The Endogenous Pain Modulatory System as a Healing Mechanism: A Proposal on How to Measure and Modulate It

Author:

de Melo Paulo S.1ORCID,Pacheco-Barrios Kevin12,Marduy Anna1,Vasquez-Avila Karen1,Simis Marcel3,Imamura Marta3,Cardenas-Rojas Alejandra1ORCID,Navarro-Flores Alba4,Batistella Linamara3,Fregni Felipe1ORCID

Affiliation:

1. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, 96 13th Street, Charlestown, Boston, MA 02141, USA

2. Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima 15024, Peru

3. Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-060, Brazil

4. Escuela de Medicina, Universidad Cesar Vallejo, Trujillo 13001, Peru

Abstract

Background: Chronic pain is highly burdening and multifactorial in etiology. The endogenous-pain-healing system restores body tissue to a non-painful state after an injury leading to pain, and its disruption could represent a relevant mechanism, especially for nursing interventions. Aim: To review the literature and summarize the results that support this hypothesis. Methods: We hypothesized that the mechanism behind this system mainly depends on the endogenous pain modulatory system (EPMS), which is responsible for inhibiting pain after tissue healing is complete and facilitating it when tissue damage is still present. Different biomarkers can quantify EPMS functioning. We reviewed the literature and included relevant information regarding this hypothesis. Results: First, conditioned pain modulation (CPM) measures pain inhibition and is a possible predictor for pain chronification. Second, motor cortex excitability measures the cortical control of the EPMS, which can be assessed through transcranial magnetic stimulation (using intracortical inhibition) or electroencephalography. Modifiable factors disrupt its functioning, such as sleep deprivation, medication overuse, and mental health status, but could be protective, such as exercise, certain medications, mind–body techniques, and non-invasive neuromodulation therapies. The acquisition of neurophysiological knowledge of how the chronicity of pain occurs and the EPMS involvement in this process may allow for better management of these patients. Conclusions: We raised the hypothesis that the impairment of the EPMS (altered cortical excitability and descendent pain modulation pathways) seems to be related to the disruption of the pain healing process and its chronicity. Further longitudinal studies evaluating the relationship between these biomarkers and chronic pain development are necessary.

Funder

National Institutes of Health

Publisher

MDPI AG

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