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Updated: Jan 21, 2026

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Manual Therapy Reduces Pain Behavior and Oxidative Stress in a Murine Model of Complex Regional Pain Syndrome Type I
Afonso S I Salgado1,2, Juliana Stramosk2, Daniela D Ludtke2,3
1Coordinator of Integrative Physical Therapy Residency-Philadelphia University Center, Londrina 86020-000, Paraná, Brazil.
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.
Insights
Manual therapy (MT) effectively reduced pain and oxidative stress in a chronic post-ischemia pain model mimicking complex regional pain syndrome type I. MT improved antioxidant defenses and prevented key markers of cellular damage.
Area of Science:
- Biomedical Sciences
- Pain Research
- Neuroscience
Background:
- Complex regional pain syndrome type I (CRPS-I) is a debilitating chronic pain condition.
- The underlying mechanisms of CRPS-I involve oxidative stress and mitochondrial dysfunction.
- Current therapeutic options for CRPS-I have limitations.
Purpose of the Study:
- To investigate the efficacy of manual therapy (MT) in a rodent model of CRPS-I.
- To determine if MT can alleviate pain behavior and reduce oxidative stress.
- To explore the impact of MT on mitochondrial function and antioxidant enzyme activity.
Main Methods:
- A chronic post-ischemia pain (CPIP) model was established in male Swiss mice via ischemia-reperfusion (IR).
- Ankle joint mobilization (manual therapy) was administered 48 hours post-IR.
- Pain responses, mitochondrial complex activity, and oxidative stress markers (TBARS, protein carbonyls, SOD, CAT) were assessed.
Main Results:
- IR induced significant mechanical hyperalgesia, which was reduced by MT.
- MT prevented the IR-induced increase in malondialdehyde (MDA) and protein carbonyls.
- MT preserved catalase (CAT) activity but not superoxide dismutase (SOD) activity following IR.
- MT did not prevent the decrease in mitochondrial complex activity.
Conclusions:
- Manual therapy demonstrates antihyperalgesic effects in a preclinical model of CRPS-I.
- MT's benefits are partly mediated by reducing oxidative stress markers (MDA, protein carbonyls) and enhancing antioxidant defenses.
- Further research into MT for CRPS-I is warranted, considering its potential to modulate key pathological pathways.
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