Sensory testing and topical capsaicin can characterize patients with rheumatoid arthritis.
CHEPs
Capsaicin
Rheumatoid arthritis
Journal
Clinical rheumatology
ISSN: 1434-9949
Titre abrégé: Clin Rheumatol
Pays: Germany
ID NLM: 8211469
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
08
10
2021
accepted:
19
04
2022
revised:
13
04
2022
pubmed:
3
5
2022
medline:
20
7
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS). We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)-based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]). The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = - 0.65; RA patients: g*max = 0.72). As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment. Key Points • The effect of topical capsaicin may represent the extent of TRPV1 sensitization in rheumatoid arthritis. • The effect of topical capsaicin on the amplitude level of CHEPs can unmask neuropathic symptoms. • The effect of topical capsaicin on CHEPs and HPTs can show the long-term consequences and the treatment success of RA patients in remission.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
METHODS
METHODS
We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)-based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
RESULTS
RESULTS
The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = - 0.65; RA patients: g*max = 0.72).
CONCLUSION
CONCLUSIONS
As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment. Key Points • The effect of topical capsaicin may represent the extent of TRPV1 sensitization in rheumatoid arthritis. • The effect of topical capsaicin on the amplitude level of CHEPs can unmask neuropathic symptoms. • The effect of topical capsaicin on CHEPs and HPTs can show the long-term consequences and the treatment success of RA patients in remission.
Identifiants
pubmed: 35499773
doi: 10.1007/s10067-022-06185-0
pii: 10.1007/s10067-022-06185-0
pmc: PMC9059678
doi:
Substances chimiques
Sensory System Agents
0
Capsaicin
S07O44R1ZM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2351-2360Informations de copyright
© 2022. The Author(s).
Références
Heiberg T, Kvien TK (2002) Preferences for improved health examined in 1,024 patients with rheumatoid arthritis: pain has highest priority. Arthritis Rheum 47(4):391–397. https://doi.org/10.1002/art.10515
doi: 10.1002/art.10515
pubmed: 12209485
Lee YC, Bingham CO 3rd, Edwards RR, Marder W, Phillips K, Bolster MB, Clauw DJ, Moreland LW, Lu B, Wohlfahrt A, Zhang Z, Neogi T (2018) Association between pain sensitization and disease activity in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Care Res 70(2):197–204. https://doi.org/10.1002/acr.23266
doi: 10.1002/acr.23266
Lee YC, Cui J, Lu B, Frits ML, Iannaccone CK, Shadick NA, Weinblatt ME, Solomon DH (2011) Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis Res Ther 13(3):R83. https://doi.org/10.1186/ar3353
doi: 10.1186/ar3353
pubmed: 21651807
pmcid: 3218896
Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA (2021) 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res 73(7):924–939. https://doi.org/10.1002/acr.24596
doi: 10.1002/acr.24596
Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, Mariette X, Müller-Ladner U, Mysler EF, da Silva JAP, Poór G, Pope JE, Rubbert-Roth A, Ruyssen-Witrand A, Saag KG, Strangfeld A, Takeuchi T, Voshaar M, Westhovens R, van der Heijde D (2020) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 79(6):685–699. https://doi.org/10.1136/annrheumdis-2019-216655
doi: 10.1136/annrheumdis-2019-216655
pubmed: 31969328
Sánchez-Flórez JC, Seija-Butnaru D, Valero EG, Acosta C, Amaya S (2021) Pain management strategies in rheumatoid arthritis: a narrative review. J Pain Palliat Care Pharmacother 35(4):291–299. https://doi.org/10.1080/15360288.2021.1973647
doi: 10.1080/15360288.2021.1973647
pubmed: 34623946
Ahmed S, Magan T, Vargas M, Harrison A, Sofat N (2014) Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensitization components in pain reporting. J Pain Res 7:579–588. https://doi.org/10.2147/jpr.s69011
doi: 10.2147/jpr.s69011
pubmed: 25378947
pmcid: 4207578
Mucke M, Cuhls H, Radbruch L, Baron R, Maier C, Tolle T, Treede RD, Rolke R (2014) Quantitative sensory testing. Schmerz (Berlin, Germany) 28 (6):635–646; quiz 647–638. https://doi.org/10.1007/s00482-014-1485-4
Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD (2006) Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain (London, England) 10(1):77–88. https://doi.org/10.1016/j.ejpain.2005.02.003
doi: 10.1016/j.ejpain.2005.02.003
Cruz-Almeida Y, Fillingim RB (2014) Can quantitative sensory testing move us closer to mechanism-based pain management? Pain Med (Malden, Mass) 15(1):61–72. https://doi.org/10.1111/pme.12230
doi: 10.1111/pme.12230
Heisler AC, Song J, Dunlop DD, Wohlfahrt A, Bingham CO 3rd, Bolster MB, Clauw DJ, Marder W, Phillips K, Neogi T, Lee YC (2019) Association of pain centralization and patient-reported pain in active rheumatoid arthritis. Arthritis Care Res. https://doi.org/10.1002/acr.23994
doi: 10.1002/acr.23994
Granovsky Y, Anand P, Nakae A, Nascimento O, Smith B, Sprecher E, Valls-Sole J (2016) Normative data for Adelta contact heat evoked potentials in adult population: a multicenter study. Pain 157(5):1156–1163. https://doi.org/10.1097/j.pain.0000000000000495
doi: 10.1097/j.pain.0000000000000495
pubmed: 26907092
Seifert CL, Nitzsche D, Valet M, Tolle TR, Sprenger T (2008) Contact heat evoked potentials for the evaluation of pain pathways. Der Nervenarzt 79 (8):899, 902–897. https://doi.org/10.1007/s00115-008-2465-7
Mouraux A, Iannetti GD (2018) The search for pain biomarkers in the human brain. Brain J Neurol 141(12):3290–3307. https://doi.org/10.1093/brain/awy281
doi: 10.1093/brain/awy281
Iannetti GD, Hughes NP, Lee MC, Mouraux A (2008) Determinants of laser-evoked EEG responses: pain perception or stimulus saliency? J Neurophysiol 100(2):815–828. https://doi.org/10.1152/jn.00097.2008
doi: 10.1152/jn.00097.2008
pubmed: 18525021
pmcid: 2525705
Malver LP, Brokjær A, Staahl C, Graversen C, Andresen T, Drewes AM (2014) Electroencephalography and analgesics. Br J Clin Pharmacol 77(1):72–95. https://doi.org/10.1111/bcp.12137
doi: 10.1111/bcp.12137
pubmed: 23593934
Rifbjerg-Madsen S, Christensen AW, Boesen M, Christensen R, Danneskiold-Samsoe B, Bliddal H, Bartels EM, Locht H, Amris K (2014) Can the painDETECT questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital’s Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study. BMJ Open 4(11):e006058. https://doi.org/10.1136/bmjopen-2014-006058
doi: 10.1136/bmjopen-2014-006058
pubmed: 25394817
pmcid: 4244416
Mucke M, Cuhls H, Radbruch L, Baron R, Maier C, Tolle T, Treede RD, Rolke R (2016) Quantitative sensory testing (QST). English version. Schmerz (Berlin, Germany). https://doi.org/10.1007/s00482-015-0093-2
Metting van Rijn AC, Peper A, Grimbergen CA (1990) High-quality recording of bioelectric events. Part 1 Interference reduction, theory and practice. Medical & biological engineering & computing 28(5):389–397 https://doi.org/10.1007/bf02441961
Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134(1):9–21. https://doi.org/10.1016/j.jneumeth.2003.10.009
doi: 10.1016/j.jneumeth.2003.10.009
pubmed: 15102499
M Anders B Anders M Kreuzer S Zinn C Walter 2020 Application of referencing techniques in EEG-based recordings of contact heat evoked potentials (CHEPS) Front Hum Neurosci 14 https://doi.org/10.3389/fnhum.2020.559969
Chang C-Y, Hsu S-H, Pion-Tonachini L, Jung T-P (2018) Evaluation of artifact subspace reconstruction for automatic EEG artifact removal, vol 2018. https://doi.org/10.1109/EMBC.2018.8512547
Blumenstiel K, Gerhardt A, Rolke R, Bieber C, Tesarz J, Friederich HC, Eich W, Treede RD (2011) Quantitative sensory testing profiles in chronic back pain are distinct from those in fibromyalgia. Clin J Pain 27(8):682–690. https://doi.org/10.1097/AJP.0b013e3182177654
doi: 10.1097/AJP.0b013e3182177654
pubmed: 21487289
Hoo ZH, Candlish J, Teare D (2017) What is an ROC curve? Emergency Med J EMJ 34(6):357–359. https://doi.org/10.1136/emermed-2017-206735
doi: 10.1136/emermed-2017-206735
Hentschke H, Stuttgen MC (2011) Computation of measures of effect size for neuroscience data sets. Eur J Neurosci 34(12):1887–1894. https://doi.org/10.1111/j.1460-9568.2011.07902.x
doi: 10.1111/j.1460-9568.2011.07902.x
pubmed: 22082031
Cohen J (1988) Statistical power analysis for the behavioral sciences. L. Erlbaum Associates, Hillsdale, N.J.
Joharatnam N, McWilliams DF, Wilson D, Wheeler M, Pande I, Walsh DA (2015) A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis. Arthritis Res Ther 17:11. https://doi.org/10.1186/s13075-015-0525-5
doi: 10.1186/s13075-015-0525-5
pubmed: 25600850
pmcid: 4363056
Edwards RR, Wasan AD, Bingham CO 3rd, Bathon J, Haythornthwaite JA, Smith MT, Page GG (2009) Enhanced reactivity to pain in patients with rheumatoid arthritis. Arthritis Res Ther 11(3):R61. https://doi.org/10.1186/ar2684
doi: 10.1186/ar2684
pubmed: 19413909
pmcid: 2714104
Terenzi R, Romano E, Manetti M, Peruzzi F, Nacci F, Matucci-Cerinic M, Guiducci S (2013) Neuropeptides activate TRPV1 in rheumatoid arthritis fibroblast-like synoviocytes and foster IL-6 and IL-8 production. Ann Rheum Dis 72(6):1107–1109. https://doi.org/10.1136/annrheumdis-2012-202846
doi: 10.1136/annrheumdis-2012-202846
pubmed: 23444195
Morris VH, Cruwys SC, Kidd BL (1997) Characterisation of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis. Pain 71(2):179–186
doi: 10.1016/S0304-3959(97)03361-7
Hsieh WS, Kung CC, Huang SL, Lin SC, Sun WH (2017) TDAG8, TRPV1, and ASIC3 involved in establishing hyperalgesic priming in experimental rheumatoid arthritis. Sci Rep 7(1):8870. https://doi.org/10.1038/s41598-017-09200-6
doi: 10.1038/s41598-017-09200-6
pubmed: 28827659
pmcid: 5566336
Carnevale V, Rohacs T (2016) TRPV1: a target for rational drug design. Pharmaceuticals (Basel, Switzerland) 9 (3). https://doi.org/10.3390/ph9030052
Koplas PA, Rosenberg RL, Oxford GS (1997) The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. J Neurosci Off J Soc Neurosci 17(10):3525–3537
doi: 10.1523/JNEUROSCI.17-10-03525.1997
Jensen TS, Finnerup NB (2014) Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 13(9):924–935. https://doi.org/10.1016/s1474-4422(14)70102-4
doi: 10.1016/s1474-4422(14)70102-4
pubmed: 25142459
Baron R, Maier C, Attal N, Binder A, Bouhassira D, Cruccu G, Finnerup NB, Haanpää M, Hansson P, Hüllemann P, Jensen TS, Freynhagen R, Kennedy JD, Magerl W, Mainka T, Reimer M, Rice AS, Segerdahl M, Serra J, Sindrup S, Sommer C, Tölle T, Vollert J, Treede RD (2017) Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain 158(2):261–272. https://doi.org/10.1097/j.pain.0000000000000753
doi: 10.1097/j.pain.0000000000000753
pubmed: 27893485
Jara LJ, López-Zamora B, Ordoñez-González I, Galaviz-Sánchez MF, Gutierrez-Melgarejo CI, Saavedra M, Vera-Lastra O, Cruz-Domínguez MP, Medina G (2021) The immune-neuroendocrine system in COVID-19, advanced age and rheumatic diseases. Autoimmun Rev 20(11):102946. https://doi.org/10.1016/j.autrev.2021.102946
doi: 10.1016/j.autrev.2021.102946
pubmed: 34509651
pmcid: 8428987
Madsen CS, Johnsen B, Fuglsang-Frederiksen A, Jensen TS, Finnerup NB (2012) Increased contact heat pain and shortened latencies of contact heat evoked potentials following capsaicin-induced heat hyperalgesia. Clin Neurophysiol Off J Int Federat Clin Neurophysiol 123(7):1429–1436. https://doi.org/10.1016/j.clinph.2011.11.032
doi: 10.1016/j.clinph.2011.11.032
Chao C-C, Hsieh S-C, Tseng M-T, Chang Y-C, Hsieh S-T (2008) Patterns of contact heat evoked potentials (CHEP) in neuropathy with skin denervation: correlation of CHEP amplitude with intraepidermal nerve fiber density. Clin Neurophysiol 119(3):653–661. https://doi.org/10.1016/j.clinph.2007.11.043
doi: 10.1016/j.clinph.2007.11.043
pubmed: 18164654
Atherton DD, Facer P, Roberts KM, Misra VP, Chizh BA, Bountra C, Anand P (2007) Use of the novel contact heat evoked potential stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fibre counts. BMC Neurol 7(1):21
doi: 10.1186/1471-2377-7-21
Wong MC, Chung JW (2011) Feasibility of contact heat evoked potentials for detection of diabetic neuropathy. Muscle Nerve 44(6):902–906. https://doi.org/10.1002/mus.22192
doi: 10.1002/mus.22192
pubmed: 22102460