Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

Abstract

This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient.

Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression

“…That morphine elicited an initial increase in fR is consistent with our previous evidence that this opioid initially enhances fR in conscious Sprague-Dawley rats by activation of peripheral μ-ORs (Henderson et al, 2013, 2014). Morphine lowered fR in the HX but not HC group.…”

“…As was expected (Henderson et al, 2013, 2014; May et al, 2013a), the increases in fR (and concomitant decreases in TI and Te) and Vt, Ve and Vt/Ti (respiratory drive) elicited by the HC and HX challenges were substantially smaller in morphine-treated SHAM rats than in their saline-treated counterparts. However, it was evident that the ventilatory depressant effects of morphine were substantially greater against HC than HX.…”

“…Ventilatory parameters were continuously recorded in unrestrained freely-moving rats via a whole-body 12-chamber plethysmography system (PLY 3223; BUXCO Inc., Wilmington, NC, USA), as detailed previously (Henderson et al, 2013, 2014; May et al, 2013a,b) and as diagrammed in Fig. 1.…”

“…Analgesic doses of morphine depress ventilation in humans by central and peripheral actions (Cepeda et al, 2003; Cashman and Dolin, 2004; Taylor et al, 2005) via activation of μ-ORs although co-activation of δ- or κ-ORs modulates μ-OR responses (Dahan et al, 2010; Trescott et al, 2008). In animals, opioids depress ventilation via central and peripheral mechanisms including (a) centrally-mediated depression of ventilatory drive, (b) chest-wall muscle rigidity, (c) increases in airways resistance, and (d) an increase pulmonary vascular resistance, which decreases gas-exchange (see Henderson et al, 2013, 2014; Shook et al, 1990). …”

Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial

“…Previously, the use of opioids was not allowed for analgesia during labor, but sufentanil is an exception with its positive effect on neonatal outcomes and parturients . However, some studies have found that sufentanil can result in respiratory inhibition to a certain degree, which is not conducive to awake intubation and difficult airways . Dexmedetomidine, a highly selective alpha‐2 adrenergic receptor agonist, is found to cause mild respiratory depression, maintain hemodynamic stability and allow awake intubation and parturients regaining awareness during sedation and analgesia, all of which make it a potential option for anesthesia in obstetrics .…”