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Neuropathic pain: an updated grading system for research and clinical practice
Open accessAbstract
The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.
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“To indicate probable neuropathic pain, pain must also be associated with sensory abnormalities (i.e., clinical signs such as allodynia and/or hyperalgesia) in the same neuroanatomical plausible distribution (Finnerup et al. 2016; Schmid et al. 2023).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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In the citing paper
“Lastly, to establish definite neuropathic pain, additional objective confirmation of a lesion or disease in the somatosensory nervous system that may explain the pain is required (Finnerup et al. 2016; Schmid et al. 2023).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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In the citing paper
“To indicate possible neuropathic pain, patients must meet two criteria. First, the medical history should prompt a possible explanation for neuropathic pain, and patients should present with clinical symptoms. Second, the experienced pain distribution must be neuroanatomically plausible (i.e., the experienced pain is likely to correspond to the patient's neurological damage) (Finnerup et al. 2016;”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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In the citing paper
“the Neuropathic Pain Special Interest Group (NeuPSIG) has developed a grading system for the identification of neuropathic pain (Finnerup et al. 2016; Schmid et al. 2023)”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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“Importantly, a possible diagnosis cannot replace the probable and definite certainty provided by NeuPSIG in clinical practice (Finnerup et al. 2016).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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In the citing paper
“Importantly, the algorithms used across diagnostic certainty levels do not yield a definitive diagnosis of neuropathic pain (i.e., not to be confused with definite neuropathic pain). Instead, the grading system evaluate the probability that the experienced pain is caused by neurological damage, with increasing certainty as more criteria are met (Finnerup et al. 2016).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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“Given these considerations and in line with existing guidelines, the establishment of a probable diagnosis of neuropathic pain may be adequate for prompting analgesic treatments in pwMS, provided that the patient has a valid diagnosis of MS (Finnerup et al. 2016; Treede et al. 2019).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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“Hence, achieving definite diagnostic certainty does not constitute absolute proof of central neuropathic pain but should rather be interpreted as a strong indication within the context of best clinical practice (Finnerup et al. 2016).”
From The Prevalence of Neuropathic Pain in Multiple Sclerosis—A Systematic Review and Meta‐Analysis Using the NeuPSIG Algorithm (2026) · cites this paper as Finnerup et al. 2016
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Citations
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“Sometimes, in addition to ongoing pain or alone, intermittent electric shock-like pain paroxysms dominate the spontaneous sorrow [11].”
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“…in which the patient fulfills McDonald criteria for MS (DIS = disseminated in space, DIT = disseminated in time, or PPMS = primary progressive MS) [12]; (2) continuous or recurrent pain after MS, with onset after established diagnosis of MS; (3) pain duration of at least three months; (4) pain is…”
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“Additionally, the medications prescribed according to current guidelines often lead to severe side effects [20].”
BackgroundNeuroanatomy of the nociceptive system: From nociceptors to brain networks
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“In those patients who were not graded as having “probable” neuropathic pain by this approach, the methodology adopted by Hasvik et al. [23] was used to classify patients with chronic low back pain according to the IASP neuropathic pain grading system [17].”
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“Gabapentinoids (gabapentin and pregabalin) are the first choice recommended drugs for the treatment of neuropathic pain in humans [1].”
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“Introduction Neuropathic pain is a common chronic pain condition encountered in clinical practice that is typically caused by a lesion or disease of the somatosensory nervous system.(1,2) Its main clinical manifestations in patients include spontaneous pain, allodynia, and hyperalgesia.”
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Chronic Pain in Parkinson’s Disease: Prevalence, Sex Differences, Regional Anatomy and Comorbidities
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“Therefore, chronic pain patients suffer drug tolerance, addiction and various side effects of taking overdoses of analgesics for long time (2).”
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Self-citationPain Science in Practice (Part 8): Nociceptive, Neuropathic, and Nociplastic Pain
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“The latest reports indicate that a considerable number of patients with chronic pain experience a combination of nociceptive and neuropathic pain features [6, 13, 14].”
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«Dolor mixto»: conceptualización actual y aproximación para Atención Primaria
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“Neuropathic pain, as defined by the International Association for the Study of Pain (IASP), is pain caused by lesions or diseases affecting the somatic sensory system, and it is a notable subtype of chronic pain [2].”
Atar, M. Ö., Kamacı, G. K., Özcan, F., Demir, Y., & Aydemir, K. (2022) · Journal of Trauma and Injury · doi:10.20408/jti.2022.0019 · Cited by 6
“NP is a direct result of a disease or lesion affecting the somatosensory system [9].”
BackgroundBelayneh, M., Fainsinger, R. L., Nekolaichuk, C., et al. (2022) · Journal of Palliative Medicine · doi:10.1089/jpm.2022.0187 · Cited by 6
“Moreover, relying on the classification of definite or probable Ne may provide a more conservative diagnosis of Ne.”
InfluentialYevgi, R., Laloğlu, E., & Bilge, N. (2023) · Revue Neurologique · doi:10.1016/j.neurol.2022.10.005 · Cited by 6
Sulistio, M., Ling, N., Finkelstein, T., et al. (2023) · Supportive Care in Cancer · doi:10.1007/s00520-023-07711-9 · Cited by 6
Pain and quality of life in athletes vs non-athletes with spinal cord injury: Observational study
Bella, G. P., Silveira‐Moriyama, L., & Cliquet, A. (2023) · Journal of Spinal Cord Medicine · doi:10.1080/10790268.2023.2253393 · Cited by 6
“Social participation may underlie the effect of sports, as it has been shown to have a protective effect on the impacts of chronic pain on mental health and quality of life (1, 4, 27).”
BackgroundGehr, N. L., Karlsson, P., Timm, S., Christensen, S., Hvid, C. A., Peric, J., Hansen, T. F., Lauritzen, L., Finnerup, N. B., & Ventzel, L. (2024) · BMC Cancer · doi:10.1186/s12885-024-11856-z · Cited by 6
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“Its main clinical manifestations include allodynia, spontaneous pain, and hyperalgesia (Finnerup et al., 2016; Xun et al., 2020).”
Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons
Subedi, A., Etemad, A., Tiwari, A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-74487-1 · Cited by 6
The Missing Link: Integrating Interventional Pain Management in the Era of Multimodal Oncology
Corriero, A., Giglio, M., Soloperto, R., Preziosa, A., Stefanelli, C., Castaldo, M., Gloria, F., Paladini, A., Guardamagna, V. A., & Puntillo, F. (2025) · Pain and Therapy · doi:10.1007/s40122-025-00755-1 · Cited by 9
Maiga, Y. M., Sangho, O., Konipo, F. D. N., Diallo, S. H., Coulibaly, S. D. P., Sangaré, M., Péréon, Y., Giumelli, B., Sanou, M., Coulibaly, A., et al. (2021) · eNeurologicalSci · doi:10.1016/j.ensci.2021.100312 · Cited by 5
“NeuP was presented as moderate to severe burning, paresthesias, tingling, searing pain, or numbness depending on the underlying causes, in keeping with the literature [12,30,31,36,37].”
ResultSelf-citationDevi, F. L. (2021) · Jurnal Penelitian Perawat Profesional · doi:10.37287/jppp.v3i1.370 · Cited by 6
Miclescu, A. A., Essemark, M., Astermark, M., Gkatziani, P., Straatmann, A., Butler, S. H., Karlsten, R., & Gordh, T. (2021) · PAIN Reports · doi:10.1097/pr9.0000000000000908 · Cited by 6
“The confirming sensory impairment on examination of the somatosensory system with pain in the innervation territory of a previous intraoperatively verified injured nerve and strongly indicated the diagnosis “definite neuropathic pain” for all the patients in group A.(10,37) The subjects with sensory impairment in the…”
BackgroundFiori, R., Forcina, M., Donna, C. D., et al. (2021) · The Neuroradiology Journal · doi:10.1177/19714009211000622 · Cited by 6
Increased Expression of Thymic Stromal Lymphopoietin in Chronic Constriction Injury of Rat Nerve
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Tampin, B., Lind, C. R. P., Jacques, A., & Slater, H. (2021) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2021-0058 · Cited by 6
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Internationale Klassifikation orofazialer Schmerzen (ICOP), 1. Auflage
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Persistent, neuropathic-like trigeminal pain after dental implant loading
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“-Clinical considerations According to the symptoms and clinical behavior, the patients were diagnosed as NP in line with IASP recommendations (19).”
Pain-motor integration in chronic pain: A neurophysiological study
Asci, F., Stefano, G. D., Santo, A. D., Bianchini, E., Leone, C. M., Cesa, S. L., Zampogna, A., Cruccu, G., & Suppa, A. (2023) · Clinical Neurophysiology · doi:10.1016/j.clinph.2023.07.010 · Cited by 6
Self-citationAn overview of diagnosis and assessment methods for neuropathic pain
Stefano, G. D., & Truini, A. (2024) · La Presse Médicale · doi:10.1016/j.lpm.2024.104234 · Cited by 6
Screening tools for neuropathic pain
Yang, C.-W., & Fuh, J. (2017) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2017.09.002 · Cited by 6
“Besides, certain pain descriptors are indicative, but not pathognomonic for NP, such as burning, electric shocks or shooting, pricking or pins and needles, pain evoked by light touch or cold, and associated sensations such as numbness and tingling.(4) Hence, screening questionnaires consist of several characteristic p…”
BackgroundDual role of D-amino acid oxidase in experimental pain models
Sharma, J., Kulshrestha, R., Singh, N., et al. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.05.001 · Cited by 6
Moriwaki, K., Shiroyama, K., Yasuda, M., & Uesugi, F. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000772 · Cited by 6
Patel, I. G., & Kamerman, P. R. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000778 · Cited by 6
Self-citationA randomized, controlled trial of a β2-agonist in painful polyneuropathy
Gillving, M., Demant, D. T., Holbech, J. V., Gylfadottir, S. S., Bach, F. W., Jensen, T. S., Finnerup, N. B., & Sindrup, S. H. (2020) · Pain · doi:10.1097/j.pain.0000000000002140 · Cited by 6
Self-citationKang, D.-H., & Kim, G.-W. (2020) · Brain Sciences · doi:10.3390/brainsci10120929 · Cited by 6
“According to the guidelines of the diagnosis and grading for neuropathic pain, all patients had neuropathic pain corresponding to a “probable grade” because the confirmatory test was not evaluated fully [16,24] (Figure 1).”
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An Advanced Practice Provider Guide to Peripheral Nerve Stimulation
Hoffmann, C. M., D'Souza, R. S., & Hagedorn, J. M. (2022) · Journal of Pain Research · doi:10.2147/jpr.s370037 · Cited by 6
“This begins with awareness of the neuropathic grading system (ie, possible, probable, or definite neuropathic pain), associated criteria and available screening instruments.(18) Screening instruments for the diagnosis of neuropathic pain include, but are not limited to, the Leeds assessment of Table 1 (Continued).”
BackgroundGarcía‐Martín, E., Tello, Á., Viladés, E., Pérez‐Velilla, J., Ciordía, B. C., Fernández‐Velasco, D., García‐Campayo, J., Puebla‐Guedea, M., & Satué, M. (2022) · Journal of Ophthalmology · doi:10.1155/2022/3946017 · Cited by 6
“Abnormalities in sensory signalling, including changes in key neurotransmitters and a reduction in descending control, have also been found to be associated with central sensitization in these patients [22].”
BackgroundBäckryd, E., Themistocleous, A. C., Larsson, A. O., Gordh, T., Rice, A. S. C., Tesfaye, S. H., Bennett, D., & Gerdle, B. U. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-66471-6 · Cited by 8
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“…on MRI in all participants, but either failed to assess bedside sensory examination [81] or failed to demonstrate sensory changes in more than 50% of the participants [59, 67, 81] and were therefore down-graded from definite to probable inclusion of participants with neuropathic pain [19, 31].”
InfluentialFarnes, N., Stubhaug, A., Hansson, P. T., & Vambheim, S. M. (2024) · Neuromodulation Technology at the Neural Interface · doi:10.1016/j.neurom.2024.09.002 · Cited by 7
Self-citationNeuroimage Signature in Post-Stroke Pain: A Systematic Review
Buzhanskyy, A., Duarte, I. C., Pato, M. V., Donato, H., Castelo-Branco, M. S., Abejas, A. G., & Lapa, T. A. S. C. (2025) · Current Pain and Headache Reports · doi:10.1007/s11916-024-01339-y · Cited by 7
“Neuropathic pain diagnosis should include the patient’s clinical history of neurological damage, with signs and symptoms corresponding with plausible damage in the CNS. Confirmatory tests are also needed to identify such dam - age in the somatosensory system [17, 43].”
Kapitza, C., Ballenberger, N., Luedtke, K., Schmid, A. B., & Tampin, B. (2025) · Pain · doi:10.1097/j.pain.0000000000003516 · Cited by 7
Cerebral Palsy Link to Sensorimotor System, Cognition, Emotion and Nociplastic Pain
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“…chronic relative ischaemia) [47]; - Neuropathic: Traumatic or metabolic peripheral and or central nerve damage (grading system according to IASP) [48]; - Nociplastic: Inflammatory maladaptation of the brain characterized by dysfunctional nociception and deficient pain inhibition (grading system…”
Understanding pain heterogeneity in osteoarthritis patients: a narrative review
Li, L., Fan, X., Crawford, R., Mao, X., Ong, L. J. Y., Gao, F., Sun, A. R., & Prasadam, I. (2025) · Frontiers of Medicine · doi:10.1007/s11684-025-1143-5 · Cited by 8
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“Neuropathic pain results from somatosensory system damage, while neuropathic-like pain mimics such features without confirmed injury [14].”
Ranathunga, N., Sterling, M. M., Sierra‐Silvestre, E., Chen, J., Schmid, A. B., Bisset, L., Coppieters, M. W., & Farrell, S. F. (2025) · Pain · doi:10.1097/j.pain.0000000000003826 · Cited by 8
The Implementation of Persistent Spinal Pain Syndrome ( PSPS ): Mechanism‐Based Recommendations
Thomson, S., Simpson, B. A., Huygen, F. J. P. M., Stanton-Hicks, M. D., North, R. B., Barolat, G., Scott, H., & Duarte, R. V. (2025) · Pain Practice · doi:10.1111/papr.70104 · Cited by 5
Hong, S., Piao, L., Cho, E.-H., Seo, E., & Kim, S. (2024) · International Journal of Medical Sciences · doi:10.7150/ijms.96236 · Cited by 5
“The International Association for the Study of Pain (IASP) defines neuropathic pain (NP) as “pain caused by a lesion or disease of the somatosensory nervous system” [1].”
BackgroundMills, E. P., Bosma, R., Rogachov, A., Cheng, J. C., Osborne, N., Kim, J. A., Besik, A., El-Sayed, R., Bhatia, A., & Davis, K. D. (2025) · Human Brain Mapping · doi:10.1002/hbm.70135 · Cited by 5
“A diagnosis of NP was made by one of the study co-investigators (A. Bhatia), and was consistent with the IASP algorithm for diagnosing NP (Finnerup et al. 2016) and the IASP definition of NP (https:// www. iasp-pain. org/ resou rces/ termi nology/ ).”
Metadata
- Authors
- Finnerup, N. B., Haroutounian, S., Kamerman, P., Baron, R., Bennett, D. L. H., Bouhassira, D., Cruccu, G., Freeman, R., Hansson, P., Nurmikko, T., Raja, S. N., Rice, A. S. C., Serra, J., Smith, B. H., Treede, R.-D., & Jensen, T. S.
- Affiliations
- Aarhus University (DK)
- Washington University in St. Louis (US)
- University of the Witwatersrand (ZA)
- University Hospital Schleswig-Holstein (DE)
- University of Oxford (GB)
- Inserm (FR)
- Sapienza University of Rome (IT)
- Beth Israel Deaconess Medical Center (US)
- Oslo University Hospital (NO)
- Walton Centre (GB)
- Johns Hopkins University (US)
- Chelsea and Westminster Hospital NHS Foundation Trust (GB)
- Neuroscience Technologies, Ltd, Barcelona, Spain
- University of Dundee (GB)
- Heidelberg University (DE)
- Corresponding author
- Finnerup, Nanna B.
- ORCID
- Venue
- Pain
- Published
- 2016-01-13
- Volume
- 157
- Issue
- 8
- Pages
- 1599-1606
- ISSN
- 0304-3959 (ISSN-L)
- 1872-6623
- PMC
- PMC4949003
- OpenAlex
- W2316569153
- Semantic Scholar
- 4d1325782b7eb15e39a0a2fafbff56c6b01dbb4c
- Cited by
- 1,332
- References
- 34
- Citations by year
- 2026: 116 · 2025: 155 · 2024: 134 · 2023: 198 · 2022: 138 · 2021: 164 · 2020: 131 · 2019: 120 · 2018: 97 · 2017: 57 · 2016: 17
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Pain (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- International Association for the Study of Pain
- Teva Pharmaceutical Industries
- Glenmark Pharmaceuticals
- European Commission (633491, HORIZON2020)
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Eisai
- Novo Nordisk (NNF14SA0006)
- Astellas Pharma
- Novo Nordisk Fonden (NNF14SA000 6, NNF14OC0011633)
- Allergan
- Sanofi Pasteur
- National Institute of General Medical Sciences
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
- Keywords
- neuropathic pain, neuropathic pain diagnosis, pain distribution, sensory disturbances, confirmatory testing, screening tool
- MeSH terms
- Humans, Neuralgia, Pain Measurement, Surveys and Questionnaires, Research, Pain Management
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