Intratendinous Injection of Hyaluronate Induces Acute Inflammation: A Possible Detrimental Effect

Abstract Hyaluronate (HA) is therapeutic for tendinopathy, but an intratendinous HA injection is usu- ally painful; thus, it is not suggested for clinical practice. However, there are no studies on the histopathological changes after an intratendinous HA injection.Wehypothesized that an HA injection would induce more-acute inflammation than that induced by an injection of phosphate buffered saline (PBS). Thirty-two rats were randomly divided into 4 post-injection groups (n = 8): day 3, day 7, day 28, and day 42. HA (0.1 c.c.) was, using ultrasound guid- ance, intratendinously injected into each left Achilles tendon, and PBS (0.1 c.c.) into each right one. For each group, both Achilles tendons of 3 control-group rats (n = 6) were given only needle punctures. The histopathological score, ED1+ and ED2+ macrophage densi- ties, interleukin (IL)-1β expression, and the extent of neovascularization were evaluated. In both experimental groups, each Achilles tendon showed significant histopathological changes and inflammation compatible with acute tendon injury until day 42. The HA group showed more-significant (p < 0.05) histopathological changes, higher ED1+ and ED2+ mac- rophage density, and higher IL-1β expression than did the PBS group. The neovasculariza- tion area was also significantly (p < 0.05) greater in the HA group, except on day 3. Both HA and PBS induced acute tendon injury and inflammation, sequential histopathological changes, ED1+ and ED2+ macrophage accumulation, IL-1β expression, and neovasculari- zation until post-injection day 42.HA induced more-severe injury than did PBS. Therefore, an intratendinous HA injection should be avoided. Introduction