CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

Abstract

Opioid receptors and enkephalinergic nerve terminals are widely distributed throughout respiratory-related regions of the brainstem and in the phrenic motor nucleus of the spinal cord (Xia & Haddad, 1991; Laferriere et al. 1999; Wang et al. 2002; Haji et al. 2003a; Lonergan et al. 2003a,b; Strornetta et al. 2003). Since opiate drugs given systemically will act on opioid receptors with conjoint selectivity in all respiratory regions, respiratory depression is unlikely to be dependent on actions at a single site. Therapeutic doses of opioids given to most mammalian species depress respiratory rate, minute ventilation, alveolar–arterial gas exchange and respiratory responsiveness to hypoxia and hypercapnia (Jaffe & Martin, 1990). Opioid-mediated depression of respiration is due at least in part to direct effects on the brainstem respiratory network, which includes several sites of action in medullary and pontine regions (reviewed by Pattison, 2008; Lalley, 2008). The degree of opioid-mediated respiratory depression depends on agonist dose, opioid receptor density and the subtypes of opioid receptor in various respiratory regions. Species variability and stage of development are also factors (Santiago & Edelman, 1985). In the paragraphs to follow, we review results of studies that indicate that the pre-Botzinger complex (preBotC) is not essential for respiratory depression by systemically administered opioid analgesics.