Generic placeholder image

Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Central Sensitization and Pain: Pathophysiologic and Clinical Insights

Author(s): Michele Curatolo*

Volume 22, Issue 1, 2024

Published on: 06 September, 2023

Page: [15 - 22] Pages: 8

DOI: 10.2174/1570159X20666221012112725

Price: $65


Central sensitization is an increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input.

Aim: To explain how the notion of central sensitization has changed our understanding of pain conditions, discuss how this knowledge can be used to improve the management of pain, and highlight knowledge gaps that future research needs to address.

Methods: Overview of definitions, assessment methods, and clinical implications.

Results: Human pain models, and functional and molecular imaging have provided converging evidence that central sensitization occurs and is clinically relevant. Measures to assess central sensitization in patients are available; however, their ability to discriminate sensitization of central from peripheral neurons is unclear. Treatments that attenuate central sensitization are available, but the limited understanding of molecular and functional mechanisms hampers the development of target-specific treatments. The origin of central sensitization in human pain conditions that are not associated with tissue damage remains unclear.

Conclusion: The knowledge of central sensitization has revolutionized our neurobiological understanding of pain. Despite the limitations of clinical assessment in identifying central sensitization, it is appropriate to use the available tools to guide clinical decisions towards treatments that attenuate central sensitization. Future research that elucidates the causes, molecular and functional mechanisms of central sensitization would provide crucial progress towards the development of treatments that target specific mechanisms of central sensitization.

Keywords: Pain, central sensitization, pain mechanisms, pain therapy, diagnosis, translational research.

International Association for the Study of Pain (IASP). IASP Terminology. 2017. Available from:
Woolf, C.J. Evidence for a central component of post-injury pain hypersensitivity. Nature, 1983, 306(5944), 686-688.
[] [PMID: 6656869]
Woolf, C.J. Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 2011, 152(3)(Suppl.), S2-S15.
[] [PMID: 20961685]
Nijs, J.; George, S.Z.; Clauw, D.J.; Fernández-de-las-Peñas, C.; Kosek, E.; Ickmans, K.; Fernández-Carnero, J.; Polli, A.; Kapreli, E.; Huysmans, E.; Cuesta-Vargas, A.I.; Mani, R.; Lundberg, M.; Leysen, L.; Rice, D.; Sterling, M.; Curatolo, M. Central sensitisation in chronic pain conditions: Latest discoveries and their potential for precision medicine. Lancet Rheumatol., 2021, 3(5), e383-e392.
Gebhart, G.F. Descending modulation of pain. Neurosci. Biobehav. Rev., 2004, 27(8), 729-737.
[] [PMID: 15019423]
Grace, P.M.; Hutchinson, M.R.; Maier, S.F.; Watkins, L.R. Pathological pain and the neuroimmune interface. Nat. Rev. Immunol., 2014, 14(4), 217-231.
[] [PMID: 24577438]
Kuner, R. Central mechanisms of pathological pain. Nat. Med., 2010, 16(11), 1258-1266.
[] [PMID: 20948531]
Kuner, R. Spinal excitatory mechanisms of pathological pain. Pain, 2015, 156(Suppl. 1), S11-S17.
[] [PMID: 25789427]
Latremoliere, A.; Woolf, C.J. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J. Pain, 2009, 10(9), 895-926.
[] [PMID: 19712899]
Su, M.; Yu, S. Chronic migraine: A process of dysmodulation and sensitization. Mol. Pain, 2018, 1744806918767697.
[] [PMID: 29642749]
Quesada, C.; Kostenko, A.; Ho, I.; Leone, C.; Nochi, Z.; Stouffs, A.; Wittayer, M.; Caspani, O.; Brix Finnerup, N.; Mouraux, A.; Pickering, G.; Tracey, I.; Truini, A.; Treede, R.D.; Garcia-Larrea, L. Human surrogate models of central sensitization: A critical review and practical guide. Eur. J. Pain, 2021, 25(7), 1389-1428.
[] [PMID: 33759294]
Arendt-Nielsen, L.; Curatolo, M.; Drewes, A. Human experimental pain models in drug development: Translational pain research. Curr. Opin. Investig. Drugs, 2007, 8(1), 41-53.
[PMID: 17263184]
Arendt-Nielsen, L.; Curatolo, M. Mechanistic, translational, quantitative pain assessment tools in profiling of pain patients and for development of new analgesic compounds. Scand. J. Pain, 2013, 4(4), 226-230.
[] [PMID: 29913625]
Biurrun, M.J.A.; Schliessbach, J.; Vuilleumier, P.H.; Müller, M.; Musshoff, F.; Stamer, U.; Stüber, F.; Arendt-Nielsen, L.; Curatolo, M. Anti‐nociceptive effects of oxytocin receptor modulation in healthy volunteers a randomized, double‐blinded, placebo‐controlled study. Eur. J. Pain, 2021, 25(8), 1723-1738.
[] [PMID: 33884702]
Vuilleumier, P.H.; Besson, M.; Desmeules, J.; Arendt-Nielsen, L.; Curatolo, M. Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: A randomized placebo-controlled study. PLoS One, 2013, 8(3), e43896.
[] [PMID: 23554851]
O’Neill, S.; Manniche, C.; Graven-Nielsen, T.; Arendt-Nielsen, L. Generalized deep-tissue hyperalgesia in patients with chronic low-back pain. Eur. J. Pain, 2007, 11(4), 415-420.
[] [PMID: 16815054]
Arendt-Nielsen, L.; Nie, H.; Laursen, M.B.; Laursen, B.S.; Madeleine, P.; Simonsen, O.H.; Graven-Nielsen, T. Sensitization in patients with painful knee osteoarthritis. Pain, 2010, 149(3), 573-581.
[] [PMID: 20418016]
Gerber, R.K.H.; Nie, H.; Arendt-Nielsen, L.; Curatolo, M.; Graven-Nielsen, T. Local pain and spreading hyperalgesia induced by intramuscular injection of nerve growth factor are not reduced by local anesthesia of the muscle. Clin. J. Pain, 2011, 27(3), 240-247.
[] [PMID: 21178592]
Svensson, P.; Cairns, B.E.; Wang, K.; Arendt-Nielsen, L. Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain, 2003, 104(1), 241-247.
[] [PMID: 12855334]
Babenko, V.; Graven-Nielsen, T.; Svensson, P.; Drewes, A.M.; Jensen, T.S.; Arendt-Nielsen, L. Experimental human muscle pain and muscular hyperalgesia induced by combinations of serotonin and bradykinin. Pain, 1999, 82(1), 1-8.
[] [PMID: 10422653]
Curatolo, M.; Petersen-Felix, S.; Gerber, A.; Arendt-Nielsen, L. Remifentanil inhibits muscular more than cutaneous pain in humans. Br. J. Anaesth., 2000, 85(4), 529-532.
[] [PMID: 11064609]
Graven-Nielsen, T.; Arendt-Nielsen, L.; Svensson, P.; Jensen, T.S. Quantification of local and referred muscle pain in humans after sequential i.m. injections of hypertonic saline. Pain, 1997, 69(1), 111-117.
[] [PMID: 9060020]
Arendt-Nielsen, L.; Drewes, A.M.; Hansen, J.B.; Tage-Jensen, U. Gut pain reactions in man: An experimental investigation using short and long duration transmucosal electrical stimulation. Pain, 1997, 69(3), 255-262.
[] [PMID: 9085299]
Drewes, A.M.; Schipper, K.P.; Dimcevski, G.; Petersen, P.; Andersen, O.K.; Gregersen, H.; Arendt-Nielsen, L. Multi-modal induction and assessment of allodynia and hyperalgesia in the human oesophagus. Eur. J. Pain, 2003, 7(6), 539-549.
[] [PMID: 14575667]
Mohr Drewes, A.; Pedersen, J.; Reddy, H.; Rasmussen, K.; Funch-Jensen, P.; Arendt-Nielsen, L.; Gregersen, H. Central sensitization in patients with non-cardiac chest pain: A clinical experimental study. Scand. J. Gastroenterol., 2006, 41(6), 640-649.
[] [PMID: 16754535]
Dickenson, A.H.; Sullivan, A.F. Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following c fibre stimulation. Neuropharmacology, 1987, 26(8), 1235-1238.
[] [PMID: 2821443]
Neziri, A.Y.; Andersen, O.K.; Petersen-Felix, S.; Radanov, B.; Dickenson, A.H.; Scaramozzino, P.; Arendt-Nielsen, L.; Curatolo, M. The nociceptive withdrawal reflex: Normative values of thresholds and reflex receptive fields. Eur. J. Pain, 2010, 14(2), 134-141.
[] [PMID: 19505833]
Arendt-Nielsen, L.; Sonnenborg, F.A.; Andersen, O.K. Facilitation of the withdrawal reflex by repeated transcutaneous electrical stimulation: An experimental study on central integration in humans. Eur. J. Appl. Physiol., 2000, 81(3), 165-173.
[] [PMID: 10638373]
McPhee, M.E.; Vaegter, H.B.; Graven-Nielsen, T. Alterations in pronociceptive and antinociceptive mechanisms in patients with low back pain: A systematic review with meta-analysis. Pain, 2020, 161(3), 464-475.
[] [PMID: 32049888]
O’Brien, A.T.; Deitos, A.; Triñanes Pego, Y.; Fregni, F.; Carrillo-de-la-Peña, M.T. Defective endogenous pain modulation in fibromyalgia: A meta-analysis of temporal summation and conditioned pain modulation paradigms. J. Pain, 2018, 19(8), 819-836.
[] [PMID: 29454976]
Bannister, K.; Dickenson, A.H. What the brain tells the spinal cord. Pain, 2016, 157(10), 2148-2151.
[] [PMID: 27023423]
Price, T.J.; Prescott, S.A. Inhibitory regulation of the pain gate and how its failure causes pathological pain. Pain, 2015, 156(5), 789-792.
[] [PMID: 25719614]
Fernandes, C.; Pidal-Miranda, M.; Samartin-Veiga, N.; Carrillo-de-la-Peña, M.T. Conditioned pain modulation as a biomarker of chronic pain: A systematic review of its concurrent validity. Pain, 2019, 160(12), 2679-2690.
[] [PMID: 31365469]
Schliessbach, J.; Siegenthaler, A.; Streitberger, K.; Eichenberger, U.; Nüesch, E.; Jüni, P.; Arendt-Nielsen, L.; Curatolo, M. The prevalence of widespread central hypersensitivity in chronic pain patients. Eur. J. Pain, 2013, 17(10), 1-20.
[] [PMID: 23703952]
Andersen, O.K.; Gracely, R.H.; Arendt-Nielsen, L. Facilitation of the human nociceptive reflex by stimulation of Aβ-fibres in a secondary hyperalgesic area sustained by nociceptive input from the primary hyperalgesic area. Acta Physiol. Scand., 1995, 155(1), 87-97.
[] [PMID: 8553881]
Curatolo, M.; Müller, M.; Ashraf, A.; Neziri, A.Y.; Streitberger, K.; Andersen, O.K.; Arendt-Nielsen, L. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain. Pain, 2015, 156(11), 2373-2382.
[] [PMID: 26172555]
French, D.J.; France, C.R.; France, J.L.; Arnott, L.F. The influence of acute anxiety on assessment of nociceptive flexion reflex thresholds in healthy young adults. Pain, 2005, 114(3), 358-363.
[] [PMID: 15777861]
Rhudy, J.L.; Martin, S.L.; Terry, E.L.; France, C.R.; Bartley, E.J.; DelVentura, J.L.; Kerr, K.L. Pain catastrophizing is related to temporal summation of pain but not temporal summation of the nociceptive flexion reflex. Pain, 2011, 152(4), 794-801.
[] [PMID: 21316150]
Arendt-Nielsen, L.; Anker-Møller, E.; Bjerring, P.; Spangsberg, N. Onset phase of spinal bupivacaine analgesia assessed quantitatively by laser stimulation. Br. J. Anaesth., 1990, 65(5), 639-642.
[] [PMID: 2248841]
Granot, M.; Buskila, D.; Granovsky, Y.; Sprecher, E.; Neumann, L.; Yarnitsky, D. Simultaneous recording of late and ultra-late pain evoked potentials in fibromyalgia. Clin. Neurophysiol., 2001, 112(10), 1881-1887.
[] [PMID: 11595147]
Chen, A.C.N.; Herrmann, C.S. Perception of pain coincides with the spatial expansion of electroencephalographic dynamics in human subjects. Neurosci. Lett., 2001, 297(3), 183-186.
[] [PMID: 11137758]
Vuilleumier, P.H.; Arguissain, F.G.; Biurrun Manresa, J.A.; Neziri, A.Y.; Nirkko, A.C.; Andersen, O.K.; Arendt-Nielsen, L.; Curatolo, M. Psychophysical and electrophysiological evidence for enhanced pain facilitation and unaltered pain inhibition in acute low back pain patients. J. Pain, 2017, 18(11), 1313-1323.
[] [PMID: 28645867]
Napadow, V.; Sclocco, R.; Henderson, L.A. Brainstem neuroimaging of nociception and pain circuitries. Pain Rep., 2019, 4(4), e745-e745.
[] [PMID: 31579846]
Mouraux, A.; Iannetti, G.D. The search for pain biomarkers in the human brain. Brain, 2018, 141(12), 3290-3307.
[] [PMID: 30462175]
Moayedi, M.; Salomons, T.V.; Atlas, L.Y. Pain neuroimaging in humans: A primer for beginners and non-imagers. J. Pain, 2018, 19(9), 961.e1-961.e21.
[] [PMID: 29608974]
Younis, S.; Hougaard, A.; Vestergaard, M.B.; Larsson, H.B.W.; Ashina, M. Migraine and magnetic resonance spectroscopy: A systematic review. Curr. Opin. Neurol., 2017, 30(3), 246-262.
[] [PMID: 28240609]
Kumbhare, D.A.; Elzibak, A.H.; Noseworthy, M.D. Evaluation of chronic pain using Magnetic Resonance (MR) neuroimaging approaches. Clin. J. Pain, 2017, 33(4), 281-290.
[] [PMID: 27518493]
Coghill, R.C.; McHaffie, J.G.; Yen, Y.F. Neural correlates of interindividual differences in the subjective experience of pain. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8538-8542.
[] [PMID: 12824463]
Cook, D.B.; Lange, G.; Ciccone, D.S.; Liu, W.C.; Steffener, J.; Natelson, B.H. Functional imaging of pain in patients with primary fibromyalgia. J. Rheumatol., 2004, 31(2), 364-378.
[PMID: 14760810]
Giesecke, T.; Gracely, R.H.; Grant, M.A.B.; Nachemson, A.; Petzke, F.; Williams, D.A.; Clauw, D.J. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum., 2004, 50(2), 613-623.
[] [PMID: 14872506]
Gracely, R.H.; Petzke, F.; Wolf, J.M.; Clauw, D.J. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum., 2002, 46(5), 1333-1343.
[] [PMID: 12115241]
Archibald, J.; MacMillan, E.L.; Enzler, A.; Jutzeler, C.R.; Schweinhardt, P.; Kramer, J.L.K. Excitatory and inhibitory responses in the brain to experimental pain: A systematic review of MR spectroscopy studies. Neuroimage, 2020, 215, 116794.
[] [PMID: 32278899]
Thiaucourt, M.; Shabes, P.; Schloss, N.; Sack, M.; Baumgärtner, U.; Schmahl, C.; Ende, G. Posterior insular GABA levels inversely correlate with the intensity of experimental mechanical pain in healthy subjects. Neuroscience, 2018, 387, 116-122.
[] [PMID: 28978415]
Foerster, B.R.; Petrou, M.; Edden, R.A.E.; Sundgren, P.C.; Schmidt-Wilcke, T.; Lowe, S.E.; Harte, S.E.; Clauw, D.J.; Harris, R.E. Reduced insular γ-aminobutyric acid in fibromyalgia. Arthritis Rheum., 2012, 64(2), 579-583.
[] [PMID: 21913179]
Sommer, C.; Leinders, M.; Üçeyler, N. Inflammation in the pathophysiology of neuropathic pain. Pain, 2018, 159(3), 595-602.
[] [PMID: 29447138]
Salter, M.W.; Stevens, B. Microglia emerge as central players in brain disease. Nat. Med., 2017, 23(9), 1018-1027.
[] [PMID: 28886007]
Walker, A.K.; Kavelaars, A.; Heijnen, C.J.; Dantzer, R. Neuroinflammation and comorbidity of pain and depression. Pharmacol. Rev., 2014, 66(1), 80-101.
[] [PMID: 24335193]
Ren, K.; Dubner, R. Interactions between the immune and nervous systems in pain. Nat. Med., 2010, 16(11), 1267-1276.
[] [PMID: 20948535]
Albrecht, D.S.; Forsberg, A.; Sandström, A.; Bergan, C.; Kadetoff, D.; Protsenko, E.; Lampa, J.; Lee, Y.C.; Höglund, C.O.; Catana, C.; Cervenka, S.; Akeju, O.; Lekander, M.; Cohen, G.; Halldin, C.; Taylor, N.; Kim, M.; Hooker, J.M.; Edwards, R.R.; Napadow, V.; Kosek, E.; Loggia, M.L. Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation. Brain Behav. Immun., 2019, 75, 72-83.
[] [PMID: 30223011]
Loggia, M.L.; Chonde, D.B.; Akeju, O.; Arabasz, G.; Catana, C.; Edwards, R.R.; Hill, E.; Hsu, S.; Izquierdo-Garcia, D.; Ji, R.R.; Riley, M.; Wasan, A.D.; Zürcher, N.R.; Albrecht, D.S.; Vangel, M.G.; Rosen, B.R.; Napadow, V.; Hooker, J.M. Evidence for brain glial activation in chronic pain patients. Brain, 2015, 138(3), 604-615.
[] [PMID: 25582579]
Albrecht, D.S.; Ahmed, S.U.; Kettner, N.W.; Borra, R.J.H.; Cohen-Adad, J.; Deng, H.; Houle, T.T.; Opalacz, A.; Roth, S.A.; Melo, M.F.V.; Chen, L.; Mao, J.; Hooker, J.M.; Loggia, M.L.; Zhang, Y. Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients. Pain, 2018, 159(5), 968-977.
[] [PMID: 29419657]
Binshtok, A.M.; Wang, H.; Zimmermann, K.; Amaya, F.; Vardeh, D.; Shi, L.; Brenner, G.J.; Ji, R.R.; Bean, B.P.; Woolf, C.J.; Samad, T.A. Nociceptors are interleukin-1beta sensors. J. Neurosci., 2008, 28(52), 14062-14073.
[] [PMID: 19109489]
Mayer, S.; Izydorczyk, I.; Reeh, P.W.; Grubb, B.D. Bradykinin-induced nociceptor sensitisation to heat depends on cox-1 and cox-2 in isolated rat skin. Pain, 2007, 130(1), 14-24.
[] [PMID: 17196338]
Neumann, S.; Doubell, T.P.; Leslie, T.; Woolf, C.J. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature, 1996, 384(6607), 360-364.
[] [PMID: 8934522]
Curatolo, M. Diagnosis of altered central pain processing. Spine, 2011, 36(25)(Suppl.), S200-S204.
[] [PMID: 22020613]
Banic, B.; Petersen-Felix, S.; Andersen, O.K.; Radanov, B.P.; Villiger, M.P.; Arendt-Nielsen, L.; Curatolo, M. Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia. Pain, 2004, 107(1), 7-15.
[] [PMID: 14715383]
Johansen, M.K.; Graven-Nielsen, T.; Olesen, A.S.; Arendt-Nielsen, L. Generalised muscular hyperalgesia in chronic whiplash syndrome. Pain, 1999, 83(2), 229-234.
[] [PMID: 10534594]
Sterling, M.; Jull, G.; Vicenzino, B.; Kenardy, J. Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery. Pain, 2003, 104(3), 509-517.
[] [PMID: 12927623]
Farrell, S.F.; Zoete, R.M.J.; Cabot, P.J.; Sterling, M. Systemic inflammatory markers in neck pain: A systematic review with meta‐analysis. Eur. J. Pain, 2020, 24(9), 1666-1686.
[] [PMID: 32621397]
Farrell, S.F.; Sterling, M.; Irving-Rodgers, H.; Schmid, A.B. Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study. Eur. J. Pain, 2020, 24(6), 1045-1057.
[] [PMID: 32096260]
Kosek, E.; Clauw, D.; Nijs, J.; Baron, R.; Gilron, I.; Harris, R.E.; Mico, J.A.; Rice, A.S.C.; Sterling, M. Chronic nociplastic pain affecting the musculoskeletal system: Clinical criteria and grading system. Pain, 2021, 162(11), 2629-2634.
[] [PMID: 33974577]
Neziri, A.Y.; Curatolo, M.; Limacher, A.; Nüesch, E.; Radanov, B.; Andersen, O.K.; Arendt-Nielsen, L.; Jüni, P. Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain. Pain, 2012, 153(10), 2083-2091.
[] [PMID: 22846347]
Backonja, M.M.; Attal, N.; Baron, R.; Bouhassira, D.; Drangholt, M.; Dyck, P.J.; Edwards, R.R.; Freeman, R.; Gracely, R.; Haanpaa, M.H.; Hansson, P.; Hatem, S.M.; Krumova, E.K.; Jensen, T.S.; Maier, C.; Mick, G.; Rice, A.S.; Rolke, R.; Treede, R.D.; Serra, J.; Toelle, T.; Tugnoli, V.; Walk, D.; Walalce, M.S.; Ware, M.; Yarnitsky, D.; Ziegler, D. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain, 2013, 154(9), 1807-1819.
[] [PMID: 23742795]
Boudreau, S.A.; Badsberg, S.; Christensen, S.W.; Egsgaard, L.L. Digital pain drawings. Clin. J. Pain, 2016, 32(2), 139-145.
[] [PMID: 25756558]
Petrie, K.J.; Frampton, T.; Large, R.G.; Moss-Morris, R.; Johnson, M.; Meechan, G. What do patients expect from their first visit to a pain clinic? Clin. J. Pain, 2005, 21(4), 297-301.
[] [PMID: 15951646]
Chen, B.; Duan, J.; Wen, S.; Pang, J.; Zhang, M.; Zhan, H.; Zheng, Y. An updated systematic review and meta-analysis of duloxetine for knee osteoarthritis pain. Clin. J. Pain, 2021, 37(11), 852-862.
[] [PMID: 34483232]
Chou, R.; Deyo, R.; Friedly, J.; Skelly, A.; Weimer, M.; Fu, R.; Dana, T.; Kraegel, P.; Griffin, J.; Grusing, S. Systemic pharmacologic therapies for low back pain: A systematic review for an american college of physicians clinical practice guideline. Ann. Intern. Med., 2017, 166(7), 480-492.
[] [PMID: 28192790]
Ferreira, G.E.; McLachlan, A.J.; Lin, C.W.C.; Zadro, J.R.; Abdel-Shaheed, C.; O’Keeffe, M.; Maher, C.G. Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: Systematic review and meta-analysis. BMJ, 2021, 372, m4825.
[] [PMID: 33472813]
Humble, S.R.; Dalton, A.J.; Li, L. A systematic review of therapeutic interventions to reduce acute and chronic post-surgical pain after amputation, thoracotomy or mastectomy. Eur. J. Pain, 2014.
[PMID: 25088289]
Zorrilla-Vaca, A.; Stone, A.; Caballero-Lozada, A.F.; Paredes, S.; Grant, M.C. Perioperative duloxetine for acute postoperative analgesia: A meta-analysis of randomized trials. Reg. Anesth. Pain Med., 2019, 44(10), 959-965.
[] [PMID: 31375539]
Moore, A.; Derry, S.; Wiffen, P. Gabapentin for chronic neuropathic pain. JAMA, 2018, 319(8), 818-819.
[] [PMID: 29486015]
Enke, O.; New, H.A.; New, C.H.; Mathieson, S.; McLachlan, A.J.; Latimer, J.; Maher, C.G.; Lin, C.W.C. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: A systematic review and meta-analysis. CMAJ, 2018, 190(26), E786-E793.
[] [PMID: 29970367]
Cooper, T.E.; Derry, S.; Wiffen, P.J.; Moore, R.A. Gabapentin for fibromyalgia pain in adults. Cochrane Database Syst. Rev., 2017, 1, CD012188.
[PMID: 28045473]
Deyo, R.A.; Von Korff, M.; Duhrkoop, D. Opioids for low back pain. BMJ, 2015, 350(jan05 10), g6380.
[] [PMID: 25561513]
Tölle, T.; Fitzcharles, M.A.; Häuser, W. Is opioid therapy for chronic non-cancer pain associated with a greater risk of all-cause mortality compared to non-opioid analgesics? A systematic review of propensity score matched observational studies. Eur. J. Pain, 2021, 25(6), 1195-1208.
[] [PMID: 33533519]
Mao, J. Opioid-induced abnormal pain sensitivity: Implications in clinical opioid therapy. Pain, 2002, 100(3), 213-217.
[] [PMID: 12467992]
Angst, M.S.; Clark, J.D. Opioid-induced hyperalgesia. Anesthesiology, 2006, 104(3), 570-587.
[] [PMID: 16508405]
Arribas-Romano, A.; Fernández-Carnero, J.; Molina-Rueda, F.; Angulo-Diaz-Parreño, S.; Navarro-Santana, M.J. Efficacy of physical therapy on nociceptive pain processing alterations in patients with chronic musculoskeletal pain: A systematic review and meta-analysis. Pain Med., 2020, 21(10), 2502-2517.
[] [PMID: 32100027]
Rice, D.; Nijs, J.; Kosek, E.; Wideman, T.; Hasenbring, M.I.; Koltyn, K.; Graven-Nielsen, T.; Polli, A. Exercise-induced hypoalgesia in pain-free and chronic pain populations: State of the art and future directions. J. Pain, 2019, 20(11), 1249-1266.
[] [PMID: 30904519]
Årnes, A.P.; Nielsen, C.S.; Stubhaug, A.; Fjeld, M.K.; Hopstock, L.A.; Horsch, A.; Johansen, A.; Morseth, B.; Wilsgaard, T.; Steingrímsdóttir, Ó.A. Physical activity and cold pain tolerance in the general population. Eur. J. Pain, 2021, 25(3), 637-650.
[] [PMID: 33165994]
Jull, G.; Sterling, M.; Kenardy, J.; Beller, E. Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash? - A preliminary RCT. Pain, 2007, 129(1), 28-34.
[] [PMID: 17218057]
Niknejad, B.; Bolier, R.; Henderson, C.R., Jr; Delgado, D.; Kozlov, E.; Löckenhoff, C.E.; Reid, M.C. Association between psychological interventions and chronic pain outcomes in older adults. JAMA Intern. Med., 2018, 178(6), 830-839.
[] [PMID: 29801109]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy