{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:17:44Z","timestamp":1790619464383,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH-R41DA059303"],"award-info":[{"award-number":["NIH-R41DA059303"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam\u2122 introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur\u2122, which comprises a combination of liposomes and extended-release morphine, and Exparel\u2122, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef\u2122, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices\/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices\/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur\u2122, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel\u2122 is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel\u2122 is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel\u2122 is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef\u2122 is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices\/patches. Two studies support the use of nanocapacitor-based devices\/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo\u2122 pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device\/patches (NeuroCuple\u2122 device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple\u2122 devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur\u2122, bupivacaine Exparel\u2122 and a mixture of bupivacaine and meloxicam (Zynrelef\u2122) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices\/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple\u2122 device and the based Kailo\u2122 pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices\/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device\/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices\/patches.<\/jats:p>","DOI":"10.3390\/jcm13092611","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T10:33:36Z","timestamp":1714386816000},"page":"2611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nanotechnology for Pain Management"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-5482","authenticated-orcid":false,"given":"Jacques E.","family":"Chelly","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"},{"name":"Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv K.","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Kearns","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-0951","authenticated-orcid":false,"given":"Orkun","family":"Kopac","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-8313","authenticated-orcid":false,"given":"Senthilkumar","family":"Sadhasivam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1016\/j.arth.2017.08.010","article-title":"Opioid use following total hip arthroplasty: Trends and risk factors for prolonged use","volume":"32","author":"Bedard","year":"2017","journal-title":"J. Arthroplast."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1016\/j.arth.2017.03.014","article-title":"Opioid use after total knee arthroplasty: Trends and risk factors for prolonged use","volume":"32","author":"Bedard","year":"2017","journal-title":"J. Arthroplast."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e170504","DOI":"10.1001\/jamasurg.2017.0504","article-title":"New persistent opioid use after minor and major surgical procedures in US adults","volume":"152","author":"Brummett","year":"2017","journal-title":"JAMA Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/SLA.0000000000002308","article-title":"Probability of opioid prescription refilling after surgery: Does initial prescription dose matter?","volume":"268","author":"Sekhri","year":"2018","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1001\/jamainternmed.2016.3298","article-title":"Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period","volume":"176","author":"Sun","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353.e1","DOI":"10.1016\/j.ajog.2016.03.016","article-title":"Persistent opioid use following cesarean delivery: Patterns and predictors among opioid-naive women","volume":"215","author":"Bateman","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.mayocp.2015.04.012","article-title":"Incidence and risk factors for progression from short-term to episodic or long-term opioid prescribing: A population-based study","volume":"90","author":"Hooten","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.arth.2018.03.068","article-title":"Patient Factors Associated with Prolonged Postoperative Opioid Use After Total Knee Arthroplasty","volume":"33","author":"Namba","year":"2018","journal-title":"J. Arthroplasty"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jhsa.2016.07.113","article-title":"Risk of prolonged opioid use among opioid-na\u00efve patients following common hand surgery procedures","volume":"41","author":"Johnson","year":"2016","journal-title":"J. Hand Surg. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1001\/jamaoto.2017.0582","article-title":"Chronic opioid use following surgery for oral cavity cancer","volume":"143","author":"Pang","year":"2017","journal-title":"JAMA Otolaryngol. Head. Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/pds.3625","article-title":"Chronic opioid use emerging after bariatric surgery","volume":"23","author":"Raebel","year":"2014","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1213\/ANE.0b013e31825c049f","article-title":"A pilot cohort study of the determinants of longitudinal opioid use after surgery","volume":"115","author":"Carroll","year":"2012","journal-title":"Anesth. Analg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2106\/JBJS.L.01406","article-title":"Risk factors for continued opioid use one to two months after surgery for musculoskeletal trauma","volume":"96","author":"Helmerhorst","year":"2014","journal-title":"J. Bone Jt. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e010664","DOI":"10.1136\/bmjopen-2015-010664","article-title":"Risk factors for persistent and new chronic opioid use in patients undergoing total hip arthroplasty: A retrospective cohort study","volume":"6","author":"Inacio","year":"2016","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.2106\/JBJS.16.01075","article-title":"Risk factors for prolonged opioid use following spine surgery, and the association with surgical intensity, among opioid-naive patients","volume":"99","author":"Schoenfeld","year":"2017","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Singh, J.A., and Lewallen, D. (2010). Predictors of pain and use of pain medications following primary Total Hip Arthroplasty (THA): 5,707 THAs at 2-years and 3,289 THAs at 5-years. BMC Musculoskelet. Disord., 11.","DOI":"10.1186\/1471-2474-11-90"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R248","DOI":"10.1186\/ar4091","article-title":"Predictors of use of pain medications for persistent knee pain after primary Total Knee Arthroplasty: A cohort study using an institutional joint registry","volume":"14","author":"Singh","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.arth.2016.09.040","article-title":"Chronic use of opioids before and after total knee arthroplasty: A retrospective cohort study","volume":"32","author":"Hansen","year":"2017","journal-title":"J. Arthroplast."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"g1251","DOI":"10.1136\/bmj.g1251","article-title":"Rates and risk factors for prolonged opioid use after major surgery: Population based cohort study","volume":"348","author":"Clarke","year":"2014","journal-title":"Bri. Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1007\/s00464-018-6078-3","article-title":"What factors are associated with increased risk for prolonged postoperative opioid usage after colorectal surgery?","volume":"32","author":"Stafford","year":"2018","journal-title":"Surg. Endosc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"355e","DOI":"10.1097\/01.prs.0000475788.52446.7b","article-title":"The utilization of opioid analgesics following common upper extremity surgical procedures: A national, population-based study","volume":"137","author":"Waljee","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.2106\/JBJS.L.00619","article-title":"Rates of prescription opiate use before and after injury in patients with orthopaedic trauma and the risk factors for prolonged opiate use","volume":"95","author":"Holman","year":"2013","journal-title":"J. Bone Jt. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.arthro.2017.12.005","article-title":"Prospective, Observational Study of Opioid Use After Hip Arthroscopy for Femoroacetabular Impingement Syndrome","volume":"34","author":"Cunningham","year":"2018","journal-title":"Arthroscopy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1097\/j.pain.0000000000000516","article-title":"Trends and predictors of opioid use following total knee and total hip arthroplasty","volume":"157","author":"Goesling","year":"2016","journal-title":"Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.2217\/pmt-2016-0004","article-title":"Chronic postsurgical pain and persistent opioid use following surgery: The need for a transitional pain service","volume":"6","author":"Huang","year":"2016","journal-title":"Pain Manag."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1200\/JCO.2017.74.1363","article-title":"New persistent opioid use among patients with cancer after curative-intent surgery","volume":"35","author":"Lee","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/0194599818778276","article-title":"Persistent Postoperative Opioid Use in Older Head and Neck Cancer Patients","volume":"160","author":"Saraswathula","year":"2018","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1001\/jamainternmed.2018.5419","article-title":"Association of Opioid Prescriptions From Dental Clinicians for US Adolescents and Young Adults With Subsequent Opioid Use and Abuse","volume":"179","author":"Schroeder","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/archinternmed.2011.1827","article-title":"Long-term analgesic use after low-risk surgery: A retrospective cohort study","volume":"172","author":"Alam","year":"2012","journal-title":"Arch. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.joca.2017.04.002","article-title":"Patterns and predictors of persistent opioid use following hip or knee arthroplasty","volume":"25","author":"Kim","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/ctr.12414","article-title":"Chronic opioid analgesic usage post-kidney transplantation and clinical outcomes","volume":"28","author":"Kulshrestha","year":"2014","journal-title":"Clin. Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1001\/jamasurg.2016.1681","article-title":"Risks of developing persistent opioid use after major surgery","volume":"151","author":"Soneji","year":"2016","journal-title":"JAMA Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1213\/ANE.0000000000001943","article-title":"Lack of association between the use of nerve blockade and the risk of postoperative chronic pioid use among patients undergoing total knee arthroplasty: Evidence from the Marketscan Database","volume":"125","author":"Sun","year":"2017","journal-title":"Anesth. Analg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1373\/clinchem.2016.264986","article-title":"Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice","volume":"63","author":"Matic","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1093\/pm\/pnac056","article-title":"Acupuncture Therapy as an Evidence-Based Nonpharmacologic Strategy for Comprehensive Acute Pain Care: The Academic Consortium Pain Task Force White Paper Update","volume":"23","author":"Nielsen","year":"2022","journal-title":"Pain Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/pme.12685","article-title":"Acupuncture Provides Short-term Pain Relief for Patients in a Total Joint Replacement Program","volume":"16","author":"Crespin","year":"2015","journal-title":"Pain Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e89277","DOI":"10.5812\/aapm.89277","article-title":"Hypnosis as an Approach to Control Pain and Anxiety in Anterior Cruciate Ligament Reconstruction and Meniscal Surgeries: Two Case Presentations","volume":"9","author":"Fathi","year":"2019","journal-title":"Anesth. Pain Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e051073","DOI":"10.1136\/bmjopen-2021-051073","article-title":"Efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: A systematic review and meta-analysis of 381 studies (the meta-TENS study)","volume":"12","author":"Johnson","year":"2022","journal-title":"BMJ Open"},{"key":"ref_39","first-page":"CD011890","article-title":"Cochrane Pain, Palliative and Supportive Care Group. Transcutaneous electrical nerve stimulation (TENS) for chronic pain\u2013an overview of Cochrane Reviews","volume":"2019","author":"Gibson","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chelly, J.E., Orebaugh, S.L., Rodosky, M.W., Groff, Y.J., Norton, B.E., Monroe, A.L., Alimi, D., Sadhasivam, S.K., and Vogt, K.M. (2022). The Effect of Cryo-auriculotherapy on Post-Operative Pain Management following Rotator Cuff Surgery: A Randomized, Placebo-Controlled Study. medRxiv.","DOI":"10.1101\/2022.02.05.22270330"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1039\/C9BM00423H","article-title":"Recent advances in inorganic nanomaterials for wound-healing applications","volume":"7","author":"Nethi","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.addr.2018.03.005","article-title":"Nanopharmaceuticals for\u2013wound healing\u2014Lost in translation?","volume":"129","author":"Ashtikar","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1089\/wound.2019.1094","article-title":"Nanotechnology Approaches in Chronic Wound Healing","volume":"10","author":"Engel","year":"2021","journal-title":"Adv. Wound Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2174\/1381612828666220328121211","article-title":"Nanomaterials-based Drug Delivery Approaches for Wound Healing","volume":"28","author":"Girija","year":"2022","journal-title":"Curr. Pharm. Des."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1049\/iet-nbt.2018.5312","article-title":"Development of nanotechnology for advancement and application in wound healing: A review","volume":"13","author":"Bhattacharya","year":"2019","journal-title":"IET Nanobiotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.2174\/1381612823666170503152550","article-title":"Nanotechnology: A Promising Tool Towards Wound Healing","volume":"23","author":"Alberti","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1021\/nl102184c","article-title":"Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications","volume":"10","author":"Shi","year":"2010","journal-title":"Nano Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1007\/s11517-022-02664-3","article-title":"Nanotechnology and quantum science enabled advances in neurological medical applications: Diagnostics and treatments","volume":"60","author":"Batool","year":"2022","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1038\/s41467-022-29726-2","article-title":"Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes","volume":"13","author":"Jahed","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101223","DOI":"10.1016\/j.nantod.2021.101223","article-title":"Nanotechnology for Pain Management: Current and Future Therapeutic Interventions","volume":"39","author":"Bhansali","year":"2021","journal-title":"Nano Today"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jconrel.2016.05.044","article-title":"Nanoparticle-mediated brain drug delivery: Overcoming blood\u2013brain barrier to treat neurodegenerative diseases","volume":"235","author":"Saraiva","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.2147\/DDDT.S417051","article-title":"Recent Research Advances in Nano-Based Drug Delivery Systems for Local Anesthetics","volume":"17","author":"Ma","year":"2023","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/00000542-200505000-00022","article-title":"Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation","volume":"102","author":"Viscusi","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1213\/01.ANE.0000145009.03574.78","article-title":"A Comparison of Depodur\u2122, a Novel, Single-Dose Extended-Release Epidural Morphine, with Standard Epidural Morphine for Pain Relief After Lower Abdominal Surgery","volume":"100","author":"Gambling","year":"2005","journal-title":"Anesth. Analg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bpa.2019.03.002","article-title":"In search of the Holy Grail: Poisons and extended release local anesthetics","volume":"33","author":"Coppens","year":"2019","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11916-020-00905-4","article-title":"Exparel for Postoperative Pain Management: A Comprehensive Review","volume":"24","author":"Kaye","year":"2020","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.jss.2021.02.024","article-title":"The Efficacy of Liposomal Bupivacaine for Opioid and Pain Reduction: A Systematic Review of Randomized Clinical Trials","volume":"264","author":"Ji","year":"2021","journal-title":"J. Surg. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.arth.2022.03.073","article-title":"Liposomal Bupivacaine in Adductor Canal Blocks Before Total Knee Arthroplasty Leads to Improved Postoperative Outcomes: A Randomized Controlled Trial","volume":"37","author":"Malige","year":"2022","journal-title":"Arthroplasty"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/ALN.0000000000003651","article-title":"Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia","volume":"134","author":"Hussain","year":"2021","journal-title":"Anesthesiology"},{"key":"ref_60","unstructured":"(2024, March 30). Available online: https:\/\/www.zynrelef-accessdata.fda.gov\/."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1136\/rapm-2019-100531","article-title":"HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: Phase III results from the randomized EPOCH 1 study","volume":"44","author":"Viscusi","year":"2019","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/s10029-019-02023-6","article-title":"HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: Results from the phase 3 EPOCH 2 study","volume":"23","author":"Viscusi","year":"2019","journal-title":"Hernia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s40265-021-01551-9","article-title":"Bupivacaine\/Meloxicam Prolonged Release: A Review in Postoperative Pain","volume":"81","author":"Blair","year":"2021","journal-title":"Drugs"},{"key":"ref_64","first-page":"1000002","article-title":"Safety and efficacy of Zynrelef in Combination with a Single Unilateral or Bilateral Nerve Block Performed Prior to Surgery","volume":"12","author":"Goel","year":"2023","journal-title":"J. Pain Relief"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.33425\/2639-846X.1059","article-title":"Using A Novel, Non-Drug, Topical Pain-Relief Patch to Improve Pain and Function: Final Analysis of the PREVENT Study","volume":"6","author":"Gudin","year":"2022","journal-title":"Anesth. Pain Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chelly, J.E., Klatt, B.A., Groff, Y., O\u2019Malley, M., Lin, H.H.S., and Sadhasivam, S. (2023). Role of the NeuroCupleTM Device for the Postoperative Pain Management of Patients Undergoing Unilateral Primary Total Knee and Hip Arthroplasty: A Pilot Prospective, Randomized, Open-Label Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12237394"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gudmundsson, P., Nakonezny, P.A., Lin, J., Owhonda, R., Richard, H., and Wells, J. (2021). Functional improvement in hip pathology is related to improvement in anxiety, depression, and pain catastrophizing: An intricate link between physical and mental well-being. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04001-5"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1007\/s00167-015-3737-y","article-title":"The presence and influence of mild depressive symptoms on post-operative pain perception following primary total knee arthroplasty","volume":"25","author":"Bistolfi","year":"2017","journal-title":"Knee Surg. Sports Traum. Arth."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1186\/s13018-022-03288-x","article-title":"Sleep disturbance, dyspnea, and anxiety following total joint arthroplasty: An observational study","volume":"17","author":"George","year":"2022","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1302\/0301-620X.104B4.BJJ-2021-1089.R1","article-title":"PROMIS Depression and Anxiety in shoulder surgery patients","volume":"104","author":"Baker","year":"2022","journal-title":"Bone Jt. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1093\/pm\/pnab035","article-title":"Temporal Association of Pain Catastrophizing and Pain Severity Across the Perioperative Period: A Cross-Lagged Panel Analysis After Total Knee Arthroplasty","volume":"22","author":"Speed","year":"2021","journal-title":"Pain Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1037\/1040-3590.7.4.524","article-title":"The Pain Catastrophizing Scale: Development and validation","volume":"7","author":"Sullivan","year":"1995","journal-title":"Psychol. Assess"},{"key":"ref_73","first-page":"93","article-title":"The use of nanotechnology as an alternative to opioids for postoperative pain management following a TKA","volume":"13","author":"Chelly","year":"2023","journal-title":"J. Orthop. Case Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7086","DOI":"10.1136\/bmj.c7086","article-title":"Cardiovascular safety of non-steroidal anti-inflammatory drugs: Network meta-analysis","volume":"342","author":"Trelle","year":"2011","journal-title":"BMJ"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev.pa.33.040193.002251","article-title":"Renal toxicity of the nonsteroidal anti-inflammatory drugs","volume":"33","author":"Murray","year":"1993","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2106\/JBJS.H.00079","article-title":"Continuous psoas compartment block vs. continuous femoral block or PCA for total hip arthroplasty","volume":"1","author":"Marino","year":"2009","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1097\/JHQ.0000000000000322","article-title":"Preventing Postoperative Opioid-induced respiratory depression through Implementation of an Enhanced Monitoring Program","volume":"44","author":"Kozub","year":"2021","journal-title":"J. Healthc. Qual."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S2468-1253(18)30008-6","article-title":"Pathophysiology, diagnosis, and management of opioid-induced constipation","volume":"3","author":"Farmer","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1053\/j.gastro.2018.07.016","article-title":"American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation","volume":"156","author":"Crockett","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Leon, M.M., Mastaleru, A., Oancea, A., Alexa-Stratulat, T., Peptu, C.A., Tamba, B.-I., Harabagiu, V., Grosu, C., Alexa, A.I., and Cojocaru, E. (2024). Lidocaine\u2013Liposomes\u2014A Promising Frontier for Transdermal Pain Management. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010271"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1038\/srep01796","article-title":"An ab-initio computational method to determine dielectric properties of biological materials","volume":"3","author":"Abeyrathne","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0006-3495(76)85741-4","article-title":"Piezoelectric and related properties of hydrated collagen","volume":"16","author":"Fukada","year":"1976","journal-title":"Biophys. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ijengsci.2005.11.001","article-title":"Bioelectrodynamics in living organisms","volume":"44","author":"Zhou","year":"2006","journal-title":"Int. J. Eng. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"064301","DOI":"10.1103\/PhysRevB.74.064301","article-title":"Lattice dynamical and dielectric properties of L-amino acids","volume":"74","author":"Tulip","year":"2006","journal-title":"Phys. Rev. B"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0006-3495(75)85839-5","article-title":"Effect of water on piezoelectricity in bone and collagen","volume":"15","author":"Netto","year":"1975","journal-title":"Biophys. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/9\/2611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:36:11Z","timestamp":1760106971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/9\/2611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":85,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["jcm13092611"],"URL":"https:\/\/doi.org\/10.3390\/jcm13092611","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]}}}