Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

BACKGROUND: The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. RESULTS: At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. CONCLUSION: Cold allodynia and significant recovery from spared-nerve injury-induced mechanical hypersensitivity are two novel phenotypes which characterize the global CB1R-/- mice. An increase in transient receptor potential channel of melastatin 8 channel function in DRG neurons may underlie the cold phenotype. Recovery of mechanical thresholds in the CB1R knockouts was independent of motor function. These results indicate that CB1R expression contributes to the development of persistent mechanical hypersensitivity, protects against the development of robust cold allodynia but is not involved in motor impairment following spared-nerve injury in mice.

Cardiac Hemangioma: A Rare Tumor Presenting as Postpartum Chest Pain.

Pulmonary embolism, peripartum cardiomyopathy, acute myocardial infarction, aortic dissection, anxiety, and gastroesophageal reflux disease are known causes of chest pain during the peripartum period. A cardiac tumor is a rare cause of chest pain during this time period. While cardiac myxomas during pregnancy have been reported, cardiac hemangiomas are exceptionally rare. To the best of our knowledge, there are no existing case reports regarding cardiac hemangiomas in either pregnant or postpartum patients. Here, we present a 23-year-old female who presented with visual changes, headache, and midsternal pain and was subsequently found to have a cardiac hemangioma.

Successful Neuromuscular Blockade Reversal Using Sugammadex and Neostigmine Failed to Prevent Myasthenic Crisis After Emergency Surgery: A Case Report.

Recent literature suggests that the use of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) reduces the risk of postoperative myasthenic crisis (MC) in patients with myasthenia gravis (MG), particularly after thymectomy, but studies are lacking on emergency surgeries. We achieved successful intraoperative reversal of neuromuscular blockade (NMB) using a combination of sugammadex and neostigmine (with glycopyrrolate). However, MC was not avoided and reintubation was required on postoperative day 1. A 65-year-old male with a longstanding history of MG presented to the emergency department with complaints of abdominal pain, diarrhea, vomiting, chills, and fatigue for three days. A computed tomography (CT) scan of the abdomen showed acute appendicitis, for which he underwent a laparoscopic appendectomy on hospital day 1. The patient received successful general anesthesia with a rapid sequence induction using a smaller than average dose of rocuronium, given his history of MG. At the conclusion of the case, sugammadex followed by neostigmine/glycopyrrolate and a subsequent dose of sugammadex were given, with reversal of NMB. The patient was successfully extubated but required reintubation on postoperative day 1 for hypercapnic respiratory failure. Our case report on this patient with MG yields two topics that have not been extensively examined. First, dual therapy with sugammadex and neostigmine/glycopyrrolate may provide significant clinical benefit over individual therapy for NMBA reversal, given that their mechanisms of action are different and particularly when sugammadex is given prior to neostigmine/glycopyrrolate. Second, anesthesia literature is lacking on MG patients undergoing emergency surgeries. While sugammadex has been promising in medically optimized non-emergent surgeries, we discuss here a case where sugammadex failed to prevent MC in the emergency surgery setting and a look into what may provide patients with the best chance for avoiding postoperative MC.

The Use of Enhanced Recovery After Surgery Protocols and Sugammadex in a Friedreich Ataxia Patient Who Underwent Robotic Surgery: A Case Report of a Patient Who Required No Postoperative Opioids and Was Discharged Home Earlier Than Anticipated.

Robotic surgery has shown to have numerous benefits over traditional and laparoscopic surgery, namely, superior precision and improved recovery with shorter hospital stays. However, robotic surgery also presents several issues, including hemodynamic changes related to positioning and the use of pneumoperitoneum. These matters can be problematic in patients with neuromuscular conditions such as Friedreich ataxia (FRDA). Due to a baseline weakened musculature and a higher prevalence of cardiac disease and scoliosis, patients with FRDA may not be as likely to tolerate the cardiopulmonary physiologic changes associated with robotic surgery. Additionally, positioning for robotic surgery can be challenging in FRDA patients who have progressed to spasticity and contractures. To the best of our knowledge, there are no case reports of approaches specifically discussing anesthesia management for robotic surgery in the FRDA patient population. Anesthesia in general must be carefully planned in FRDA patients to allow for the best possible recovery and minimize complications. Due to the underlying neuromuscular compromise seen in these patients, their ability to recover from the pharmacologic and physiologic changes associated with anesthesia can be more difficult. They are prone to sensitivity to opioids, sedatives, and neuromuscular blocking agents (NMBAs) and are less likely to tolerate hemodynamic changes. Our review revealed no literature to suggest the routine use of Enhanced Recovery After Surgery (ERAS) protocols in FRDA patients or in patients with neuromuscular disease in general. The use of sugammadex has also been shown to be safe, and literature suggests superiority in both the general population and those with neuromuscular conditions. Our understanding is that there is very limited literature in regard to the safe use of sugammadex in FRDA patients.