Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: 1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and 2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve in wild-type and TNFR1−/− mice. Anhedonia, weight loss and physical state were measured as symptoms of depression. Hippocampal neurogenesis, neuroplasticity, myelin remodeling and TNF/TNFRs expression were analyzed by immunohistochemical analysis and western blot assay. We found that neuropathic pain resulted in the development of depressive symptoms in a time dependent manner and was associated with profound hippocampal alterations such as impaired neurogenesis, reduced expression of neuroplasticity markers and myelin proteins. The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1−/− mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.

As an increasing number of states begin to legalize marijuana for either medical or recreational use, it is important to determine its effects on joint arthroplasty. The purpose of this study is to determine the impact of cannabis use on total knee arthroplasty (TKA) revision incidence, revision causes, and time to revision by analyzing the Medicare database between 2005 and 2014. A retrospective review of the Medicare database for TKA, revision TKA, and causes was performed utilizing Current Procedural Terminology (CPT) and International Classification of Disease ninth revision codes (ICD-9). Patients who underwent TKA were cross-referenced for a history of cannabis use by querying ICD-9 codes 304.30–32 and 305.20–22. The resulting group was then longitudinally tracked postoperatively for revision TKA. Cause for revision, time to revision, and gender were also investigated. Our analysis returned 2, 718,023 TKAs and 247,112 (9.1%) revisions between 2005 and 2014. Cannabis use was prevalent in 18,875 (0.7%) of TKApatients with 2,419 (12.8%) revisions within the cannabis cohort. Revision incidence was significantly greater in patients who use cannabis (p < 0.001). Time to revision was also significantly decreased in patients who used cannabis, with increased 30- and 90-day revision incidence compared to the noncannabis group (P < 0.001). Infection was the most common cause of revision in both groups (33.5% nonusers versus 36.6% cannabis users). Cannabis use may result in decreasing implant survivorship and increasing the risk for revision within the 90-day global period compared to noncannabis users following primary TKA.

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

➢ Implementation of multimodal pain management regimens after total knee arthroplasty has increased patient satisfaction, decreased pain scores, and facilitated faster recovery.➢ A variety of oral and intravenous analgesics, including nonsteroidal anti-inflammatory drugs, gabapentinoids, acetaminophen, and opioids, can be employed preoperatively and postoperatively.➢ Neuraxial anesthesia, peripheral nerve blocks, and periarticular injections are effective pain modulators that should be implemented in concert with the anesthesia teams.➢ There is no consensus on the optimal multimodal pain regimen, and substantial variability exists between institutions and providers.➢ The goals of minimizing pain and improving functional recovery in the postoperative period must be considered in light of evidence-based practice as well as the risk profile of the proposed analgesic treatment.

Nutritional status has become increasingly important in optimizing surgical outcomes and preventing postoperative infection and wound complications. However, currently, there is a paucity in the orthopaedics literature investigating the relationship between nutritional status and wound complications following total knee arthroplasty (TKA). Therefore, the purpose of this study was to determine the prevalence of (1) postoperative infections, (2) wound complications, (3) concomitant infection with wound (CoIW) complication, and (4) infection followed by wound complication by using (1) albumin, (2) prealbumin, and (3) transferrin levels as indicators of nutritional status. These four different outcome measures were chosen as they are encountered commonly in daily clinical practice. A retrospective review of a national private payer database for patients who underwent TKA with postoperative infections and wound complications stratified by preoperative serum albumin (normal: 3.5–5 g/dL), prealbumin (normal: 16–35 mg/dL), and transferrin levels (normal: 200–360 mg/dL) between 2007 and 2015 was conducted. Patients were identified by Current Procedural Terminology (CPT), International Classification of Disease, ninth revision (ICD-9) codes, and Logical Observation Identifiers Names and Codes (LOINC). Linear regression was performed to evaluate changes over times. Yearly rates of infection, as well as a correlation and odds ratio analysis of nutritional laboratory values to postoperative complications, were also performed. Our query returned a total of 161,625 TKAs, of which 11,047 (7%) had postoperative wound complications, 18,403 (11%) had infections, 6,296 (34%) had CoIW, and 4,877 (4%) patients with infection developed wound complications. Albumin was the most commonly ordered laboratory test when assessing complications (96%). Wound complications, infections, CoIW, and infection with wound complications after were higher in those below the normal range: albumin <3.5 g/dL (9, 14, 6, and 5%), prealbumin <15 mg/dL (20, 23, 13, and 12%), and transferrin <200 mg/dL (12, 17, 6, and 6%). Preoperative albumin, prealbumin, and transferrin values falling below the normal range represented an increased risk for postoperative complications. Those patients who were in the normal range, however, did not have an increased risk. Therefore, our results suggest that preoperative nutritional optimization can play an important role in reducing the risk for postoperative complications.