Overall, these observations, and previous estimations of 41.1% for the prevalence of neuropathic pain in soft tissue syndromes,11 confirm that painDETECT scores can be high in all musculoskeletal conditions.
The second explanation could be that low-grade inflammation following lesions in musculoskeletal tissues can drive the granulation of tissues in some patients only. This could lead to the sprouting of tiny vessels and nerves in the scar area (as observed in chronic tendinitis33 and back pain21) following distal release of various chemokines or growth factors, such as nerve growth factor.22 However, this hypothesis is somewhat at odds with another unexpected finding of our cohort because the mean and median values of painDETECT appeared to be nearly identical in patients whose current pain episode began 1 week, 1 month, several months, 1 year, or several years before, based on their retrospective judgment (Fig. 3). Indeed, functional and very early changes in peripheral nerves or the central nervous system (ie, more neuroplastic than neuropathic, such as epigenetic changes in neurons and/or glial cells) could account more for the painDETECT scores than the sprouting of new nerves or anatomical lesions (such as those induced in entrapment neuropathies by chronic nerve compression or ischemia). For example, dysregulation of transcriptional repressors, such as neuron restrictive silencer factor, contributes to neuropathic pain through epigenetic mechanisms37 and repression (by neuron restrictive silencer factor) of Nav1.8, leading to hypoesthesia and the repression of mu-opioid receptor genes, resulting in the loss of endorphins and morphine analgesia.39
This study had several limitations: (1) this population may not be representative of patients seen in private practice; (2) patients with the most severe and active forms of inflammatory rheumatism or osteoarthritis were probably overrepresented; (3) physicians were asked to select the main condition leading to the outpatients visits, whereas some patients may have had several disorders, and comorbidities, such as diabetes, were not sought out as other possible sources of high painDETECT scores; (4) patient estimations of their daily pain and the time elapsed since the onset of their current pain were both subjective and retrospective; and (5) only 98 of 529 patients declared that their current episode of pain lasted for 1 year or less.
The authors have no conflict of interest to declare.
The authors thank Peggy Ageneau, Karine Fajolles, and Karen Batard for delivering the questionnaires to patients and verifying their completeness before the physician visits.
. Askin A, Özkan A, Tosun A, Demirdal ÜS, Isnac F. Quality of life and functional capacity are adversely affected in osteoarthritis
patients with neuropathic
pain. Kaohsiung J Med Sci 2017;33:152–8.
. Attal N, Perrot S, Fermanian J, Boussahira D. The neuropathic
components of chronic low back
pain: a prospective multicenter study using the DN4 Questionnaire. J Pain 2011;12:1080–7.
. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 2002;52:69–77.
. Blikman T, Rienstra W, van Raay JJAM, Dijkstra B, Bulstra SK, Stevens M, van den Akker-Scheek I. Neuropathic
-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis
. PLoS One 2018;13:e0199165.
. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lantéri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic
pain diagnostic questionnaire (DN4). PAIN 2005;114:29–36.
. Cappalleri JC, Koduru V, Bienen EJ, Sadosky A. Characterizing neuropathic
pain profiles: enriching interpretation of painDETECT
. Patient Relat Outcome Meas 2016;7:93–9.
. Cappelleri JC, Koduru V, Bienen EJ, Sadosky A. A cross-sectional study examining the psychometric properties of the painDETECT
measure in neuropathic
pain. J Pain Res 2015;8:159–67.
. Choi JH, Lee SH, Kim HR, Lee KA. Association of neuropathic
-like pain characteristics with clinical and radiographic features in patients with ankylosing spondylitis. Clin Rheumatol 2018;37:3077–86.
. Dougados M, Perrot S. Fibromyalgia and central sensitization in chronic inflammatory joint diseases. Joint Bone Spine 2017;84:511–13.
. Fernandes GS, Valdes AM, Walsh DA, Zhang W, Doherty M. Neuropathic
-like knee pain and associated risk factors: a cross-sectional study in a UK community sample. Arthritis
Res Ther 2018;27:215.
. Fishbain DA, Cole B, Lewis JE, Gao J. What is the evidence that neuropathic
pain is present in chronic low back
pain and soft tissue syndromes? An evidence-based structured review. Pain Med 2014;15:4–15.
. Freynhagen R, Baron R, Gockel U, Tölle TR. painDETECT
: a new screening questionnaire to identify neuropathic
components in patients with back
pain. Curr Med Res Opin 2006;22:1911–20.
. Fujimoto K, Inage K, Orita S, Yamashita M, Abe K, Yamagata M, Sainoh T, Akazawa T, Kinoshita T, Nemoto T, Hirayama J, Murata Y, Kotani T, Aoki Y, Eguchi Y, Sakuma T, Aihara T, Ishikawa T, Suseki K, Hanaoka E, Yamauchi K, Kubota G, Suzuki M, Sato J, Shiga Y, Kanamoto H, Inoue M, Kinoshita H, Koda M, Furuya T, Takahashi K, Ohtori S. The nature of osteoporotic low back
pain without acute vertebral fracture: a prospective multicenter study on the analgesic effect of monthly minodronic acid hydrate. J Orthop Sci 2017;22:613–17.
. Geler-Külcü D, Batibay S, Öztürk G, Mesci N. The association of neuropathic
pain and disease activity, functional level, and quality of life in patients with ankylosing spondylitis: a cross-sectional study. Turk J Med Sci 2018;48:257–65.
. Gok K, Cengiz G, Erol K, Ozgocmen S. Neuropathic
pain component in axial spondyloarthritis and the influence on disease burden. J Clin Rheumatol 2018;24:324–7.
. Gudala K, Ghai B, Bansal D. Usefulness of four commonly used neuropathic
pain screening questionnaires in patients with chronic low back
pain: a cross-sectional study. Korean J Pain 2017;30:51–8.
. Hasvik E, Haugen AJ, Gjerstad J, Grøvle L. Assessing neuropathic
pain in patients with low back
-related leg pain: comparing the painDETECT
Questionnaire with the 2016 NeuPSIG grading system. Eur J Pain 2018;22:1160–9.
. Ito S, Kobayashi D, Murasawa A, Narita I, Nakazono K. An analysis of the neuropathic
pain components in rheumatoid arthritis
patients. Intern Med 2018;57:479–85.
. Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? PAIN 2013;154:S10–28.
. Khangura RK, Sharma J, Bali A, Singh N, Jaggi AS. An integrated review on new targets in the treatment of neuropathic
pain. Korean J Physiol Pharmacol 2019;23:1–20.
. Krock E, Rosenzweig DH, Chabot-Doré AJ, Jarzem P, Weber MH, Ouellet JA, Stone LS, Haglund L. Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors. J Cell Mol Med 2014;18:1213–25.
. Krock E, Currie JB, Weber MH, Ouellet JA, Stone LS, Rosenzweig DH, Haglund L. Nerve growth factor is regulated by toll-like receptor 2 in human intervertebral discs. J Biol Chem 2016;291:3541–51.
. Lazaro RP. Neuropathic
symptoms and musculoskeletal
pain in carpal tunnel syndrome: prognostic and therapeutic implications. Surg Neurol 1997;47:115–7.
. Lecomte F, Gault N, Koné V, Lafoix C, Ginsburg C, Claessens YE, Pourriat JL, Vidal-Trecan G. Prevalence of neuropathic
pain in emergency patients: an observational study. Am J Emerg Med 2011;29:43–9.
. Martin ML, Blum SI, Liedgens H, Bushnell DM, McCarrier KP, Hatley NV, Ramasamy A, Freynhagen R, Wallace M, Argoff C, Eerdekens M, Kok M, Patrick DL. Mixed-methods development of a new patient-reported outcome instrument for chronic low back
pain: part 1-the patient assessment for low back
pain—symptoms (PAL-S). PAIN 2018;159:1045–55.
. Mathieson S, Maher CG, Terwee CB, Folly de Campos T, Lin CW. Neuropathic
pain screening questionnaires have limited measurement properties. A systematic review. J Clin Epidemiol 2015;68:957–66.
. Moltó A, Etcheto A, Gossec L, Boudersa N, Claudepierre P, Roux N, Lemeunier L, Martin A, Sparsa L, Coquerelle P, Soubrier M, Perrot S, Dougados M. Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers' effectiveness in axial spondyloarthritis: results of a prospective, multicentre study. Ann Rheum Dis 2018;77:533–40.
. Momi SK, Fabiane SM, Lachance G, Livshits G, Williams FM. Neuropathic
pain as part of chronic widespread pain: environmental and genetic influences. PAIN 2015;156:2100–6.
. Percie du Sert N, Rice AS. Improving the translation of analgesic drugs to the clinic: animal models of neuropathic
pain. Br J Pharmacol 2014;171:2951–63.
. Rifbjerg-Madsen S, Christensen AW, Christensen R, Hetland ML, Bliddal H, Kristensen LE, Danneskiold-Samsøe B, Amris K. Pain and pain mechanisms in patients with inflammatory arthritis
: a Danish nationwide cross-sectional DANBIO registry survey. PLoS One 2017;12:e0180014.
. Roberge P, Doré I, Menear M, Chartrand E, Ciampi A, Duhoux A, Fournier L. A psychometric evaluation of the French Canadian version of the Hospital Anxiety and Depression Scale in a large primary care population. J Affect Disord 2013;147:171–9.
. Salaffi F, Di Carlo M, Carotti M, Sarzi-Puttini P. The effect of neuropathic
pain symptoms on remission in patients with early rheumatoid arthritis
. Curr Rheumatol Rev 2018. doi: .
. Schubert TE, Weidler C, Lerch K, Hofstädter F, Straub RH. Achilles tendinosis is associated with sprouting of substance P positive nerve fibres. Ann Rheum Dis 2005;64:1083–6.
. Soni A, Wanigasekera V, Mezue M, Cooper C, Javaid MK, Price AJ, Tracey I. Central sensitisation in knee osteoarthritis
: relating pre-surgical brainstem neuroimaging and PainDETECT
based patient stratification to arthroplasty outcome. Arthritis
. Sonohata M, Tsuruta T, Mine H, Morimoto T, Mawatari M. The relationship between neuropathic
pain, and the function of the upper limbs based on clinical severity according to electrophysiological studies in patients with carpal tunnel syndrome. Open Orthop J 2013;7:99–102.
. Spahr N, Hodkinson D, Jolly K, Williams S, Howard M, Thacker M. Distinguishing between nociceptive and neuropathic
components in chronic low back
pain using behavioural evaluation and sensory examination. Musculoskelet Sci Pract 2017;27:40–8.
. Thompson R, Chan C. NRSF and its epigenetic effectors: new treatments for neurological disease. Brain Sci 2018;8:E226.
. Timmerman H, Wolff AP, Bronkhorst EM, Wilder-Smith OHG, Schenkels MJ, van Dasselaar NT, Huygen FJPM, Steegers MAH, Vissers KCP. Avoiding catch-22: validating the PainDETECT
in a in a population of patients with chronic pain. BMC Neurol 2018;18:91.
. Uchida H, Ma L, Ueda H. Epigenetic gene silencing underlies C-fiber dysfunctions in neuropathic
pain. J Neurosci 2010;30:4806–14.
. Ueda H, Uchida H. Epigenetic modification in neuropathic
pain. Curr Pharm Des 2015;21:849–67.
. Vaegter HB, Andersen PG, Madsen MF, Handberg G, Enggaard TP. Prevalence of neuropathic
pain according to the IASP grading system in patients with chronic non-malignant pain. Pain Med 2014;15:120–7.
. Wheeler PC. Neuropathic
pain may be common in chronic lower limb tendinopathy: a prospective cohort study. Br J Pain 2017;11:16–22.
. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70.