title: Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology.
abstract: The central sensitization syndrome (CSS) encompasses disorders with overlapping symptoms in a structural pathology spectrum ranging from persistent nociception [e.g., osteoarthritis (OA)] to an absence of tissue injuries such as the one presented in fibromyalgia (FM) and myofascial pain syndrome (MPS). First, we hypothesized that these syndromes present differences in their cortical excitability parameters assessed by transcranial magnetic stimulation (TMS), namely motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and short intracortical facilitation (SICF). Second, considering that the presence of tissue injury could be detected by serum neurotrophins, we hypothesized that the spectrum of structural pathology (i.e., from persistent nociception like in OA, to the absence of tissue injury like in FM and MPS), could be detected by differential efficiency of their descending pain inhibitory system, as assessed by the conditioned pain modulation (CPM) paradigm. Third, we explored whether brain-derived neurotrophic factor (BDNF) had an influence on the relationship between motor cortex excitability and structural pathology. This cross-sectional study pooled baseline data from three randomized clinical trials. We included females (n = 114), aged 19-65 years old with disability by chronic pain syndromes (CPS): FM (n = 19), MPS (n = 54), OA (n = 27) and healthy subjects (n = 14). We assessed the serum BDNF, the motor cortex excitability by parameters the TMS measures and the change on numerical pain scale [NPS (0-10)] during CPM-task. The adjusted mean (SD) on the SICI observed in the absence of tissue injury was 56.36% lower than with persistent nociceptive input [0.31(0.18) vs. 0.55 (0.32)], respectively. The BDNF was inversely correlated with the SICI and with the change on NPS (0-10)during CPM-task. These findings suggest greater disinhibition in the motor cortex and the descending pain inhibitory system in FM and MPS than in OA and healthy subjects. Likewise, the inter-hemispheric disinhibition as well as the dysfunction in the descending pain modulatory system is higher in chronic pain without tissue injury compared to a structural lesion. In addition, they suggest that a greater level of serum BDNF may be involved in the processes that mediate the disinhibition of motor cortex excitability, as well as the function of descending inhibitory pain modulation system, independently of the physiopathology mechanism of musculoskeletal pain syndromes.
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation at UFRGSPorto Alegre, Brazil; Anesthesiologist, Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA)Porto Alegre, Brazil; Pain and Anesthesia in Surgery Department, School of Medicine, UFRGSPorto Alegre, Brazil.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation at UFRGSPorto Alegre, Brazil.
authors.forename: Alícia
authors.initials: A
authors.lastname: Deitos
authors.affiliation: Neuropsychophysiology Laboratory, CIPsi, School of Psychology (EPsi), University of Minho, Campus de Gualtar Braga, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Neuropsychophysiology Laboratory, CIPsi, School of Psychology (EPsi), University of Minho, Campus de Gualtar Braga, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Leite
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation at UFRGSPorto Alegre, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation at UFRGSPorto Alegre, Brazil.
authors.forename: Jairo Alberto
authors.initials: JA
authors.lastname: Dussán-Sarria
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation at UFRGSPorto Alegre, Brazil.
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Lopes Tarragó
authors.affiliation: Post-graduate Program in Health and Human Development, La Salle University Center Canoas, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Souza
authors.affiliation: Post-graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS)Porto Alegre, Brazil; Department of Pharmacology, Instituto de Ciências Básicas da Saúde, UFRGSPorto Alegre, Brazil.
authors.forename: Iraci Lucena da Silva
authors.initials: IL
authors.lastname: Torres
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
keywords: brain-derived neurotrophic factor; central sensitization; conditioned pain modulation; fibromyalgia; myofascial pain syndrome; osteoarthritis; short intracortical inhibition