Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients

ABSTRACT

Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache.

Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded.

Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain.

Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.

RESUMO

Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional.

Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados.

Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia.

Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.

migraine disorders - tension-type headache - adiponectin - chemokines - neurotrophic factors

transtornos de enxaqueca - cefaleia do tipo tensional - adiponectina - quimiocinas - fatores neurotróficos

• References

• 1 Silva Junior AA, Bigal M, Vasconcelos LP, Rodrigues J, Gomez RS, Krymchantowski AV et al. Prevalence and burden of headaches as assessed by the health family program. Headache. 2012;52(3):483-90. doi:10.1111/j.1526-4610.2012.02090.x
• 2 Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28(2):183-7. doi:10.1002/ana.410280213
• 3 Welch KM, Nagesh V, Aurora SK, Gelman N. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache. 2001;41(7):629-37. doi:10.1046/j.1526-4610.2001.041007629.x
• 4 Bendtsen L, Jensen R. Tension-type headache. Neurol Clin. 2009;27(2):525-35. doi:10.1016/j.ncl.2008.11.010
• 5 Fantuzzi G. Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol. 2008;121(2):326-30. doi:10.1016/j.jaci.2007.10.018
• 6 Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354(6):610-21. doi:10.1056/NEJMra052723
• 7 Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond). 2006;110(2):175-91. doi:10.1042/CS20050161
• 8 Peterlin BL, Bigal ME, Tepper SJ, Urakaze M, Sheftell FD, Rapoport AM. Migraine and adiponectin: is there a connection? Cephalalgia. 2007;27(5):435-46. doi:10.1111/j.1468-2982.2007.01306.x
• 9 Duarte H, Teixeira AL, Rocha NP, Domingues RB. Increased serum levels of adiponectin in migraine. J Neurol Sci. 2014;342(1-2):186-8. doi:10.1016/j.jns.2014.04.035
• 10 Duarte H, Teixeira AL, Rocha NP, Domingues RB. Increased interictal serum levels of CXCL8/IL-8 and CCL3/MIP-1α in migraine. Neurol Sci. 2014;36(2):203-8. doi:10.1007/s10072-014-1931-1
• 11 Koçer A, Koçer E, Memişoğullari R, Domaç FM, Yüksel H. Interleukin-6 levels in tension headache patients. Clin J Pain. 2010;26(8):690-3. doi:10.1097/AJP.0b013e3181e8d9b6
• 12 Domingues RB, Duarte H, Rocha NP, Teixeira AL. Reduced serum levels of adiponectin in tension-type headache. Clin Neurol Neurosurg. 2015;131:82-5. doi:10.1016/j.clineuro.2015.01.026
• 13 Domingues RB, Duarte H, Rocha NP, Teixeira AL. Increased serum levels of interleukin-8 in patients with tension-type headache. Cephalalgia. 2015;35(9):801-6. doi:10.1177/0333102414559734
• 14 Tanure MT, Gomez RS, Hurtado RC, Teixeira AL, Domingues RB. Increased serum levels of brain-derived neurotropic factor during migraine attacks: a pilot study. J Headache Pain. 2010;11(5):427-30. doi:10.1007/s10194-010-0233-0
• 15 Sarchielli P, Mancini ML, Floridi A, Coppola F, Rossi C, Nardi K et al. Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome. J Pain. 2007;8(9):737-45. doi:10.1016/j.jpain.2007.05.002
• 16 Martins LB, Duarte H, Ferreira AV, Rocha NP, Teixeira AL, Domingues RB. Migraine is associated with altered levels of neurotrophins. Neurosci Lett. 2015;587:6-10. doi:10.1016/j.neulet.2014.12.022
• 17 Fischer M, Wille G, Klien S, Shanib H, Holle D, Gaul C et al. Brain-derived neurotrophic factor in primary headaches. J Headache Pain. 2012;13(6):469-75. doi:10.1007/s10194-012-0454-5
• 18 Domingues RB, Duarte H, Rocha NP, Teixeira AL. Neurotrophic factors in tension-type headache. Arq Neuropsiquiatr. 2015;73(5):420-4. doi:10.1590/0004-282X20150000
• 19 The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24(1 Suppl):9-160.
• 20 Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber WH, Batenhorst A et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8):963-74. doi:10.1023/A:1026119331193
• 21 Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML et al. Cutaneous allodynia in the migraine population. Ann Neurol. 2008;63(2):148-58. 10.1002/ana.21211
• 22 Ochi-ishi R, Nagata K, Inoue T, Tozaki-Saitoh H, Tsuda M, Inoue K. Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia. Mol Pain. 2014;10(1):53. doi:10.1186/1744-8069-10-53
• 23 Freitag CM, Miller RJ. Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines? Front Cell Neurosci. 2014;8:238. doi:10.3389/fncel.2014.00238
• 24 Fidan I, Yüksel S, Ymir T, Irkeç C, Aksakal FN. The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine. J Neuroimmunol. 2006;171(1-2):184-8. doi:10.1016/j.jneuroim.2005.10.005
• 25 Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigemino vascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain. 2013;154 Suppl 1. doi:10.1016/j.pain.2013.07.021
• 26 Lippi G, Meschi T, Mattiuzzi C, Borghi L, Targher G. Adiponectin and migraine: systematic review of clinical evidence. Neurol Sci. 2014;35(8):1167-71. doi:10.1007/s10072-014-1719-3
• 27 Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache. 2006;46(Suppl s4):S182-91. doi:10.1111/j.1526-4610.2006.00602.x
• 28 Barbosa IG, Rocha NP, Bauer ME, Miranda AS, Huguet RB, Reis HJ. Chemokines in bipolar disorder: trait or state? Eur Arch Psychiatry Clin Neurosci. 2013;263(2):159-65. doi:10.1007/s00406-012-0327-6
• 29 Fontenelle LF, Barbosa IG, Luna JV, Sousa LP, Abreu MN, Teixeira AL. A cytokine study of adult patients with obsessive-compulsive disorder. Compr Psychiatry. 2012;53(6):797-804. doi:10.1016/j.comppsych.2011.12.00
• 30 Barbosa IG, Rocha NP, Miranda AS, Magalhães PV, Huguet RB, Souza LP et al. Increased levels of adipokines in bipolar disorder. J Psychiatr Res. 2012;46(3):389-93. doi:10.1016/j.jpsychires.2011.11.010