Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain

OBJECTIVE: Mechanisms responsible for osteoarthritic pain remain poorly understood and current analgesic therapies are often insufficient. We have characterized and pharmacologically tested the pain phenotype of a non-invasive mechanical joint loading (MJL) model of osteoarthritis thus providing an alternative murine model for osteoarthritic pain. METHODS: The right knees of male mice (12-week-old, C57BL/6) were loaded at 9N or 11N (40 cycles, three times/week for two weeks). Behavioural measurements of limb disuse, mechanical and thermal hypersensitivity were acquired before MJL and monitored for six weeks post-loading. The severity of articular cartilage lesions was determined post-mortem with the OARSI grading scheme. Furthermore, 9N-loaded mice were treated for four weeks with diclofenac (10mg/kg), gabapentin (100mg/kg) or anti-Nerve Growth Factor (3mg/kg). RESULTS: Mechanical hypersensitivity and weight-bearing worsened significantly in 9N- and 11N-loaded mice two weeks post-loading compared to baseline values and non-loaded controls. Maximum OA scores of ipsilateral knees confirmed increased cartilage lesions in 9N- (2.8±0.2) and 11N-loaded (5.3±0.3) mice compared to non-loaded controls (1.0±0.0). Gabapentin and diclofenac restored pain behaviours to baseline values after two weeks of daily treatment, with gabapentin being more effective than diclofenac. A single injection of anti-NGF alleviated nociception two days after treatment and remained effective for two weeks with a second dose inducing stronger and more prolonged analgesia. CONCLUSION: Our results show that MJL induces OA lesions and a robust pain phenotype that can be reversed using analgesics known to alleviate OA pain in patients. This establishes the use of MJL as an alternative model for osteoarthritic pain

Cytomegalovirus distribution and evolution in hominines

Herpesviruses are thought to have evolved in very close association with their hosts. This is notably the case for cytomegaloviruses (CMVs; genus Cytomegalovirus) infecting primates, which exhibit a strong signal of co-divergence with their hosts. Some herpesviruses are however known to have crossed species barriers. Based on a limited sampling of CMV diversity in the hominine (African great ape and human) lineage, we hypothesized that chimpanzees and gorillas might have mutually exchanged CMVs in the past. Here, we performed a comprehensive molecular screening of all 9 African great ape species/subspecies, using 675 fecal samples collected from wild animals. We identified CMVs in eight species/subspecies, notably generating the first CMV sequences from bonobos. We used this extended dataset to test competing hypotheses with various degrees of co-divergence/number of host switches while simultaneously estimating the dates of these events in a Bayesian framework. The model best supported by the data involved the transmission of a gorilla CMV to the panine (chimpanzee and bonobo) lineage and the transmission of a panine CMV to the gorilla lineage prior to the divergence of chimpanzees and bonobos, more than 800,000 years ago. Panine CMVs then co-diverged with their hosts. These results add to a growing body of evidence suggesting that viruses with a double-stranded DNA genome (including other herpesviruses, adenoviruses, and papillomaviruses) often jumped between hominine lineages over the last few million years.Peer Reviewe