Manual Therapy Reduces Pain Behavior and Oxidative Stress in a Murine Model of Complex Regional Pain Syndrome Type I.

Afonso S I Salgado,Daiana C Salm,Daniel F Martins,Leidiane Mazzardo-Martins,Fabricia Petronilho,Ana C C Kuci,William R Reed,Adair R S Santos,Lucineia G Danielski,Juliana Stramosk,Drielly Florentino,Luana R Souza,Daniela D Ludtke,Lisandro A Ceci,Gislaine T Rezin,Aline Gassenferth

doi:10.3390/brainsci9080197

Abstract

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to mimic CRPS-I. Animals received ankle joint mobilization 48h after the IR procedure, and response to mechanical stimuli was evaluated. For biochemical analyses, mitochondrial function as well as oxidative stress thiobarbituric acid reactive substances (TBARS), protein carbonyls, antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels were determined. IR induced mechanical hyperalgesia which was subsequently reduced by acute MT treatment. The concentrations of oxidative stress parameters were increased following IR with MT treatment preventing these increases in malondialdehyde (MDA) and carbonyls protein. IR diminished the levels of SOD and CAT activity and MT treatment prevented this decrease in CAT but not in SOD activity. IR also diminished mitochondrial complex activity, and MT treatment was ineffective in preventing this decrease. In conclusion, repeated sessions of MT resulted in antihyperalgesic effects mediated, at least partially, through the prevention of an increase of MDA and protein carbonyls levels and an improvement in the antioxidant defense system.

Highlights

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition that frequently develops after a deep tissue injury, such as a fracture or sprain, without nerve injury
We observed that the acute manual therapy (MT) treatment
The repeated daily MT treatments (2–7 or 7–11 days) decreased (p = 0.001) the mechanical hypersensitivity induced by IR when assessed 30 minutes after MT (Figure 2B,D)

Summary

Introduction

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition that frequently develops after a deep tissue injury, such as a fracture or sprain, without nerve injury. Symptoms typically begin in the distal part of the affected limb and spread to the unaffected or opposite limb [1,2,3,4,5,6,7] The pathophysiology of this syndrome remains unclear, inflammatory and neural mechanisms have been suggested as potential contributors. Individuals with CRPS-I suffer from alterations in central and peripheral nervous system processing leading to decreased pain pressure threshold and increased temporal summation of pain [8]. These physiological changes most likely involve OS changes, which are known to be an important mechanism following tissue injury and hypoxia [9,10]

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