Introduction Cannabis-based medicines have a number of therapeutic indications, including anti-inflammatory and analgesic effects. The endocannabinoid receptor system, including the cannabinoid receptor 1 (CB 1 ) and receptor 2 (CB 2 ) and the endocannabinoids, are implicated in a wide range of physiological and pathophysiological processes. Pre-clinical and clinical studies have demonstrated that cannabis-based drugs have therapeutic potential in inflammatory diseases, including rheumatoid arthritis (RA) and multiple sclerosis. The aim of this study was to determine whether the key elements of the endocannabinoid signalling system, which produces immunosuppression and analgesia, are expressed in the synovia of patients with osteoarthritis (OA) or RA.

ObjectiveTo investigate the impact of an experimental model of osteoarthritis (OA) on spinal nociceptive processing and the role of the inhibitory endocannabinoid system in regulating sensory processing at the spinal level.MethodsExperimental OA was induced in rats by intraarticular injection of sodium mono-iodoacetate (MIA), and the development of pain behavior was assessed. Extracellular single-unit recordings of wide dynamic range (WDR) neurons in the dorsal horn were obtained in MIA-treated rats and saline-treated rats. The levels of endocannabinoids and the protein and messenger RNA levels of the main synthetic enzymes for the endocannabinoids (N-acyl phosphatidylethanolamine phospholipase D [NAPE-PLD] and diacylglycerol lipase α [DAGLα]) in the spinal cord were measured.ResultsLow-weight (10 gm) mechanically evoked responses of WDR neurons were significantly (P < 0.05) facilitated 28 days after MIA injection compared with the responses in saline-treated rats, and spinal cord levels of anandamide and 2-arachidonoyl glycerol (2-AG) were increased in MIA-treated rats. Protein levels of NAPE-PLD and DAGLα, which synthesize anandamide and 2-AG, respectively, were elevated in the spinal cords of MIA-treated rats. The functional role of endocannabinoids in the spinal cords of MIA-treated rats was increased via activation of cannabinoid 1 (CB1) and CB2 receptors, and blockade of the catabolism of anandamide had significantly greater inhibitory effects in MIA-treated rats compared with control rats.ConclusionOur findings provide new evidence for altered spinal nociceptive processing indicative of central sensitization and for adaptive changes in the spinal cord endocannabinoid system in an experimental model of OA. The novel control of spinal cord neuronal responses by spinal cord CB2 receptors suggests that this receptor system may be an important target for the modulation of pain in OA.

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

The colonization of biodegradable polymer scaffolds with cell populations has been established as the foundation for the engineering of a number of tissues, including cartilage, liver, and bone. Within these scaffolds, the cells encounter a porous environment in which they must migrate across the convoluted polymer surface to generate a homogenous cell distribution. Predicting the interactions between cells and pores is important if scaffold characteristics are to be optimized. Therefore, we investigated the behavior of two model cell types over a range of defined pore features. These pore features range from 5 to 90 microm in diameter and have been fabricated by photolithographic techniques. Quantitatively, the behavior of the cells is dependent on three factors: 1) percentage cell coverage of the surface; 2) pore size; and 3) cell type. Fibroblast cells displayed a co-operative pattern of cell spreading in which pores with diameters greater than the cell dimensions were bridged by groups of cells using their neighbors as supports. Endothelial cells were unable to use neighbors as support structures and failed to bridge pores greater than the cell diameter.

BackgroundClinical studies of osteoarthritis (OA) suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA) model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia) was assessed. Spinal cord microglia (Iba1 staining) and astrocyte (GFAP immunofluorescence) activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed.ResultsSeven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p < 0.05, compared to contralateral levels and compared to saline controls). Levels of activated microglia were significantly elevated at day 14 and 21 post MIA-injection. At day 28, microglia activation was significantly correlated with distal allodynia (p < 0.05). Ipsilateral spinal GFAP immunofluorescence was significantly (p < 0.01) increased at day 28, but not at earlier timepoints, in the MIA model, compared to saline controls. Repeated oral dosing (days 14-20) with nimesulide attenuated pain behaviour and the activation of microglia in the ipsilateral spinal cord at day 21. This dosing regimen also significantly attenuated distal allodynia (p < 0.001) and numbers of activated microglia (p < 0.05) and GFAP immunofluorescence (p < 0.001) one week later in MIA-treated rats, compared to vehicle-treated rats. Repeated administration of minocycline also significantly attenuated pain behaviour and reduced the number of activated microglia and decreased GFAP immunofluorescence in ipsilateral spinal cord of MIA treated rats.ConclusionsHere we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

A significant proportion, particularly of B2 fractures, were treated without revision of the stem. These were associated with a higher rate of re-operation. The treatment of B3 fractures without revision of the stem resulted in a high rate of re-operation. This demonstrates the importance of careful evaluation and accurate characterisation of the fracture at the time of presentation to ensure the correct management. There is a need for improvement in the reporting of data in case series recording the outcome of the surgical treatment of periprosthetic fractures. We have suggested a minimum dataset to improve the quality of data in studies dealing with these fractures. Cite this article: 2017;99-B(4 Supple B):17-25.

ObjectivesSystematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions.SettingMedical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015.Study eligibility criteria, participants and interventionsObservational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible.Data extraction and outcome measures2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated.ResultsThe search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3).ConclusionsSmokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.

Both scoring systems implemented provide useful measures in the characterisation of knee osteoarthritis. It is of note that an additional parameter within the OACH score over the HHGS defines the extent of the disease, where the HHGS is a grade attributed to the most representative level of the biological aggression within the OA lesions. This study has confirmed the OACH system's utility in human knee OA and is supported by a significant correlation with the established HHGS.