Respiratory muscle acidosis stimulates endogenous opioids during inspiratory loading

Activation of endogenous opioid pathways during intense inspiratory flow- resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMG(eo)) relative to the diaphragm (EMG(di)). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H₂O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMG(di) and EMG(eo), and respective muscle interstitial pH (pH(di), pH(eo)) using flexible pH probes. After 120 min IRL with saline, pH(di), and pH(eo) declined by -0.12 ± 0.03 (mean ± SEM) and -0.20 ± 0.04 units, respectively (p < 0.05, pH(di) versus pH(eo)). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMG(di) by 26.5 ± 6.1%, but EMG(eo) by 81.9 ± 13.3% (p < 0.05, EMG(di) versus EMG(eo)). DCA blunted both the change in pH(di) and pH(eo) during IRL (to -0.01 ± 0.01 and -0.08 ± 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMG(di) and EMG(eo) with NLX (to -1.0 ± 2.6% and 5.7 ± 5.8%, respectively) (p < 0.05, DCA versus saline). We conclude that: (1) respiratory muscle acidosis is the primary stimulus for activation of inhibitory opioid pathways during IRL; (2) opioid-mediated inhibition of the individual respiratory muscles during IRL varies directly with their degree of acidosis; (3) lactic acid is a major component of this acidosis.