Acute flare-ups of musculoskeletal conditions (i.e., post-operative hyperalgesia, osteoarthritis, occipital neuralgia, and lower back pain) present as increased intensity of pain. Currently, opioids are prescribed to treat these flare- ups, making musculoskeletal pain one of the most frequent reasons for opioid prescriptions. Overdoses, abuses, diversions, and deaths from prescription opioids have reached epidemic proportions in the United States with associated healthcare costs of over $700 billion. Our long-term objective is to develop alternative, non-addictive interventions to treat flare-ups of musculoskeletal conditions. Our proposed research aims to develop injectable long-acting anesthetic formulations by combining local anesthetics with low doses of anti-inflammatory/analgesic pain modulators and sustained delivery of these drugs using engineered carriers. Preliminary studies showed the potential of synergistic drug combinations in conjunction with injectable hydrogel/lipid nanocapsule nanocomposites in prolonging local analgesia. We propose to evaluate clinically used corticosteroids as well as emerging analgesic pain modulators in conjunction with ropivacaine to identify the synergistic drug combinations. A diffusion- and degradation-controlled release process will be investigated for the sustained delivery of the analgesic pain modulators to prevent perineural inflammation and neurotoxicity. The in vivo assessment of the efficacy and safety of the formulations will be performed by following the behavioral and electrophysiological responses in rat models. An injectable long-acting formulation, which can be administered in an outpatient facility and can sustain local hypoalgesic effects for 7-14 days, would significantly enhance the quality of life for those suffering from flare-ups without the dire consequences of opioid therapy.
Prescription opioids have reached epidemic proportions in the United States and musculoskeletal pain is one of the most frequent reasons for opioid prescription. With more than 100 million Americans suffering from musculoskeletal pain, there is an urgent need to find safe, effective and non-addictive interventions to manage musculoskeletal pain. The purpose of this application is to develop a novel injectable anesthetic formulation that can provide pain relief for up to 7-14 days with minimum side effects.
