Numerous exploratory, proof-of-concept and interventional studies have used histaminergic and non-histaminergic human models of itch. However, no reliability studies for such surrogate models have been conducted. This study investigated the test-retest reliability for the response to histamine- and cowhage- (5, 15, 25 spiculae) induced itch in healthy volunteers. Cowhage spiculae were individually applied with tweezers and 1% histamine was applied with a skin prick test (SPT) lancet, both on the volar forearm. The intensity of itch was recorded on a visual analogue scale and self-reported area of itch was assessed 5 and 10 min after itch provocation. Reliability of the evoked itch (area under the curve and peak intensity) was assessed by the coefficient of variation (CV), intra-class correlation coefficient (ICC), and sample size estimation for parallel and cross-over designs. Cowhage (ICC = 0.57-0.77, CVbetween = 97%, CVwithin = 41%) and histamine: (ICC = 0.83-0.93, CVbetween = 97%, CVwithin = 20%) exhibited moderate-to-excellent intra-individual reliability and moderate inter-individual reliability for the itch intensity. For a test-retest observation period of one week, SPT-delivered histamine and application of cowhage-spiculae are reproducible human models of itch. The high inter-individual and low intra-individual variability suggests cross-over designed studies when applicable.

Intramuscular injection of nerve growth factor (NGF) causes muscle hyperalgesia without immediate pain. This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5 mg) compared with 5 spatially distributed, low-dose NGF injections (1 mg, 4 cm distance) into the tibialis anterior (TA) muscles in 20 healthy subjects. Injection pain was rated on a visual analog scale. Reports of muscle pain with functional tasks (Likert scale score) and the presence of spontaneous pain were collected daily by using a diary. Pressure pain threshold (PPT), overall pain intensity (numerical rating scale), and pain areas following the TA contraction were collected at baseline; 3 hours; and 1, 3, 7, 14, and 21 days postinjection. Low immediate visual analog scale scores were associated with both injection protocols. Likert scale scores showed moderate pain intensities but no spontaneous pain, until day 12, for both injection protocols (P < .05). Reduced PPTs at the 5-and 1-mg injection sites were found after 3 hours, lasting until day 7 (P < .05). The 1-mg injection provoked decreased PPTs at day 1 (P = .036) at the proximal injection site and at day 1 (P = .02) and day 3 (P = .01) at the distal injection site. The TA muscle contraction resulted in larger pain areas and higher numerical rating scale scores at day 3 for the distributed injections compared with the single-site injection (P < .001). Perspective: Spatially distributed low-dose NGF injections induced prolonged pain, mechanical muscle hypersensitivity, and enlarged contraction-evoked pain areas. These features mirror some clinical muscle pain conditions in which diffuse pain areas and muscle hypersensitivity are present during the activities of daily living. Low-dose NGF injections may be useful for further studies of prolonged pain conditions.

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.

In contrast to asymptomatic individuals, the semispinalis cervicis muscle displays reduced and less-defined EMG activity during a multidirectional isometric contraction in patients with chronic neck pain. The altered behavior of the semispinalis cervicis is weakly associated to pressure pain sensitivity.

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