{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T04:49:27Z","timestamp":1772081367257,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"9-10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The prevalence of chronic pain of service members (SMs) in the U.S. is estimated to be higher (roughly 31-44%) compared to that of civilian population (26%). This higher prevalence is likely due to the high physical demands related combat and training injuries that are not immediately resolved and worsen over time. Mental Health America reports that chronic pain can lead to other mental health conditions such as severe anxiety, depression, bipolar disorder, and post-traumatic stress disorder. Such mental health conditions can negatively affect job performance, reduce readiness for military duties, and often lead to patterns of misuse of opioid after SMs entering civilian life. The primary objective of this narrative review is to present a summarized guideline for the treatment of two types of pain that likely affect SMs, namely nociceptive somatic pain and neuropathic pain. This review focused on a stepwise approach starting with nonopioid interventions prior to opioid therapy. The secondary objective of this review is to elucidate the primary mechanisms of action and pathways associated with these two types of pain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We followed the Scale for Assessment of Narrative Review Articles when transcribing this narrative review article to enhance the quality and brevity of this review. This Scale has 0.77% an intra-class coefficient of correlation, 95% confidence interval and 0.88 inter-rater reliability. We searched PubMed, Google Scholar, WorldCAT, and the Cochrane Library for the primary and secondary articles that targeted mechanisms of action, pathways, and pharmacological modalities for nociceptive somatic and neuropathic pain that were published from 2011 to 2022. We excluded articles related to pediatric, some specific pain conditions such as cancer-related pain, palliative care, end-of-life care, and articles that were not written in English language. For pharmacologic selection, we adopted the guidelines from the Policy for Implementation of a Comprehensive Policy on Pain Management by the Military Health Care system for the Fiscal Year 2021; the Clinical Practice Guidance for Opioid Therapy for Chronic Pain by the Department of Defense\/Veterans Health Administration (2022); the (2021) Implementation of a Comprehensive Policy on Pain Management by the Military Health Care System; and the (2022) Guideline for Prescribing Opioids for Chronic Pain<\/jats:p>\n                  <jats:p>by the Centers for Disease Control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>From the knowledge of the mechanisms of action and pathways, we can be more likely to identify the causative origins of pain. As a result, we can correctly diagnose the type of pain, properly develop an efficient and personalized treatment plan, minimize adverse effects, and optimize clinical outcomes. The guideline, however, does not serve as a substitute for clinical judgment in patient-centered decision-making. Medication choices should be individualized judiciously based on the patient\u2019s comorbid conditions, available social and economic resources, and the patient\u2019s preferences to balance the benefits and risks associated with various pain medications and to achieve optimal pain relief and improve the patient\u2019s quality of life.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/milmed\/usad506","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T15:22:24Z","timestamp":1706800944000},"page":"e1879-e1889","source":"Crossref","is-referenced-by-count":5,"title":["A Pathophysiological Approach for Selecting Medications to Treat Nociceptive and Neuropathic Pain in Servicemembers"],"prefix":"10.1093","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-4401","authenticated-orcid":false,"given":"Khan Thi","family":"Nguyen","sequence":"first","affiliation":[{"name":"Interdisciplinary Pain Management Clinic, William Beaumont Army Medical Center , Fort Bliss, TX 79918, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel W","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Interdisciplinary Pain Management Clinic, William Beaumont Army Medical Center , Fort Bliss, TX 79918, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reginald B","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"Department of Clinical Investigation, William Beaumont Army Medical Center , Fort Bliss, TX 79918, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"issue":"9-10","key":"2024083012291494500_R1","doi-asserted-by":"publisher","first-page":"e330","DOI":"10.1093\/milmed\/usx200","article-title":"Prevalence of pain diagnoses and burden of pain among active-duty soldiers, FY2012","volume":"183","author":"Reif","year":"2018","journal-title":"Mil Med"},{"issue":"6","key":"2024083012291494500_R2","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.pain.2010.12.036","article-title":"A population-based survey of chronic pain and its treatment with prescription drugs","volume":"152","author":"Toblin","year":"2011","journal-title":"Pain"},{"issue":"5","key":"2024083012291494500_R3","doi-asserted-by":"crossref","first-page":"E429","DOI":"10.36076\/ppj.2020\/23\/E429","article-title":"A burden and prevalence analysis of chronic pain by distinct case definitions among active-duty U.S. military service members, 2018","volume":"23","author":"Smith","year":"2020","journal-title":"Pain Physician"},{"issue":"3","key":"2024083012291494500_R4","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare4030038","article-title":"Military chronic musculoskeletal pain and psychiatric comorbidity: is better pain management the answer?","volume":"4","author":"McGeary","year":"2016","journal-title":"Healthcare (Basel)"},{"key":"2024083012291494500_R5","first-page":"3","volume-title":"Pain Syndromes\u2013From Recruitment to Returning","author":"Bray","year":"2012"},{"issue":"4","key":"2024083012291494500_R6","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/ajad.13027","article-title":"Brief report: opioid-involved overdose mortality in United States veterans","volume":"29","author":"Peltzman","year":"2020","journal-title":"Am J Addict"},{"issue":"1","key":"2024083012291494500_R7","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1080\/07853890.2022.2092896","article-title":"U.S. Military veterans and the opioid overdose crisis: a review of risk factors and prevention efforts","volume":"54","author":"Bennett","year":"2022","journal-title":"Ann Med"},{"issue":"5","key":"2024083012291494500_R8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1155\/2011\/465281","article-title":"A comparison between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain","volume":"16","author":"Furlan","year":"2011","journal-title":"Pain Res Manag"},{"issue":"4","key":"2024083012291494500_R9","doi-asserted-by":"publisher","first-page":"276","DOI":"10.7326\/M14-2559","article-title":"The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop","volume":"162","author":"Chou","year":"2015","journal-title":"Ann Intern Med"},{"key":"2024083012291494500_R10","article-title":"VHA DIRECTIVE 2009-053","author":"Department of Veterans Affairs - Veterans Health Administration Washington, DC 20420"},{"key":"2024083012291494500_R11","article-title":"Policy for Comprehensive Pain Management (Health Affairs Policy 11-003)","author":"Department of Defense","year":"2011"},{"issue":"1","key":"2024083012291494500_R12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1037\/hea0000245","article-title":"The bidirectional relationship between sleep complaints and pain: analysis of data from a randomized trial","volume":"35","author":"Koffel","year":"2016","journal-title":"Health Psychol"},{"key":"2024083012291494500_R13","article-title":"Policy for Implementation of a Comprehensive Policy on Pain Management by the Military Health Care system for FY for Fiscal Year (FY) 2021","volume-title":"Office of the Army Surgeon General","author":"Department\u2019s Department of Defense (2021)","year":"2021"},{"key":"2024083012291494500_R14","author":"VA\/DoD Clinical Practice Guidelines for Opioid Therapy for Chronic Pain","year":"2022"},{"key":"2024083012291494500_R15","article-title":"Clinical Practice Guideline for Prescribing Opioids for Pain","author":"Centers for Disease Control and Prevention","year":"2022"},{"issue":"1","key":"2024083012291494500_R16","doi-asserted-by":"publisher","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA-a scale for the quality assessment of narrative review articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res Integr Peer Rev"},{"issue":"11","key":"2024083012291494500_R17","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1172\/JCI42843","article-title":"Nociceptors: the sensors of the pain pathway","volume":"120","author":"Dubin","year":"2010","journal-title":"J Clin Invest"},{"issue":"2","key":"2024083012291494500_R18","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s00415-017-8641-6","article-title":"Advances in understanding nociception and neuropathic pain","volume":"265","author":"Smith","year":"2018","journal-title":"J Neurol"},{"issue":"11","key":"2024083012291494500_R19","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/nm.2235","article-title":"Nociceptor sensitization in pain pathogenesis","volume":"16","author":"Gold","year":"2010","journal-title":"Nat Med"},{"issue":"8","key":"2024083012291494500_R20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082164","article-title":"General pathways of pain sensation and the major neurotransmitters involved in pain regulation","volume":"19","author":"Yam","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"5","key":"2024083012291494500_R21","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"2024083012291494500_R22","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1007\/s00702-014-1180-8","article-title":"Glutamate as a neurotransmitter in the healthy brain","volume":"121","author":"Zhou","year":"2014","journal-title":"J Neural Transm (Vienna)"},{"key":"2024083012291494500_R23","volume-title":"Biochemistry, Substance P","author":"Graefe","year":"2022"},{"issue":"2","key":"2024083012291494500_R24","doi-asserted-by":"publisher","first-page":"ENEURO.0129","DOI":"10.1523\/ENEURO.0129-16.2017","article-title":"Divergent modulation of nociception by glutamatergic and GABAergic neuronal subpopulations in the periaqueductal gray","volume":"4","author":"Samineni","year":"2017","journal-title":"eNeuro"},{"issue":"11","key":"2024083012291494500_R25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112483","article-title":"Analgesic mechanisms of antidepressants for neuropathic pain","volume":"18","author":"Obata","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2024083012291494500_R26","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1152\/physrev.00045.2019","article-title":"Neuropathic pain: from mechanisms to treatment","volume":"101","author":"Finnerup","year":"2021","journal-title":"Physiol Rev"},{"issue":"1","key":"2024083012291494500_R27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1097\/00000542-200107000-00034","article-title":"Mechanism-based pain diagnosis: issues for analgesic drug development","volume":"95","author":"Woolf","year":"2001","journal-title":"Anesthesiology"},{"issue":"8","key":"2024083012291494500_R28","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1080\/14656566.2020.1735353","article-title":"Current, and future pharmacological agents for the treatment of back pain","volume":"21","author":"Bhatia","year":"2020","journal-title":"Expert Opin Pharmacother"},{"key":"2024083012291494500_R29","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101774","article-title":"Silencing COX-2 blocks PDK1\/TRAF4-induced AKT activation to inhibit fibrogenesis during skeletal muscle atrophy","volume":"38","author":"Chen","year":"2021","journal-title":"Redox Biol"},{"issue":"1","key":"2024083012291494500_R30","doi-asserted-by":"publisher","first-page":"143","DOI":"10.14336\/AD.2017.0306","article-title":"A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly","volume":"9","author":"Wongrakpanich","year":"2018","journal-title":"Aging Dis"},{"issue":"5","key":"2024083012291494500_R31","doi-asserted-by":"publisher","first-page":"384","DOI":"10.4097\/kja.20357","article-title":"Topical agents: a thoughtful choice for multimodal analgesia","volume":"73","author":"Choi","year":"2020","journal-title":"Korean J Anesthesiol"},{"issue":"4","key":"2024083012291494500_R32","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007400.pub3","article-title":"Topical NSAIDs for chronic musculoskeletal pain in adults","volume":"4","author":"Derry","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"2024083012291494500_R33","doi-asserted-by":"publisher","first-page":"4091","DOI":"10.2147\/DDDT.S328228","article-title":"Topical lidocaine for chronic pain treatment","volume":"15","author":"Voute","year":"2021","journal-title":"Drug Des Devel Ther"},{"issue":"7446","key":"2024083012291494500_R34","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38042.506748.EE","article-title":"Systematic review of topical capsaicin for the treatment of chronic pain","volume":"328","author":"Mason","year":"2004","journal-title":"BMJ"},{"issue":"23","key":"2024083012291494500_R35","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1001\/jama.2018","article-title":"Opioids for chronic noncancer pain: a systematic review and meta-analysis","volume":"320","author":"Busse","year":"2018","journal-title":"JAMA"},{"issue":"14","key":"2024083012291494500_R36","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1007\/s40265-020-01369-x","article-title":"The expanding role of the COX inhibitor\/opioid receptor agonist combination in the management of pain","volume":"80","author":"Varrassi","year":"2020","journal-title":"Drugs"},{"issue":"feb05 6","key":"2024083012291494500_R37","doi-asserted-by":"publisher","DOI":"10.1136\/bmj","article-title":"Neuropathic pain: mechanisms and their clinical implications","volume":"348","author":"Cohen","year":"2014","journal-title":"BMJ"},{"key":"2024083012291494500_R38","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.2147\/JPR.S246503","article-title":"Reducing opioid prescriptions by identifying responders on topical analgesic treatment using an individualized medicine and predictive analytics approach","volume":"13","author":"Gudin","year":"2020","journal-title":"J Pain Res"},{"key":"2024083012291494500_R39","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.2147\/JPR.S143513","article-title":"Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational optimizing patient experience and response to topical analgesics study","volume":"10","author":"Gudin","year":"2017","journal-title":"J Pain Res"},{"issue":"Suppl 1","key":"2024083012291494500_R40","doi-asserted-by":"publisher","first-page":"S23","DOI":"10.1097\/j.pain.0000000000001522","article-title":"Translational neuropathic pain research","volume":"160","author":"Attal","year":"2019","journal-title":"Pain"},{"issue":"Suppl 1","key":"2024083012291494500_R41","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1093\/pm\/pnz075","article-title":"A comprehensive algorithm for management of neuropathic pain [published correction appears in Pain Med","volume":"20","author":"Bates","year":"2019","journal-title":"Pain Med"},{"issue":"11","key":"2024083012291494500_R42","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD010567.pub2","article-title":"Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews","volume":"2013","author":"Wiffen","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"6","key":"2024083012291494500_R43","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007938.pub4","article-title":"Gabapentin for chronic neuropathic pain in adults","volume":"6","author":"Wiffen","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"2024083012291494500_R44","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007076.pub3","article-title":"Pregabalin for neuropathic pain in adults","volume":"1","author":"Derry","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"2024083012291494500_R45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3344\/kjp.2011.24.1.1","article-title":"Application of botulinum toxin in pain management","volume":"24","author":"Sim","year":"2011","journal-title":"Korean J Pain"},{"key":"2024083012291494500_R46","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00716","article-title":"Botulinum neurotoxin for the treatment of neuropathic pain","volume":"11","author":"Egeo","year":"2020","journal-title":"Front Neurol"},{"issue":"9","key":"2024083012291494500_R47","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9090260","article-title":"Botulinum toxin for the treatment of neuropathic pain","volume":"9","author":"Park","year":"2017","journal-title":"Toxins"},{"key":"2024083012291494500_R48","article-title":"Clinical Practice Guidelines We Can Trust","author":"Institute of Medicine (US) Committee on Standards for Developing Trustworthy Clinical Practice Guidelines"}],"container-title":["Military Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/189\/9-10\/e1879\/58971027\/usad506.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/189\/9-10\/e1879\/58971027\/usad506.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T13:40:04Z","timestamp":1725025204000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/milmed\/article\/189\/9-10\/e1879\/7595833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":48,"journal-issue":{"issue":"9-10","published-online":{"date-parts":[[2024,1,31]]},"published-print":{"date-parts":[[2024,8,30]]}},"URL":"https:\/\/doi.org\/10.1093\/milmed\/usad506","relation":{},"ISSN":["0026-4075","1930-613X"],"issn-type":[{"value":"0026-4075","type":"print"},{"value":"1930-613X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,9]]},"published":{"date-parts":[[2024,1,31]]}}}