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Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

ABSTRACT: Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo. A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7?days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain. STATEMENT OF SIGNIFICANCE:Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model.

SUBMITTER: Khanal M

PROVIDER: S-EPMC6020057 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

Khanal Manakamana M Gohil Shalini V SV Kuyinu Emmanuel E Kan Ho-Man HM Knight Brittany E BE Baumbauer Kyle M KM Lo Kevin W-H KW Walker Joseph J Laurencin Cato T CT Nair Lakshmi S LS

Acta biomaterialia 20180525

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadva ...[more]

PMID: 29803784

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Project description:Neuropathic pain (NP) can be challenging to treat effectively as analgesic pharmacotherapy (MED) can reduce pain, but the majority of patients do not experience complete pain relief. Our pilot approach is to assess the feasibility and efficacy of an evidence-based photobiomodulation (PBM) intervention protocol. This would be as an alternative to paralleled standard analgesic MED for modulating NP intensity-related physical function and quality of life (QoL) prospectively in a mixed neurological primary burning mouth syndrome and oral iatrogenic neuropathy study population (n = 28). The study group assignments and outcome evaluation strategy/location depended on the individual patient preferences and convenience rather than on randomisation. Our prospective parallel study aimed to evaluate the possible pre/post-benefit of PBM and to allow for a first qualitative comparison with MED, various patient-reported outcome measures (PROMs) based on Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT-II) were used for up to a nine-month follow-up period in both intervention groups (PBM and MED). The PBM protocol applied to the PBM group was as follows: λ810 nm, 200 mW, 0.088 cm2, 30 s/point, 9 trigger and affected points, twice a week for five consecutive weeks, whereas the MED protocol followed the National Institute of Clinical Excellence (NICE) guidelines. Our results showed that despite the severe and persistent nature of the symptoms of 57.50 ± 47.93 months at baseline in the PBM group, a notably rapid reduction in PISmax on VAS from 7.6 at baseline (T0) to 3.9 at one-month post-treatment (T3) could be achieved. On the other hand, mean PISmax was only reduced from 8.2 at baseline to 6.8 at T3 in the MED group. Our positive PBM findings furthermore support more patients' benefits in improving QoL and functional activities, which were considerably impaired by NP such as: eating, drinking and tasting, whereas the analgesic medication regimens did not. No adverse events were observed in both groups. To the best knowledge of the authors, our study is the first to investigate PBM efficacy as a monotherapy compared to the gold standard analgesic pharmacotherapy. Our positive data proves statistically significant improvements in patient self-reported NP, functionality, psychological profile and QoL at mid- and end-treatment, as well as throughout the follow-up time points (one, three, six and nine months) and sustained up to nine months in the PBM group, compared to the MED group. Our study, for the first time, proves the efficacy and safety of PBM as a potent analgesic in oral NP and as a valid alternative to the gold standard pharmacotherapy approach. Furthermore, we observed long-term pain relief and functional benefits that indicate that PBM modulates NP pathology in a pro-regenerative manner, presumably via antioxidant mechanisms.

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Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

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Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

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