Accepted

Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 μg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 μg/L). Fibronectin levels were independent of endometriosis stage ( = 0.874, = 0.469). No significant differences were observed in collagen IV levels ( = 0.385, = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

The Demand and Ability Protocol (DAP) is used in three-party meetings involving an employee, an employer, and a representative from the rehabilitation team. The aim of this study is to investigate the inclusion of an intervention using the DAP in an interdisciplinary pain rehabilitation programme (IPRP) compared to usual care. This non-randomised controlled trial included patients assigned to an IPRP in Sweden. The intervention group received a DAP intervention targeting their work situation in addition to the usual care provided by the IPRP. The control group received IPRP only. Outcome measures were collected from the Swedish Quality Registry for Pain Rehabilitation. Results demonstrated improvements in both groups regarding self-reported anxiety, depression and EQ5D. Sleep was improved in the intervention group but not in the control group. No statistical differences in outcomes were observed between the groups. In conclusion, adding the DAP intervention to IPRP seemed to have the potential to improve sleep among the patients, which may indicate an overall improvement regarding health outcomes from a longer perspective. The results were less clear, however, regarding the work-related outcomes of sickness absence and workability.

Although pain dysfunction is increasingly observed in Huntington disease (HD), the underlying mechanisms still unknown. As a crucial huntington-associated protein, HAP1 is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) where are regarded as "primary sensory center", indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)- and chronic constriction injury (CCI)-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca2+ influx and then influence BDNF synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1 deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion and inflammatory responses and ultimately influences neuropathic pain progression.