The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives

Although still used by hundreds of millions of people worldwide, the mechanism of the analgesic action of the pyrazolone derivatives (PDs), dipyrone, propyphenazone and antipyrine remains unknown. The transient receptor potential ankyrin 1 (TRPA1) channel, expressed by nociceptors, is emerging as a major pain transduction pathway. We hypothesized that PDs target the TRPA1 channel and by this mechanism produce their analgesic effect

Non-steroidal anti-inflammatory drugs for low back pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medications worldwide and are widely used for patients with low-back pain. Selective COX-2 inhibitors are currently available and used for patients with low-back pain. The objective was to assess the effects of NSAIDs and COX-2 inhibitors in the treatment of non-specific low-back pain and to assess which type of NSAID is most effective. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials up to and including June 2007 if reported in English, Dutch or German. We also screened references given in relevant reviews and identified trials. Randomised trials and double-blind controlled trials of NSAIDs in non-specific low-back pain with or without sciatica were included. Two review authors independently extracted data and assessed methodological quality. All studies were also assessed on clinical relevance, from which no further interpretations or conclusions were drawn. If data were considered clinically homogeneous, a meta-analysis was performed. If data were lacking for clinically homogeneous trials, a qualitative analysis was performed using a rating system with four levels of evidence (strong, moderate, limited, no evidence). In total, 65 trials (total number of patients = 11,237) were included in this review. Twenty-eight trials (42%) were considered high quality. Statistically significant effects were found in favour of NSAIDs compared to placebo, but at the cost of statistically significant more side effects. There is moderate evidence that NSAIDs are not more effective than paracetamol for acute low-back pain, but paracetamol had fewer side effects. There is moderate evidence that NSAIDs are not more effective than other drugs for acute low-back pain. There is strong evidence that various types of NSAIDs, including COX-2 NSAIDs, are equally effective for acute low-back pain. COX-2 NSAIDs had statistically significantly fewer side-effects than traditional NSAIDs. The evidence from the 65 trials included in this review suggests that NSAIDs are effective for short-term symptomatic relief in patients with acute and chronic low-back pain without sciatica. However, effect sizes are small. Furthermore, there does not seem to be a specific type of NSAID which is clearly more effective than others. The selective COX-2 inhibitors showed fewer side effects compared to traditional NSAIDs in the RCTs included in this review. However, recent studies have shown that COX-2 inhibitors are associated with increased cardiovascular risks in specific patient population

Effect sizes of non-surgical treatments of non-specific low-back pain.

Numerous randomized trials have been published investigating the effectiveness of treatments for non-specific low-back pain (LBP) either by trials comparing interventions with a no-treatment group or comparing different interventions. In trials comparing two interventions, often no differences are found and it raises questions about the basic benefit of each treatment. To estimate the effect sizes of treatments for non-specific LBP compared to no-treatment comparison groups, we searched for randomized controlled trials from systematic reviews of treatment of non-specific LBP in the latest issue of the Cochrane Library, issue 2, 2005 and available databases until December 2005. Extracted data were effect sizes estimated as Standardized Mean Differences (SMD) and Relative Risk (RR) or data enabling calculation of effect sizes. For acute LBP, the effect size of non-steroidal anti-inflammatory drugs (NSAIDs) and manipulation were only modest (ES: 0.51 and 0.40, respectively) and there was no effect of exercise (ES: 0.07). For chronic LBP, acupuncture, behavioral therapy, exercise therapy, and NSAIDs had the largest effect sizes (SMD: 0.61, 0.57, and 0.52, and RR: 0.61, respectively), all with only a modest effect. Transcutaneous electric nerve stimulation and manipulation had small effect sizes (SMD: 0.22 and 0.35, respectively). As a conclusion, the effect of treatments for LBP is only small to moderate. Therefore, there is a dire need for developing more effective interventions. © 2007 Springer-Verlag

Outcome of non-invasive treatment modalities on back pain: an evidence-based review.

At present, there is an increasing international trend towards evidence-based health care. The field of low back pain (LBP) research in primary care is an excellent example of evidence-based health care because there is a huge body of evidence from randomized trials. These trials have been summarized in a large number of systematic reviews. This paper summarizes the best available evidence from systematic reviews conducted within the framework of the Cochrane Back Review Group on non-invasive treatments for non-specific LBP. Data were gathered from the latest Cochrane Database of Systematic Reviews 2005, Issue 2. The Cochrane reviews were updated with additional trials, if available. Traditional NSAIDs, muscle relaxants, and advice to stay active are effective for short-term pain relief in acute LBP. Advice to stay active is also effective for long-term improvement of function in acute LBP. In chronic LBP, various interventions are effective for short-term pain relief, i.e. antidepressants, COX2 inhibitors, back schools, progressive relaxation, cognitive–respondent treatment, exercise therapy, and intensive multidisciplinary treatment. Several treatments are also effective for short-term improvement of function in chronic LBP, namely COX2 inhibitors, back schools, progressive relaxation, exercise therapy, and multidisciplinary treatment. There is no evidence that any of these interventions provides long-term effects on pain and function. Also, many trials showed methodological weaknesses, effects are compared to placebo, no treatment or waiting list controls, and effect sizes are small. Future trials should meet current quality standards and have adequate sample size