Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2011
ReviewUpdate on peripheral mechanisms of pain: beyond prostaglandins and cytokines.
The peripheral nociceptor is an important target of pain therapy because many pathological conditions such as inflammation excite and sensitize peripheral nociceptors. Numerous ion channels and receptors for inflammatory mediators were identified in nociceptors that are involved in neuronal excitation and sensitization, and new targets, beyond prostaglandins and cytokines, emerged for pain therapy. This review addresses mechanisms of nociception and focuses on molecules that are currently favored as new targets in drug development or that are already targeted by new compounds at the stage of clinical trials--namely the transient receptor potential V1 receptor, nerve growth factor, and voltage-gated sodium channels--or both.
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Arthritis Res. Ther. · Jan 2011
Randomized Controlled TrialA randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee.
AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee. ⋯ The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed.
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Arthritis Res. Ther. · Jan 2011
ReviewThe role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia.
Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids).
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Arthritis Res. Ther. · Jan 2011
Editorial CommentFibromyalgia, myofascial pain, tender points and trigger points: splitting or lumping?
Myofascial trigger points (MTPs) have long been a contentious issue in relation to fibromyalgia, and poorly defined pain complaints in general. Can MTPs be reproducibly identified? Do MTPs have valid objective findings, such as spontaneous electromyographic activity, muscle microdialysis evidence for an inflammatory milieu or visualization with newer ultrasound techniques? Is fibromyalgia a syndrome of multiple MTPs, or is focal muscle tenderness a manifestation of central sensitization? These issues are discussed with relevance to a recent paper reporting that manual palpation of active MTPs elicits the spontaneous pain experienced by fibromyalgia patients.
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The objective of this study was to investigate the contemporary incidence of gout, examine potential risk factors, and evaluate specific gout treatment patterns in the general population. ⋯ The contemporary incidence of gout in UK remains substantial. In this general population cohort, associations with previously purported risk factors were evident including psoriasis, heart failure, hypertriglyceridemia, and cyclosporine therapy. Use of gout-specific treatment has remained relatively constant in recent years except for an increase of colchicine.