Substance P releases and augments the morphine-evoked release of adenosine from spinal cord

The effects of substance P on the morphine-evoked release of adenosine were examined. Substance P alone produced a multiphasic effect on release of adenosine, with release occurring at low nanomolar concentrations and at a micromolar concentration, but not at intermediate concentrations. An inactive dose of substance P augmented the morphine-evoked release of adenosine at a nanomolar concentration of morphine. Release of adenosine by substance P alone (1 nM) or substance P/morphine (100 nM/10 nM) was Ca2(+)-dependent and originated from capsaicin-sensitive nerve terminals

Involvement of Calcium Channels in Depolarization-Evoked Release of Adenosine from Spinal Cord Synaptosomes

The potential involvement of L- and N-type voltage-sensitive calcium (Ca2+) channels and a voltage-independent receptor-operated Ca2+ channel in the release of adenosine from dorsal spinal cord synaptosomes induced by depolarization with K+ and capsaicin was examined. Bay K 8644 (10 nM) augmented release of adenosine in the presence of a partial depolarization with K+ (addition of 6 mM) but not capsaicin (1 and 10 microM). This augmentation was dose dependent from 1 to 10 nM and was followed by inhibition of release from 30 to 100 nM. Nifedipine and nitrendipine inhibited the augmenting effect of Bay K 8644 in a dose-dependent manner, but neither antagonist had any effect on release of adenosine produced by K+ (24 mM) or capsaicin (1 and 10 microM). omega-Conotoxin inhibited K(+)-evoked release of adenosine in a dose-dependent manner but had no effect on capsaicin-evoked release. Ruthenium red blocked capsaicin-induced release of adenosine but had no effect on K(+)-evoked release. Although L-type voltage-sensitive Ca2+ channels can modulate release of adenosine when synaptosomes are partially depolarized with K+, N-type voltage-sensitive Ca2+ channels are primarily involved in K(+)-evoked release of adenosine. Capsaicin-evoked release of adenosine does not involve either L- or N-type Ca2+ channels, but is dependent on a mechanism that is sensitive to ruthenium red

Qigong and Fibromyalgia circa 2017

Qigong is an internal art practice with a long history in China. It is currently characterized as meditative movement (or as movement-based embodied contemplative practice), but is also considered as complementary and alternative exercise or mind–body therapy. There are now six controlled trials and nine other reports on the effects of qigong in fibromyalgia. Outcomes are related to amount of practice so it is important to consider this factor in overview analyses. If one considers the 4 trials (201 subjects) that involve diligent practice (30–45 min daily, 6–8 weeks), there are consistent benefits in pain, sleep, impact, and physical and mental function following the regimen, with benefits maintained at 4–6 months. Effect sizes are consistently in the large range. There are also reports of even more extensive practice of qigong for 1–3 years, even up to a decade, indicating marked benefits in other health areas beyond core domains for fibromyalgia. While the latter reports involve a limited number of subjects and represent a self-selected population, the marked health benefits that occur are noteworthy. Qigong merits further study as a complementary practice for those with fibromyalgia. Current treatment guidelines do not consider amount of practice, and usually make indeterminate recommendations

Clonidine reverses methylxanthine-induced potentiation of baclofen antinociception.

The effect of clonidine on the antinociceptive effect of methylxanthine/baclofen and dopamine antagonist/baclofen combinations was examined to determine if alterations in noradrenaline turnover might mediate the potentiating effect of these agents. Clonidine alone had intrinsic activity in the tail flick test, so a dose and treatment schedule which produced a plateau effect was chosen. Clonidine pretreatment did not significantly alter the effect of baclofen alone, but reversed the potentiation of the action of baclofen produced by both theophylline and isobutylmethylxanthine. The intrinsic effect of isobutylmethylxanthine also was reversed. Combinations of dopamine antagonists and baclofen were potentiated or unaffected by clonidine. A possible interpretation of these results is that mutual interactions by baclofen and methylxanthines with descending noradrenergic pathways mediate the methylxanthine-induced potentiation of the antinociceptive effect of baclofen. A more specific determination of noradrenergic pathways involved in the action of baclofen will require the use of more specific alternative approaches

Extension Trial of Qigong for Fibromyalgia: A Quantitative and Qualitative Study

This extension trial is an open-label observational trial of 20 subjects with fibromyalgia who undertook level 2 Chaoyi Fanhuan Qigong (CFQ) training following an earlier controlled trial of level 1 CFQ. Subjects practiced 60 min/day for 8 weeks and continued some daily practice for 6 months. Quantitative measures, assessed at baseline, 8 weeks, 4 and 6 months, were of pain, impact, sleep, physical and mental functions, and practice time. Qualitative comments also were recorded. Compared to baselines, CFQ practice led to significant improvements in pain, impact, sleep, and physical function in the 13 subjects (65%) who completed the trial; changes were present at 8 weeks and were maintained for the 6-month trial duration. A highly motivated subgroup of N=5, who practiced the most, had the best outcomes in terms of end symptomology, and qualitative comments indicated health benefits in other domains as well. Qualitative comments by the remaining N=8 trial completers and N=7 withdrawals indicate different experiences with the practice. This extension trial indicates that diligent CFQ practice over time produces significant health gains in fibromyalgia in a subset of individuals. Future studies will need to address factors that might predispose to favourable outcomes

A Qualitative Systematic Review of Head-to-Head Randomized Controlled Trials of Oral Analgesics in Neuropathic Pain

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug.OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP.METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality.RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices.Peer Reviewe

A Qualitative Systematic Review of Head-to-Head Randomized Controlled Trials of Oral Analgesics in Neuropathic Pain

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug