Pharmacology/Drug Development

Burn injury in children can cause severe and chronic physical and mental sequelae. Opioids are a mainstay in burn pain management but increasing utilization in this country has led to concern for their continued use and potential for dependence. Methadone is a long-acting analgesic that targets the N-methyl-D-aspartate (NMDA) receptor in addition to the mu opioid receptor and has benefit in adult burn patients. However, its use in the pediatric burn population has been less robustly studied. This is a retrospective cohort study at a single Level 1 Burn Center whose primary aim is to compare opioid utilization 36 hours postoperatively between pediatric burn patients who received intraoperative, intravenous methadone and those who did not. Secondary aim was to describe differences in methadone-related complications between the cohorts. There was decreased opioid utilization measured by median morphine equivalents per kilogram (ME/kg) postoperatively in the methadone cohort compared to the control cohort (0.54mg/kg v. 0.77mg/kg, p = 0.18). No adverse events were noted upon chart review. The data suggests methadone use is beneficial in pediatric burn patients, but further prospective studies are warranted on a larger population.

Osteoarthritis is a degenerative disease of the knee that affects 250 million people worldwide. Due to the rising incidence of knee replacement and revision surgery, there is a need for a nonsurgical treatment to reduce pain and improve function in patients with knee osteoarthritis. Placental-derived allografts, such as an amniotic suspension allograft (ASA), provide growth factors and cytokines that could potentially modulate the inflammatory environment of osteoarthritis. The purpose of this study was to evaluate the efficacy of ASA in a rat medial meniscal tear (MMT) induced osteoarthritis model through histology, microCT, synovial fluid biomarkers, and behavioral testing.

Oxaliplatin-induced peripheral neuropathy (OIPN) is an unwanted side effect of oxaliplatin chemotherapy treatment. OIPN manifests in an acute phase that lasts a few days after injection and a persistent phase that may become chronic. Currently, there is no consensus about a clinically applicable, quantitative, and objective measure of OIPN.

Among different types of chronic pain, neuropathic pain (NP), arising from damage to the nervous system, including peripheral fibers and central neurons, is notoriously difficult to treat and affects 7-10% of the general population. Currently available treatment options for NP are limited and opioid analgesics have severe side effects and can result in opioid use disorder. Recent studies have exhibited the role of dietary bioactive compounds in the mitigation of NP. Here, we assessed the effects of commonly consumed bioactive compounds (ginger, curcumin, omega-3 polyunsaturated fatty acids, epigallocatechin gallate, resveratrol, soy isoflavones, lycopene, and naringin) on NP and NP-related neuroinflammation. Cellular studies demonstrated that these bioactive compounds reduce inflammation via suppression of NF-κB and MAPK signaling pathways that regulate apoptosis/cell survival, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that these regularly consumed bioactive compounds have a pronounced anti-NP effect as shown by decreased mechanical allodynia, mechanical hyperalgesia, thermal hyperalgesia, and cold hyperalgesia. The proposed molecular mechanisms include (i) the enhancement of neuron survival, (ii) the reduction of neuronal hyperexcitability by activation of antinociceptive cannabinoid 1 receptors and opioid receptors, (iii) the suppression of sodium channel current, and (iv) enhancing a potassium outward current in NP-affected animals, triggering a cascade of chemical changes within and between neurons for pain relief. Human studies administered in this area have been limited. Future randomized controlled trials are warranted to confirm the findings of preclinical efficacies using bioactive compounds in patients with NP.

To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP).

Emergency or postoperative pain often represents an authentic challenge in patients who were already on opioid treatment for chronic pain. Thus, their management requires not only the physician's ability to treat acute pain, but also competence in switching the opioid that lost efficacy. Different aspects should be considered, such as opioids titration, switching, association and equianalgesia. The objective of this paper is to provide a narrative review, which has been elaborated and discussed among clinicians through an iterative process involving development and review of the draft during two web-based meetings and via email. This expert opinion aims to facilitate the correct opioid use through appropriate practices with a focus on pain treatment in emergency and postoperative pain. Equianalgesia tables were reviewed and integrated by clinicians and researchers with expertise in anesthesia, postoperative medicine, intensive care, emergency medicine pharmacology and addiction medicine. Special populations (liver/kidney failure, elder, pediatric, pregnancy/lactation) are discussed in detail along with other critical scenarios, such as: (i) rapid pain worsening in chronic pain (aggravating pain due to disease progression or tolerance development to analgesic therapy); (ii) acute pain on maintenance treatment; and (iii) pain management of complicated patients in emergency care. Extended and updated equianalgesia tables and conversion rates for 17 different opioid formulations (of 9 different molecules) are presented as follows. Opioids remain the class that best suits clinical needs of emergency and post-operative medicine. However, it should be stressed that equianalgesia can be affected by drug-to-drug interactions and pharmacological imprecision, in a complex field where clinical experience may be the main guiding principle.

Regenerative medicine interventions are applied to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous/allogenic biologics and it continues to expand. The anti-inflammatory, immunomodulatory, and regenerative properties of bone marrow mesenchymal stem cells (BM-MSCs), and investigation into their therapeutic efficacy and safety in patients with severe chronic low back pain, have not been demonstrated in controlled studies. Multiple pain generators have been hypothesized to be responsible in severe spinal degeneration and it is difficult to identify a single pain generator; consequently, resulting in inadequate therapeutic results.