A Framework for Understanding the Relationship between Descending Pain Modulation, Motor Corticospinal, and Neuroplasticity Regulation Systems in Chronic Myofascial Pain.

Leonardo M Botelho,Joanna R Rozisky,Iraci L S Torres,Alicia Deitos,Aline P Brietzke,Felipe Fregni,Leon Morales-Quezada,Wolnei Caumo

doi:10.3389/fnhum.2016.00308

Abstract

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain. However, its neurobiological mechanisms are not entirely elucidated. Given the complex interaction between the networks involved in pain process, our approach, to providing insights into the neural mechanisms of pain, was to investigate the relationship between neurophysiological, neurochemical and clinical outcomes such as corticospinal excitability. Recent evidence has demonstrated that three neural systems are affected in chronic pain: (i) motor corticospinal system; (ii) internal descending pain modulation system; and (iii) the system regulating neuroplasticity. In this cross-sectional study, we aimed to examine the relationship between these three central systems in patients with chronic MPS of whom do/do not respond to the Conditioned Pain Modulation Task (CPM-task). The CPM-task was to immerse her non-dominant hand in cold water (0−1°C) to produce a heterotopic nociceptive stimulus. Corticospinal excitability was the primary outcome; specifically, the motor evoked potential (MEP) and intracortical facilitation (ICF) as assessed by transcranial magnetic stimulation (TMS). Secondary outcomes were the cortical excitability parameters [current silent period (CSP) and short intracortical inhibition (SICI)], serum brain-derived neurotrophic factor (BDNF), heat pain threshold (HPT), and the disability related to pain (DRP). We included 33 women, (18–65 years old). The MANCOVA model using Bonferroni's Multiple Comparison Test revealed that non-responders (n = 10) compared to responders (n = 23) presented increased intracortical facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater motor-evoked potential amplitude (μV) 1.93 (0.54) vs. 1.40 (0.27), as well a higher serum BDNF (pg/Ml) 32.56 (9.95) vs. 25.59 (10.24), (P < 0.05 for all). Also, non-responders presented a higher level of DRP and decreased HPT (P < 0.05 for all). These findings suggest that the loss of net descending pain inhibition was associated with an increase in ICF, serum BDNF levels, and DRP. We propose a framework to explain the relationship and potential directionality of these factors. In this framework we hypothesize that increased central sensitization leads to a loss of descending pain inhibition that triggers compensatory mechanisms as shown by increased motor cortical excitability.

Highlights

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain (Simons et al, 1999)
The reasons for exclusion were not fulfilling the diagnostic criteria for MPS, not present a neuropathic component according to the DN4 (Neuropathic Pain Diagnostic Questionnaire), lacking disability as defined in the protocol, and the presence of another diagnosis
This study confirmed our hypothesis that the descending pain modulation system as assessed according to a spectrum of responders and non-responders to Conditioned pain modulation (CPM)-task is simultaneously correlated with a disinhibition at the cortical level, as measured by intracortical facilitation (ICF) and with global neuroplasticity levels as determined by serum Brain-derived neurotrophic factor (BDNF)

Summary

Introduction

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain (Simons et al, 1999). The ascending portion of this circuit involves the spine reticular tract (Willer et al, 1999), which comprises modulatory systems such as the opioidergic (Le Bars et al, 1981; Willer et al, 1990), noradrenergic (Sanada et al, 2009; Makino et al, 2010), and serotonergic systems (Chitour et al, 1982) Given this complex interaction, our approach to provide insights into the neural mechanisms of pain was to investigate the relationship between neurophysiological, neurochemical, and clinical outcomes such as corticospinal excitability as indexed by transcranial magnetic stimulation (TMS) measurements, conditioned pain modulation (CPM) to measure the descendent endogenous inhibitory pain system and serum brain-derived neurotrophic factor (BDNF) as a critical marker of neuroplasticity. It has been shown that pain and disability are associated with an imbalance between excitatory and inhibitory systems as assessed by increased intracortical facilitation (ICF) and by a reduced current silent period (CSP; Vidor et al, 2014; a proxy of glutamatergic activity), a higher pain catastrophizing score (Volz et al, 2013a) and a higher trait anxiety score (Vidor et al, 2014)

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