Skin inflammatory reactions to capsaicin in rheumatoid arthritis patients compared to healthy controls

Document Type : Original Research Article


1 Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Traditional Persian Pharmacy, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: Previous studies have examined the role of sensory nerves and neural mediators in symmetrical joint inflammation and autoimmunity in rheumatoid arthritis (RA). In this study, we sought to examine the association between capsaicin skin test and disease activity in RA patients.
Materials and Methods: Eighty RA patients (case group) and 20 healthy volunteers were enrolled in this experiment. The subjects in case group were calcified to newly diagnosed patients and those previously diagnosed with RA. A topical solution of capsaicin (0.075%) was applied on the volar forearm during the skin test, and evaluations were done after 5, 10, and 20 min. The parameters recorded in capsaicin skin test were time to tingling, area of induration (cm2), and area of redness (cm2).
Results: A faster capsaicin skin reaction was observed in healthy controls compared to the case group (p=0.02). Newly diagnosed and previously diagnosed RA patients were not significantly different in terms of reaction latency (p=0.06). The redness area after 15 (p=0.04) and 20 (p=0.001) min was significantly larger in previously diagnosed RA patients than in newly diagnosed ones. The ​​area of redness and time to tingling did not show any difference between active and inactive RA patients, but after 15 and 20 min, the area of redness was significantly greater in inactive RA patients compared to active RA patients (p=0.01 and p=0.03, respectively).
Conclusion: This study suggested that capsaicin skin test is not an efficient tool for the examination of synovial inflammation and disease activity in RA.


Main Subjects

Arendt-Nielsen L, Skou ST, Nielsen TA, Petersen KK. 2015. Altered central sensitization and pain modulation in the CNS in chronic joint pain. Curr Osteoporos Rep, 13:225-234.
Borbély É, Sándor K, Markovics A, Kemény Á, Pintér E, Szolcsányi J, Quinn JP, McDougall JJ, Helyes Z. 2016. Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees. Inflammat Res, 65:725-736.
Casanueva B, Rodero B, Quintial C, Llorca J, González-Gay MA. 2013. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int, 33:2665-2670.
Caterina MJ, Leffler A, Malmberg A, Martin W, Trafton J, Petersen-Zeitz K, Koltzenburg M, Basbaum AI, Julius D. 2000. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 288:306-313.
Cervero F, Plenderleith M. 1987. Adjuvant arthritis in adult-rats treated at birth with capsaicin. Acta Physiol Hung, 69:497-500.
Cruwys S, Garrett N, Kidd B. 1995. Sensory denervation with capsaicin attenuates inflammation and nociception in arthritic rats. Neurosci Let, 193:205-207.
Engler A, Aeschlimann A, Simmen BR, Michel BA, Gay RE, Gay S, Sprott H. 2007. Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fibroblasts from patients with osteoarthritis and rheumatoid arthritis. Biochem Biophys Res Communicat, 359:884-888.
Hong S, Agresta L, Guo C, Wiley JW. 2008. The TRPV1 receptor is associated with preferential stress in large dorsal root ganglion neurons in early diabetic sensory neuropathy. J Neurochem, 105:1212-1222.
Horváth Á, Tékus V, Boros M, Pozsgai G, Botz B, Borbély É, Szolcsányi J, Pintér E, Helyes Z. 2016. Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: in vivo study using TRPA1-deficient mice. Arthrit Res Ther, 18:6.
Jolliffe V, Anand P, Kidd B. 1995. Assessment of cutaneous sensory and autonomic axon reflexes in rheumatoid arthritis. Ann Rheum Dis, 54:251.
Kelly S, Chapman R, Woodhams S, Sagar DR, Turner J, Burston J, Bullock C, Paton K, Huang J, Wong A, McWilliams DF. 2013. Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain. Ann Rheum Dis, 74:252-259.
Knotkova H, Pappagallo M, Szallasi A. 2008. Capsaicin (TRPV1 Agonist) therapy for pain relief: farewell or revival? Clin J Pain, 24:142-154.
Lin Q, Zou X, Ren Y, Wang J, Fang L, Willis W. 2004. Involvement of peripheral neuropeptide Y receptors in sympathetic modulation of acute cutaneous flare induced by intradermal capsaicin. Neuroscience, 123:337-347.
Markenson JA. 1996. Mechanisms of chronic pain. Am J Med, 101: S6-S18.
McInnes IB, Schett G. 2017. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet, 389:2328-2337.
Menkes C, Renoux M, Laoussadi S, Mauborgne A, Bruxelle J, Cesselin F. 1993. Substance P levels in the synovium and synovial fluid from patients with rheumatoid arthritis and osteoarthritis. J Rheumatol, 20:714-717.
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, 71:179-186.
O'Connor TM, O'Connell J, O'Brien DI, Goode T, Bredin CP, Shanahan F. 2004. The role of substance P in inflammatory disease. J Cell Physiol, 201:167-180.
Patowary P, Pathak MP, Zaman K, Raju P, Chattopadhyay P. 2017. Research progress of capsaicin responses to various pharmacological challenges. Biomed Pharmacother, 96:1501-1512.
Pigatto GR, Coelho IS, Aquino RS, Bauermann LF, Santos AR. 2017. Light-emitting diode phototherapy reduces nocifensive behavior induced by thermal and chemical noxious stimuli in mice: evidence for the involvement of capsaicin-sensitive central afferent fibers. Mol Neurobiol, 54:3205-3218.
Prescott ED, Julius D. 2003. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science, 300:1284-1288.
Romac JM, McCall SJ, Humphrey JE, Heo J, Liddle RA. 2008. Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis. Pancreas, 36:394-401.
Sacerdote P, Carrabba M, Galante A, Pisati R, Manfredi B, Panerai A. 1995. Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: effect of the nonsteroidal anti inflammatory drugs indomethacin, diclofenac and naproxen. Inflamm Res, 44:486-490.
Seki N, Shirasaki H, Kikuchi M, Himi T. 2007. Capsaicin induces the production of IL-6 in human upper respiratory epithelial cells. Life Sci, 80:1592-1597.
Simone DA, Sorkin LS, Oh U, Chung JM, Owens C, LaMotte RH, Willis WD. 1991. Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol, 66:228-246.
Walsh D, Mapp PI, Wharton J, Rutherford R, Kidd B, Revell P, Blake DR, Polak JM. 1992. Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis. Ann Rheum Dis, 51:313.
Wayne Marshall K, Chiu B, Inman RD. 1990. Substance P and arthritis: analysis of plasma and synovial fluid levels. Arthrit Rheumat J Am Coll Rheumatol, 33:87-90.