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\n[https://doi.org/10.1007/s40263-025-01234-z](https://doi.org/10.1007/s40263-025-01234-z)  \nManaging Chronic Pain: The Ketamine Option  \nGisèle Pickering1,2,3 · Véronique Morel1,2 · Marion Voute1,2  \nReceived: 23 June 2025 / Accepted: 9 September 2025 / Published online: 16 October 2025 © The Author(s) 2025  \nAbstract  \nKetamine, an anaesthetic and sedative drug, has emerged as a promising therapeutic option for the management of chronic refractory pain, but is used off-label in this indication and known for its psychomimetic side-effects. The primary objective of this manuscript is to synthesize the current evidence on ketamine efficacy and safety for chronic refractory pain. Furthermore, it aims to identify critical knowledge gaps and propose a framework for its rational and safe clinical application. This narrative review analyses key findings from randomised and non-randomised clinical trials investigating ketamine’suse in chronic pain conditions. It also examines existing clinical guidelines and expert consensus statements to reach a comprehensive clinical perspective. Current evidence demonstrates that ketamine can provide significant short-term analgesia, especially in neuropathic pain, and is fairly well-tolerated in patients with severe refractory pain. However, long-term data on efficacy, cognitive impact, addiction risk and optimal dosing are severely lacking. The intravenous route remains the most studied, while alternatives are still underexplored. Ketamine is not a first-line treatment for pain and must be prescribed and supervised by trained specialists within a structured standard of care. Its future role in pain management hinges on collaborative translational research to define optimal administration routes, establish phenotyping strategies (on the basis of pain type, comorbidities and comedication), and conduct long-term studies assessing mood, quality of life and cognitive function to ensure both efficacy and safety.  \n1 Introduction  \n1.1 Chronic Pain  \nChronic pain management remains one of the most complex challenges in healthcare, often requiring a multimodal approach that combines pharmacological, psychotherapeutic and physical rehabilitation interventions [1, 2] . Chronic pain, defined as pain that persists or recurs for longer than 3 months [3], affects 20% of the population worldwide. It is a multifaceted condition, generally  \n* Gisèle Pickering [gisele.pickering@uca.fr](gisele.pickering@uca.fr)  \n1 Centre Hospitalier Universitaire de Clermont-Ferrand, Inserm CIC 1405, Plateforme d’Investigation Clinique,  \n63000 Clermont-Ferrand, France  \n2 Université Clermont Auvergne, Inserm 1107, Neuro-Dol, 63000 Clermont-Ferrand, France  \n3 Plateforme d’Investigation Clinique/Centre d’Investigation Clinique Inserm 1405, Bâtiment 3C, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France  \ncategorized into primary and secondary types. Primary chronic pain is not attributable to another underlying condition, whereas secondary forms include neuropathic, musculoskeletal, cancer-related, postsurgical, posttraumatic and visceral pain [4] . Despite the high prevalence of chronic pain, its treatment remains a significant challenge, with many patients experiencing inadequate relief from current, on-label and recommended therapies. Outcomes for patients experiencing chronic pain frequently remain suboptimal, with many treatments offering limited effectiveness and notable side effects [5] . Traditional pharmaceutical options, including opioids, antidepressants, and anticonvulsants, are commonly used but are often hindered by adverse effects that can restrict their therapeutic potential. In response, the search for alternative treatments has gained momentum, with ketamine, a N-methyl d aspartate (NMDA) receptor antagonist emerging as a promising option. The objectives of this narrative review of the literature are to synthesize and analyse current evidence on ketamine efficacy and safety in chroni","cbCaikKfse3Vw9fB","https://ap.wps.com/l/cbCaikKfse3Vw9fB","pdf",2776721,23,"English","# Abstract\n## 1 Introduction\n## 1.1 Chronic Pain\n## Key Points\n## 1.2 Ketamine\n### 1.2.1 History","[{\"question\":\"What is the main objective of the manuscript?\",\"answer\":\"To synthesize current evidence on ketamine’s efficacy and safety for chronic refractory pain, identify knowledge gaps, and propose a framework for rational and safe clinical use.\"},{\"question\":\"What does current evidence show about short-term ketamine effects?\",\"answer\":\"Ketamine can provide significant short-term analgesia, especially in neuropathic pain, and is fairly well tolerated in patients with severe refractory pain.\"},{\"question\":\"Why is ketamine not considered a first-line treatment for chronic pain?\",\"answer\":\"It is off-label, has psychomimetic side-effects and potential for addiction, and must be prescribed and supervised by trained specialists within a structured standard of care.\"}]","Managing Chronic Pain: The Ketamine Option | PDF",1790691537,58]