidant, analgesic, antibacterial effects, and have been used to treat osteoarthritis pain, rheumatism, digestive and cancer diseases. The project aims to study botanical characteristics and Acetylcholinesterase inhibitory activity of two species of genus Leea. Materials and method: Two species Leea rubra Blume ex Spreng. and Leea curtisii King., Leeaceae were identified the powder characteristics, microsurgical characteristics by double dyeing method, determined Acetylcholinesterase inhibitory activity by the method of Ellman. Results: Identified characteristics of microsurgery and powder of 2 studied species; total extracts and fractional extracts of 2 studied species shown the average Acetylcholinesterase inhibitory activities with the IC50 values in the range of 42.44 to 97.96 µg/ml. Conclusion: The project contributed to standardize microbiological characteristics and determined Acetylcholinesterase inhibitory activity of two species belonging to the genus Leea. Key words: Acetylcholinesterase, Leea rubra, Leea curtisii, microsurgery, powder characteristics

Tactics of Safe Management of Comorbid Patients with Osteoarthritis in the Practice of a Family Doctor: What is the Choice?

The problem of comorbidity is recognized as one of the key in modern world medicine, it requires consideration of all interacting factors and risks and coordinated therapy. From a complex of comorbid processes, it is necessary to distinguish clusters of diseases, most often combined with each other or accompanying other diseases, including the musculoskeletal system, widespread, occurring in all age groups of the population and being the leading cause of chronic disability and a significant reduction in the quality of life of patients. Traditional treatment of pain in osteoarthritis is the appointment of a special group of drugs - non-steroidal anti-inflammatory drugs, which have a pronounced positive therapeutic effect, but have a fairly large range of adverse events. In addition, in accordance with modern guidelines for the treatment of OA, among the pharmacological methods, the leading place is occupied by delayed-acting drugs (S YSADOA), including the original biotechnological drug Alflutop.The results of many studies show that Alflutop has an acceptable profile of both gastrointestinal and cardiovascular safety and proven clinical efficacy, which allows it to be chosen for the treatment of patients with various comorbid pathology, which is characteristic of elderly people in particular.

Pharmacological Treatment of Pain in Osteoarthritis: A Descriptive Review.

Osteoarthritis (OA) is the most common form of arthritis that is characterized by loss of articular cartilage and new formation of bone. Pain and functional disability are common features that lead to disability and poor quality of life. This review discusses the current state of knowledge concerning the treatment of pain in OA, with a focus on pharmacological treatments. This includes the use of non-steroidal anti-inflammatory drugs, acetaminophen, and other disease-modifying agents. An updated review of the role of anti-nerve growth factor monoclonal antibodies and other novel agents in the treatment of OA is also presented. In addition, a discussion of current research on biological agents such as small molecules targeting ion channels and G protein-coupled receptors is included. These new pharmacological interventions expand the frontier for treatment of patients with OA. The purpose of the review is to provide clinicians with information about the effectiveness of different pharmacological modalities in order to enable them to make the best choices for the treatment of their patients.

THE NEUROPATHIC COMPONENT OF PAIN SYNDROME IN OSTEOARTHRITIS

Objective: to access (according to data of literature references) mechanisms of development of neuropathic pain in osteoarthritis and methods of its management. Material and methods. Analysis of publications containing information on neuropathic pain in osteoarthritis which are stored on the PubMed resource and the Russian information portal eLIBRARU.RU. Results. The pathogenesis of neuropathic pain of various localization in osteoarthritis has been determined, methods of its treatment have been studied. Conclusion. The work draws an inference that it is requisite to develop a more thorough approach to the treatment of pain in osteoarthritis and assessment of its effectiveness and safety.

Efficacy of commonly prescribed analgesics in the management of osteoarthritis: a systematic review and meta-analysis.

Pain management is a cornerstone of osteoarthritis (OA) management. The aim of this review is to obtain current, literature-based estimates of the effect of common pharmacologic treatments on pain reduction in OA. A MEDLINE search (2006-2016) was conducted for randomized controlled trials studying acetaminophen, oral NSAIDs, topical NSAIDs, COX-2 inhibitors, and opioids in the treatment of OA pain. Drug effect on pain was estimated using relative change in pain, and expressed as percentage change. An overall effect for each drug category was obtained as a weighted average of study-specific effects, with weights based on each study's sample size. Twenty-nine studies were included. The effect on pain was estimated in a total of 43 treatment arms (acetaminophen n = 6, oral NSAIDs n = 9, topical NSAIDs n = 8, COX-2 inhibitors n = 9, and opioids n = 11). Relative (%) changes in pain were found to be as follows: acetaminophen = 32.5, oral NSAIDs = 34.3, topical NSAIDs = 40.9, COX-2 inhibitors = 36.9, and opioids = 35.4. The effects of 5 major drug categories in the treatment of OA pain were reviewed with data extracted from 29 studies published from 2006 to 2016. Acetaminophen was found to have an RC value close to that of oral NSAIDs. The effects of oral NSAIDs, COX-2 inhibitors, and opioids in controlling pain were similar to what has been demonstrated in previous literature. Topical NSAIDs were found to have a greater RC than oral NSAIDs.

Pharmacological effects of N-[2-[[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]ethyl]hyaluronamide (diclofenac Etalhyaluronate, SI-613), a novel sodium hyaluronate derivative chemically linked with diclofenac

BackgroundOsteoarthritis (OA) is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have investigated the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), which is a potentially safer and more effective treatment for OA knee pain. In this study, we evaluated the pharmacological effects of SI-613 in experimental arthritis models.MethodsWe compared the analgesic and anti-inflammatory effects of intra-articularly administered SI-613, hyaluronic acid (HA), and of orally administered diclofenac sodium (DF-Na) in rat silver nitrate-induced arthritis model and rabbit antigen-induced arthritis model.ResultsA single intra-articular (IA) administration of SI-613 significantly suppressed pain responses in rats in a dose-dependent manner. The analgesic effects were greater than those of HA, a mixture of DF-Na and HA, or an oral once-daily administration of DF-Na. In the rabbit arthritis model, SI-613 significantly reduced knee joint swelling compared with that in the control group on day 1 after a single IA injection. This significant anti-inflammatory effect was observed until day 28. In the pharmacokinetic study, the DF concentration in the synovium after SI-613 administration reached its maximum concentration of 311.6 ng/g on day 1, and gradually declined to 10 ng/g by day 28. It fell below the lower limit of quantification on day 35. Thus, a clear correlation was found between pharmacokinetics and pharmacodynamics. These results demonstrate that SI-613 exerts its long-lasting and potent anti-inflammatory effect by sustainable release of DF in the knee joint tissues.ConclusionA single IA injection of SI-613 was shown to exert analgesic and anti-inflammatory effects for 28 days in non-clinical pharmacological studies, suggesting that SI-613 will be a promising candidate in the treatment of osteoarthritis pain.

Pharmacological treatment of osteoarthritis-related pain

Joint pain due to osteoarthritis (OA) is often severe and disabling and affects alarge proportion of the aging population impairing daily living and quality of life. Numerous pharmacological treatment approaches are available. Including major OA guidelines this review presents the current evidence of pharmacological therapies in OA-related pain and covers topical, oral and intraarticular treatment approaches. In patients with mild OA topical nonsteroidal antiinflammatory drugs (NSAIDs) can be recommended. Topical capsaicin can be used when other treatments are ineffective or contraindicated. In patients with moderate to severe OA oral NSAIDs are suggested at the lowest effective dose for the shortest possible duration to control symptoms. Importantly, drug-related side effects and gastrointestinal, cardiovascular and renal comorbidities need to be taken into account. In patients with multiple-joint OA and high risk of NSAID-induced adverse events duloxetine can be considered. The evidence of metamizole, symptomatic slow-acting drugs in osteoarthritis and other nutritional supplements in the treatment of OA pain is uncertain and the use of opioids is not routinely recommended. In patients suffering from severe OA-related pain intraarticular injections with glucocorticoids can be suggested to achieve short-term pain relief. Evidence for interventional approaches using hyaluronic acid or platelet-rich plasma is uncertain. Yet, the efficacy of pharmacological therapies in OA-related pain is often inconsistent and severe adverse events might occur. Thus, critical use of the different treatment options considering patient-related comorbidities and nonpharmacological therapies is of major importance.

Biomechanical Response to Osteoarthritis Pain Treatment May Impair Long-Term Efficacy.

Pain has an important physiologic role and acts with or stimulates motor system adaptations to protect tissue from threats of damage. Although clinically beneficial, removing the protective pain response may have negative consequence in osteoarthritis, a mechanically mediated disease. We hypothesize motor system adaptations to joint pain and its treatment may impact osteoarthritis progression, thereby limiting efficacy of pain therapies.

Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice

BackgroundNerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice.MethodSix-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4–L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted.ResultsOn gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p < 0.05).ConclusionsMIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee.

Mechanosensitive ion channels in articular nociceptors drivemechanical allodynia in osteoarthritis.

Osteoarthritis (OA) is a disabling and highly prevalent condition affecting millions worldwide. Pain is the major complaint of OA patients and is presently inadequately managed. It manifests as mechanical allodynia, a painful response to innocuous stimuli such as joint movement. Allodynia is due in part to the sensitization of articular nociceptors to mechanical stimuli. These nociceptors respond to noxious mechanical stimuli applied to their terminals via the expression of depolarizing high-threshold mechanosensitive ion channels (MSICs) that convert painful mechanical forces into electrical signals. In this study, we examined the contribution of MSICs to mechanical allodynia in a mouse model of OA. Sodium mono-iodoacetate (MIA) was injected in the left knee of adult male Trpv1:Cre; GFP mice. Primary mechanical allodynia was monitored using the knee-bend test. Single-channel patch clamp electrophysiology was performed on visually-identified knee-innervating nociceptors. Dorsal horn neuronal activation was assessed by Fos immunoreactivity. In examining the gating properties of MSICs of naïve and OA mice, we discovered that their activation threshold is greatly reduced, causing their opening at significantly lower stimuli intensities. Consequently, nociceptors are activated by mild mechanical stimuli. These channels are reversibly inhibited by the selective MSIC inhibitor GsMTx4, and the intra-articular injection of this peptide significantly reduced the activation of dorsal horn nociceptive circuits and primary mechanical allodynia in OA mice. These results suggest that MSICs are sensitized during OA and directly contribute to mechanical allodynia. They therefore represent potential therapeutic targets in the treatment of OA pain.

Osteoarthritis: Nerve ablation - a new treatment for OA pain?

Pain in osteoarthritis (OA) can be resistant to the medical and surgical treatments currently in use. Local denervation of the arthritic joint could offer a new approach to relieve OA pain, if the results of a new cryoneurolysis clinical trial are confirmed.

Intraarticular Pulsed Radiofrequency vs. Radiofrequency Neurotomy in Patients with Chronic Knee Pain due to Osteoarthritis (OA)

Background: Advanced age usually suffer from painful osteoarthritis of knee (OA). Treatment of OA pain by nonsteroidal anti-inflammatory is of restricted benefit and surgery is challenging in many patients due to associated medical problems. In this study we used either intraarticular PRF or radiofrequency neurotomy to control pain in patients with chronic knee pain. Aim: The primary outcome of the study was the pain score 10 cm Visual Analog Scale (VAS). The secondary outcome of the study was (1) WOMAC scores (2) Amount of analgesic medications. Methods: This study was conducted on 100 adult patients more than 60 years with chronic knee pain (grade 3 or grade 4) osteoarthritis. Patients were divided into two groups each group contain 50 patients. In group I (intraarticular PRF), patients were treated with PRF where patient was placed in a supine position on the fluoroscopy table, knee joint was flexed to 15°, No genicular block tests were performed. Group 2 (radiofrequency neurotomy), patients were treated with radiofrequency neurotomy. Where patients were placed in a supine position on the fluoroscopy table, knee joint was flexed to 15° and genicular block tests were performed. Results: Our results showed that both groups were comparable regarding age, sex, weight and height. A significantly improvement of pain was noticed in group II when compared to group I at 1 week, 1 month, 3 months and 6 months, 9 months and 12 months (3.2 ± 1.9, 1.8 ± 0.4, 1.9 ± 0.5, 2.1 ± 0.8, 2.2 ± 0.5, 2.9 ± 0.6) p<0.001. In Group 1, there was a significant decrease in mean of VAS scores in comparison to the pre-study values at 1 week, 1 month, 3 months and 6 months (5.6 ± 0.8, 3.8 ± 1.7, 3.9 ± 1.9, 4.2 ± 1.6). While in Group 2 the significant decrease present at 1 week, 1 month, 3 months and 6 months, 9 months and 12 months compared with pretreatment values was (3.2 ± 1.9, 1.8 ± 0.4, 1.9 ± 0.5, 2.1 ± 0.8, 2.2 ± 0.5, 2.9 ± 0.6). Conclusion: Both, the radiofrequency neurotomy or pulsed radiofrequency controls pain in patients with chronic knee pain, decreases amount of analgesic medications consumption, minimize post-operative complications with the upper hand to radiofrequency neurotomy.

Effects of deep heating to treat osteoarthritis pain: systematic review

ABSTRACT BACKGROUND AND OBJECTIVES: Osteoarthritis is an inflammatory and degenerative joint disease, causing pain, musculoskeletal disorders and impact on functionality, daily life activities and quality of life. The action of physical agents by means of deep heating seems to be an alternative to treat such disease. This study aimed at verifying the effects of deep heating on osteoarthritis patients. CONTENTS: A systematic review was carried out in Medline, Scielo and LILACS databases as from keywords Osteoarthritis, Induced Hyperthermia, Physiotherapy and Ultrasound, and other keywords such as Deep heat, Microwaves and Short-waves, in Portuguese, English and Spanish, in the period from January 2005 to January 2016, and 986 articles were found. Initially, 16 potentially relevant articles were selected for the study and, after a judicious qualitative analysis, nine complete articles meeting inclusion criteria were selected. CONCLUSION: Physical deep heating physical agents (ultrasound, short-waves diathermy and microwaves) were beneficial to manage pain and other variables in individuals with osteoarthritis in different levels of severity, especially in the long term. However, these effects are better observed when applied simultaneously with kinesiotherapy.

Osteoarthritis and the role of corticosteroid injections: The four groups

Background: Corticosteroid injections are commonly used in the treatment of pain in osteoarthritis. A question that is frequently asked is ‘how many corticosteroid injections can be used’ and the answers given appear to be empirical.Aim: To determine how many corticosteroid injections should be used in osteoarthritis.Methods: PubMed was used to identify articles using terms appropriate to each heading. We reviewed the clinical course of osteoarthritis with evidence from studies of pain and function, radiology, inflammation, and biomechanics. We reviewed possible pain mechanisms and the evidence for the effects and side effects of corticosteroid injections. The conclusions were drawn from an evaluation of the information presented.Results: The reviews led to a classification of osteoarthritis into four groups: improvement, slow/non-progression (the largest group), rapid progression, and chronic pain, and to an evidence-based recommendation for use of corticosteroid injections in each of the four groups.Con...