The Effect of Naloxone on Ketamine-induced Effects on Hyperalgesia and Ketamine-induced Side Effects in Humans

Abstract

In this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia.

Ketamine: 50 Years of Modulating the Mind

“…These channels may mediate the hypnotic effects of volatile anesthetics as well (Zhou et al, 2015). Although ketamine appears to play a role in opioid potentiation (Finck and Ngai, 1982; Smith et al, 1987; Pacheco et al, 2014), antinociceptive effects mediated by opioid receptors may vary based on receptor subtype (Mikkelsen et al, 1999; Pacheco et al, 2014). Inhibition of serotonin reuptake is another suggested as a mechanism by which ketamine may confer analgesic effects (Martin et al, 1982), and ketamine’s block of large-conductance K Ca channels (BK channels) preferentially suppresses spinal microglia hyperactivation after nerve injury and may explain its potent effects on neuropathic pain (Hayashi et al, 2011).…”

Nociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults

“…Finally, a few studies have suggested that, in some cases, opioid antagonists may actually inhibit pain (Volavka et al 1979;Tassorelli et al 1995;Janssen and Arntz 1997). More recent studies have also either failed to observe effects of opioid blockade on pain (McCubbin and Bruehl 1994;Mikkelsen et al 1999;Bruehl et al 2002;Edwards et al 2004), or have reported that the effects of opioid blockade varied as a function of subgroup membership (Schobel et al 1998;Bruehl and Chung 2006;McCubbin et al 2006). For example, Schoebel et al (1998) reported that naloxone increased mechanical pain responses in normotensives, but not borderline hypertensives.…”

The Responses to Pharmacological Challenges and Experimental Pain in Patients With Chronic Whiplash-Associated Pain

“…Ketamine is thought to act primarily at the NMDA receptor, but it may also have actions at sodium channels and at kappa and mu opioid receptors. 36 Widespread referred pain areas with proximal spread and/or pain on the posterior aspect of the lower limb after infusion of hypertonic saline into the right TA muscle were found in some of the patients that participated in the experimental pain tests, which also can be interpreted as an indication of central hyperexcitability. 18 Despite earlier reports of a relationship between temporal summation and NMDA receptor activation, we were unable to find any correlation between ketamine response and the variables indicating temporal summation.…”