IntroductionAnimal models currently used in osteoarthritis-associated pain research inadequately reproduce the initiating events and structural pathology of human osteoarthritis. Conversely, intra-articular injection of collagenase is a structurally relevant model, as it induces articular degeneration both by digesting collagen from cartilage and by causing articular instability, thereby reproducing some of the main events associated with osteoarthritis onset and development. Here, we evaluated if the intra-articular injection of collagenase can be an alternative model to study nociception associated with osteoarthritis.MethodsOsteoarthritis was induced by two intra-articular injections of either 250 U or 500 U of collagenase into the left knee joint of adult male Wistar rats. A six weeks time-course assessment of movement- and loading-induced nociception was performed by the Knee-Bend and CatWalk tests. The effect of morphine, lidocaine and diclofenac on nociceptive behaviour was evaluated in animals injected with 500 U of collagenase. Joint histopathology was scored for both doses throughout time. The expression of transient receptor potential vanilloid 1 (TRPV1) in ipsilateral dorsal root ganglia (DRG) was evaluated.ResultsAn increase in nociceptive behaviour associated with movement and loading of affected joints was observed after intra-articular collagenase injection. With the 500 U dose of collagenase, there was a significant correlation between the behavioural and the histopathological osteoarthritis-like structural changes developed after six weeks. One week after injection of 500 U collagenase, swelling of the injected knee and inflammation of the synovial membrane were also observed, indicating the occurrence of an early inflammatory reaction. Behavioural changes induced by the 500 U dose of collagenase were overall effectively reversed by morphine and lidocaine. Diclofenac was effective one week after injection. TRPV1 expression increased six weeks after 500 U collagenase injection. ConclusionWe conclude that the intra-articular injection of 500 U collagenase in the knee of rats can be an alternative model for the study of nociception associated with osteoarthritis, since it induces significant nociceptive alterations associated with relevant osteoarthritis-like joint structural changes.

Agrimony (Agrimonia eupatoria L.) (Ae) is used in traditional medicine to treat inflammatory and oxidative related diseases. Therefore, this study focuses on the anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic compounds characterization was achieved by HPLC-PDA-ESI/MSn. To evaluate antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity of AeI was investigated in LPS-stimulated macrophages by measuring the NO production. In vivo anti-inflammatory activity was validated using the mouse carrageenan-induced paw edema model. Peripheral and central analgesic potential was evaluated using the acetic acid-induced writhing and hot-plate tests, respectively, as well as the formalin assay to assess both activities. The safety profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays, respectively. Vitexin, quercetin O-galloyl-hexoside, and kaempferol O-acetyl-hexosyl-rhamnoside were referred to in this species for the first time. AeI and mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF being more active than AeI. In vivo anti-inflammatory and analgesic activities were verified for both samples at concentrations devoid of toxicity. Agrimony infusion and, mainly, AePF are potential sources of antiradical and anti-inflammatory polyphenols.

Cymbopogon citratus is one of the most common herbs used in folk medicine due to its anti-inflammatory and antioxidant properties. Taking into account these properties showed on in vitro assays, the aim of this study was to evaluate the anti-inflammatory and analgesic activities of C. citratus leaves infusion (CcE) and its flavonoid-rich (CcF) and tannin-rich (CcT) fractions. The evaluation of the anti-inflammatory activity was performed in the carrageenan-induced rat paw oedema model. Both central and peripheral analgesic activities were evaluated in mice through the hot plate test and the acetic acid-induced writhing test, respectively. In the acute inflammation model, the statistically significant results obtained in percentage of oedema inhibition were 70.80 and 82.30% for CcE (34.12 and 68.24 mg kgG , respectively), 59.00% for CcF 1 (7.42 mg kgG), 61.00% for CcT (5.96 mg kgG) and 84.00% for positive control group 1 1 (10 mg kgG). For the peripheral pain evaluation, statistically significant results showed a pain 1 reduction of 57.00% for CcE (136.48 mg kgG), 54.60% for CcF (14.8 mg kgG), 52.20% for CcT 1 1 (11.92 mg kgG) and 83.00% for positive control group. This study demonstrates that C. citratus 1 infusion compounds are able to reduce inflammation and peripheral pain in vivo, with polyphenols showing a significant contribution for these activities.

The fragmentation of the literature on intermediaries between the university and industry has led to a disorganised and confused theoretical landscape. This research addresses this gap in the literature by proposing an analytical tool that can be used as guidance. For this purpose, this work provides a taxonomy of these intermediaries and classifies them into five different classes. To this end, we review 125 studies on university–industry cooperation (UIC) intermediaries. In addition to the general and innovation-related information, we extracted specific data related to the relevant UIC intermediaries from each article, i.e. the type(s) of intermediary addressed and its identified functions. This taxonomy is based on twenty-two functions identified in the UIC intermediary literature and thirteen UIC intermediary types. The five proposed classes of intermediaries are specialised in five different roles. This integrative background can be applied in future research and in the definition of policy-based guidelines.