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Osteoarthritis (OA) is the most common cause to lead to chronic pain. Sensitization of pain pathways including central sensitization and peripheral sensitization has been regarded as a major cause of OA pain refractory to treatment. Addressing peripheral sensitization or central sensitization alone may not adequately treat OA pain. In our previous studies, botulinum toxin type A (BoNT/A) has been shown to reduce peripheral sensitization for analgesic effects. In addition, transcranial direct current stimulation (tDCS) has also been suggested to reduce central sensitization for analgesia. The present study was designed to investigate whether BoNT/A in combination with tDCS has better analgesic effects than isolated treatment to alleviate OA-induced chronic pain in rats. The Von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. The expression level of N-methyl-D-aspartate receptor-2B (NMDAR2B) was evaluated in midbrain periaqueductal gray (PAG) by Western blot the Immunohistochemistry staining after different treatments. The results showed that the combined treatment of BoNT/A and tDCS better improved the pain-related behaviors and significantly increased the expression level of NMDAR2B protein in PAG than each isolated treatment. These results suggested that the combined treatments for relief of chronic pain were more obvious than each isolated treatment. The combination of BoNT/A and tDCS may relieve pain by increasing N-methyl-D-aspartate (NMDA) receptors in the PAG, and then the descending inhibitory systems were activated to modulate peripheral and central sensitization.

Neuropathic pain in osteoarthritis is one of the reasons why the pain is difficult to treat, and P2X4R plays an important role in neuropathic pain. In addition, BoNT/A has been proven to have analgesic effects on both neuropathic pain and osteoarthritis, but its exact mechanism is still unknown. This study aims to investigate the relationship between the analgesic effect of BoNT/A on osteoarthritis and the expression of P2X4R in spinal cord microglia. The analgesic effect was compared between BoNT/A and compound betamethasone. Western blot analysis was used to examine the expression of P2X4R and BDNF proteins in the spinal cord. Immunohistochemistry was used to determine the cellular location of P2X4R. Mechanical allodynia and weight asymmetry were identified using the hind paw withdrawal threshold and weight bearing test. The results showed that intra-articular injection of MIA induced persistent mechanical allodynia and weight asymmetry in rats. Both BoNT/A and betamethasone could relieve pain behavior in rats, but BoNT/A had a more obvious effect and lasted longer. Furthermore, BoNT/A could reverse the MIA-induced overexpression of BDNF and P2X4R in the spinal dorsal horn. To sum up, BoNT/A is more effective than betamethasone in relieving MIA-induced osteoarthritis pain in rats, and its analgesic effect may be related to the regulation of P2X4R-mediated BDNF release in spinal microglia and the relief of neuropathic pain in osteoarthritis.

China has shut down and abandoned a substantial number of coal mines since 1999, which have been releasing methane (CH

Hydrogels have been applied in flexible strain sensors due to good conductivity, stretchability and sensitivity to strain. However, gaining rapid and effective self-healing hydrogels for the durability of flexible strain sensors is still a challenging. Herein, we report a tough, conductive hydrogel that can rapidly self-healing at room temperature. The hydrogel is fabricated by incorporating polystyrene-co-poly (N,N-dimethylacrylamide) (P (St-co-DMAA)) microspheres prepared by emulsion polymerization into hydrophobic association hydrogels networks composed of polyacrylamide-co-poly (hexadecyl methacrylate) (PAAm-co-PHMA), sodium dodecyl sulfate (SDS) and sodium chloride (NaCl). The hydrogel possesses a dual dynamic crosslinking comprising of multiple hydrogen bonds and hydrophobic association. The multiple hydrogen bonds formed between the outer regions of microspheres and PAAm chains provide rapid self-healing of hydrogels and contribute to re-association of hydrophobic chains and further improve self-healing efficiency. (99% Self-healing efficiency at room temperature for 2 h). At the same time, the dual crosslinking also gives the hydrogel good mechanical properties and fatigue resistance. In addition, the existence of sodium ions and chloride ions also endowed the hydrogel high sensitive deformation-dependent conductivity, make the hydrogel able to sensitive sensing of large and small strain signals (e.g. finger bending and breathing). And the sensing ability of hydrogel can be also recovered quickly after self-healing. Therefore, this strategy will expand the application range of a new generation of hydrogels such as self-healing conductors, robotic electronic skin and strain sensors, etc.

We investigated the effect of different concentrations of elastase on the aneurysm formation rate in the abdominal aortic aneurysm (AAA) model induced by low-pressurized abdominal aortic perfusion of elastase in rabbits. Fifty male New Zealand white rabbits were randomly divided into five groups (