The application of topical diclofenac has been suggested as a possible treatment for Achilles tendinopathy. Our aim was to answer the question, is topical diclofenac more effective than placebo for ...the treatment of Achilles tendinopathy?.
67 participants with persistent midportion or insertional Achilles tendinopathy were randomly assigned to receive a 4 week course of 10% topical diclofenac (n = 32) or placebo (n = 35). The a priori primary outcome measure was change in severity of Achilles tendinopathy (VISA-A score) at 4 and 12 weeks. Secondary outcome measures included numeric pain rating, and patient-reported change in symptoms using a 7 point scale, from substantially worse to substantially better. Pressure pain threshold (N) and transverse tendon stiffness (N/m) were measured over the site of maximum Achilles tendon pathology at baseline and 4 weeks.
There were no statistically or clinically significant differences between the diclofenac and placebo groups in any of the primary or secondary outcome measures at any timepoint. Average VISA-A score improved in both groups (p<0.0001), but the improvements were marginal: at 4 weeks, the improvements in VISA-A were 9 (SD 11) in the diclofenac group and 8 (SD 12) in the placebo group, and at 12 weeks the improvements were 9 (SD 16) and 11 (SD13) respectively-these average changes are smaller than the minimum clinically important difference of the VISA-A.
The regular application of topical diclofenac for Achilles tendinopathy over a 4 week period was not associated with superior clinical outcomes to that achieved with placebo.
Ingestion of monosodium glutamate (MSG) causes headache, nausea and craniofacial tenderness in healthy individuals. The present study explored whether MSG produces behavioural signs of headache, ...nausea and changes in craniofacial sensitivity in rats. The behavior of male and female Sprague Dawley rats was video recorded before and after intraperitoneal (i.p.) injections of either MSG (1-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg) or normal saline. Behaviors (grimace score, head-flicks, rearing, head scratches, facial grooming, lying-on-belly and temporalis muscle region mechanical withdrawal threshold (MT)) were evaluated. Facial cutaneous temperature of the nose and forehead was measured before and after i.p. injections via infrared thermography. Plasma glutamate and calcitonin-gene related peptide (CGRP) concentrations after administration of 1000 mg/kg MSG were measured in anesthetized rats. MSG induced nocifensive, headache- and nausea-like behaviors in a dose-related manner but had no effect on MT. MSG (1000 mg/kg) induced a significantly greater frequency of headache-like behavior in females, but a longer duration of nausea-like behavior in males. MSG produced a prolonged increase in plasma glutamate and CGRP concentrations. Co-administration of the median effective dose of MSG (350 mg/kg) with GTN (10 mg/kg) amplified headache-like behaviors, induced significant craniofacial sensitivity and produced increased nausea-like behaviour. Co-administration of sumatriptan or naproxen with MSG (1000 mg/kg), significantly attenuated MSG-induced nocifensive and headache-like behaviors. Our data suggests that systemic administration of MSG to rats induces behavioral correlates of headache and nausea. This model may offer another avenue for research on the mechanism and treatment of primary headache disorders such as migraine.
We present an algorithm for the retrieval of cloud droplet size distribution parameters (effective radius and variance) from the Research Scanning Polarimeter (RSP) measurements. The RSP is an ...airborne prototype for the Aerosol Polarimetery Sensor (APS), which was on-board of the NASA Glory satellite. This instrument measures both polarized and total reflectance in 9 spectral channels with central wavelengths ranging from 410 to 2260nm. The cloud droplet size retrievals use the polarized reflectance in the scattering angle range between 135° and 165°, where they exhibit the sharply defined structure known as the rain- or cloud-bow. The shape of the rainbow is determined mainly by the single scattering properties of cloud particles. This significantly simplifies both forward modeling and inversions, while also substantially reducing uncertainties caused by the aerosol loading and possible presence of undetected clouds nearby. In this study we present the accuracy evaluation of our algorithm based on the results of sensitivity tests performed using realistic simulated cloud radiation fields.
► We present an algorithm for retrieval of cloud droplet size from polarized rainbow. ► Polarized rainbow shape is determined by single scattering of cloud droplets. ► The algorithm is designed for the airborne Research Scanning Polarimeter (RSP). ► RSP measures polarized and total reflectance at 9 wavelengths between 410 to 2260nm. ► We evaluate the algorithm using tests on simulated cloud radiation fields.
Remote sensing of aerosol optical properties is difficult, but multi-angle, multi-spectral, polarimetric instruments have the potential to retrieve sufficient information about aerosols that they can ...be used to improve global climate models. However, the complexity of these instruments means that it is difficult to intuitively understand the relationship between instrument design and retrieval success. We apply a Bayesian statistical technique that relates instrument characteristics to the information contained in an observation. Using realistic simulations of fine size mode dominated spherical aerosols, we investigate three instrument designs. Two of these represent instruments currently in orbit: the Multiangle Imaging SpectroRadiometer (MISR) and the POLarization and Directionality of the Earths Reflectances (POLDER). The third is the Aerosol Polarimetry Sensor (APS), which failed to reach orbit during recent launch, but represents a viable design for future instruments. The results show fundamental differences between the three, and offer suggestions for future instrument design and the optimal retrieval strategy for current instruments. Generally, our results agree with previous validation efforts of POLDER and airborne prototypes of APS, but show that the MISR aerosol optical thickness uncertainty characterization is possibly underestimated.
Differences in glutamate-evoked pain between the temporalis and masseter muscles, and between men and women were shown. There is a possibility that treatment of patients with chronic myofascial ...temporomandibular disorder with local injections of ketamine at the concentration used in this study may be effective in reducing muscle pain.
Pain in myofascial temporomandibular disorder (TMD) can affect both the masseter and temporalis muscles. Glutamate injection into the masseter muscle evokes pain that is greater in men than in women and this pain is attenuated by co-injection of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine (10mmol/L) in men. Animal studies suggested that pain induced by peripheral NMDA receptor activation could differ between the temporalis and masseter muscles and between men and women. The study aims were to investigate differences in glutamate-evoked pain between these muscles and the effectiveness of ketamine to attenuate glutamate-evoked pain in both genders. Pain and mechanical sensitivity were induced in 2 sessions of an experiment in 14 women and 16 men by repeated injections of glutamate (0.5mol/L) with and without ketamine (20mmol/L) into the masseter and temporalis muscles. Two injections were applied into the same masseter muscle and 2 injections into the same anterior temporalis muscle at each session. Visual analogue scale (VAS) pain intensities and pain drawing areas were assessed. Glutamate-evoked pain and pain drawing area were significantly greater from the temporalis muscle than from the masseter muscle (P<.02) in both genders. Women reported significantly greater glutamate-evoked masseter muscle pain than men (P<.03). Co-injection of ketamine, at higher dose than previously used, was equally effective in attenuating glutamate-evoked pain from both muscles in both genders (P<.01). The current findings indicate that the characteristics of pain generated by intramuscular injection of glutamate vary for different masticatory muscles and may be partially generated through activation of peripheral NMDA receptors.
Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced ...sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 μg/ml, 10 μl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2-7 m/s) than fast Aδ-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.
Cannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, ...however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management.
Our purpose was to systematically review the literature on the effectiveness of peripherally acting cannabinoids for pain management.
We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed databases. Included studies examined the effect of topical/peripherally administered cannabinoids on pain ratings in humans, as well as pain-related outcomes in animals (eg, paw withdrawal). Due to a lack of trials, human studies were summarized in a narrative synthesis. Separate meta-analyses were performed for animal studies using radiant tail flick or paw withdrawal outcomes.
Our search yielded 1182 studies following removal of duplicates, with 46 studies (6 human, 40 animal) included. Human studies (one randomized controlled trial and five case studies/series) reported no adverse events to topical cannabinoids and preliminary evidence of decreased pain ratings. Animal studies reporting tail flick (5) (2.81, 95% CI 1.93 to 3.69, p<0.001) and mechanical withdrawal (11) (2.74, 95% CI 1.82 to 3.67, p<0.001) reported prolonged responses (analgesia) in peripheral cannabinoid groups compared with controls.
Preclinical animal studies provided low-quality evidence for peripherally administered cannabinoids to provide regional, antinociceptive effects. The scarcity of high-quality human studies underscores the need to translate preclinical evidence into well-controlled human trials.
3D effects cause substantial underestimation of cloud optical thickness (COT) in airborne and satellite retrievals based on 1D radiative transfer computations (such as in the case of widely used ...bispectral technique). For a single-layer isolated cloud we propose a simple linear correction of the retrieved COT with the renormalization factor dependent on the cloud’s aspect ratio (the ratio between vertical and horizontal dimensions of the cloud). This is an empirical assumption which we successfully test using synthetic 3D RT data. We introduce a heuristic “block model” of 3D radiative effects and show that the functional form of the renormalization factor is consistent with the process of radiation escape from cloud sides in an essentially 3D geometry. We also extend the block model to the case of single-layer broken cloud field with radiative interaction between the neighboring clouds. In this case the renormalization factor depends also on the distance between clouds.
Background
In skeletal muscle, free nerve endings are mostly located within the connective tissue. However, the distribution of sensory afferent fibres in healthy human masseter muscle tissues has ...not been studied.
Objectives
Primarily to investigate human masseter muscle nerve fibre densities as well as expression of NR2B receptors, substance P (SP) and nerve growth factor (NGF), and secondarily to compare this between a) nerve fibres associated with myocytes and within connective tissue; b) sexes; and c) ages.
Methods
Microbiopsies of the masseter muscle were obtained from 60 sex‐ and age‐matched healthy participants. Biopsy sections were analysed using immunohistochemistry and were visualised with a Leica TCS SPE confocal microscope. The Mann‐Whitney U test was used for statistical analyses.
Results
The density of nerve fibres within connective tissue was significantly greater than in nerve fibres associated with myocytes (P < .001). Nerve fibres within connective tissue expressed SP alone or together with NR2B significantly more often than those associated with myocytes (P < .001). The frequency of nerve fibres, which expressed SP alone or in combination with NR2B or NGF, was significantly greater in women than in men (P < .050). Moreover, the co‐expression of the three markers together was inversely correlated with age in women (P < .002).
Conclusions
There is a higher density and greater expression of sensory nerve fibres within the connective tissue than associated with myocytes in healthy human masseter muscle. This suggests that nerve fibres within connective tissue are more involved in nociception than nerve fibres associated with myocytes.
PDF
