Endogenous opioids in the pre‐Bötzinger complex via action on mu opioid receptors are critical in maintaining normal breathing by preventing and/or depressing sighs (712.12)

Abstract

The PBC is pivotal in generating augmented breathings (sighs), but local endogenous neurotransmitters responsible for control of sigh are not fully understood. Owing to the abundant presence of MORs in the PBC and centrally inhibitory effect of opioids on VT, we hypothesized that endogenous PBC opioids, via action on local MORs, would play an important role in maintaining normal respiration by preventing and/or depressing sighs. In anesthetized and spontaneously breathing rats, we recorded the cardiorespiratory activities before and after microinjection of naloxone methiodide, a MOR antagonist (10 mM, ~15 nl), into the PBC (PBCNLX). PBCNLX triggered sighs or if present, enhanced the frequency of sighs (from 0.7 ± 0.3 to 13.6 ± 1.6 sighs/10 min, P < 0.001). We further defined the effect of intravenous (5 μg/kg) and intracisternal injection of fentanyl (1 μg/kg), a MOR agonist, on the PBCNLX‐induced sighs. The sighs were abolished by intravenous injection of fentanyl and largely suppressed by intracisternal injection. In conclusion, endogenous PBC opioids via action on MORs are essential in maintaining normal respiration by preventing and/or suppressing sighs, consistent with centrally inhibitory effect of exogenous MOR agent on sighs.Grant Funding Source: Supported by HL 107462 and ALA Grant RG‐191095‐N