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Published on: January 13, 2017
Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading
J J Petrozzino1, A T Scardella, T V Santiago
1Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|February 1, 1992
Summary
Lactic acid buildup in respiratory muscles during inspiratory flow-resistive loading (IRL) triggers the release of endogenous opioids. This finding identifies lactic acid as the key peripheral stimulus activating opioid pathways during breathing challenges.
Area of Science:
- Respiratory Physiology
- Neuroscience
- Biochemistry
Background:
- Inspiratory flow-resistive loading (IRL) in goats activates central opioid pathways, inhibiting respiratory muscles.
- The specific peripheral stimulus triggering this opioid release during IRL remains unidentified.
Purpose of the Study:
- To investigate the hypothesis that lactic acid mediates endogenous opioid release during IRL.
- To determine if blocking lactic acid formation prevents opioid-mediated respiratory muscle inhibition.
Main Methods:
- Unanesthetized goats underwent IRL with either saline or dichloroacetate (DCA), a lactic acid inhibitor.
- Electromyographic (EMG) activity of respiratory muscles (diaphragm, external oblique, external intercostal) was measured.
- Naloxone (NLX), an opioid antagonist, was administered to assess opioid pathway involvement.
Main Results:
- DCA significantly blocked the naloxone-induced augmentation of diaphragm, external oblique, and external intercostal EMG activity after IRL.
- EMGdi increased by 20.8% with saline vs. 1.2% with DCA.
- EMGeo increased by 116.6% with saline vs. 5.3% with DCA; EMGei increased by 43.8% with saline vs. -4.5% with DCA.
Conclusions:
- Lactic acid produced by contracting respiratory muscles is the peripheral stimulus for endogenous opioid pathway activation during IRL.
- This study elucidates a novel mechanism linking metabolic stress in respiratory muscles to central opioid modulation.
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