Understanding How Opioids Contribute to Reward and Analgesia

Abstract

Opioids acting at the mu opioid (MOP) receptor produce powerful analgesia. They also produce an intensely rewarding effect that can lead to addiction. The analgesic effect of MOP receptor agonists derives from a direct inhibitory effect on pain transmission at the spinal-cord level and through activation of a descending pain-modulatory pathway. The rewarding effect of MOP agonists is the result of their actions in the mesostriatal dopamine pathway classically associated with both natural and drug rewards. Both the analgesic and rewarding effect of MOP agonists are best understood in the context of decision making under conditions of conflict. Pain is one of many competing motivational states, and endogenous opioids suppress responses to noxious stimuli in the presence of conflicting motivations, such as hunger or a threatening predator. When a food reward is available, MOP agonists microinjected into the mesostriatal circuit promote its consumption, while concomitantly suppressing responses to noxious stimulation. The mesostriatal "reward" circuit, thus, appears to perform a function critical to decision making and can either amplify or suppress responses to noxious stimuli.

Music and social bonding: “self-other” merging and neurohormonal mechanisms

“…The EOS consists of opioid receptors and associated ligands distributed throughout the central nervous system and peripheral tissues, such as the nucleus accumbens (Fields, 2007; Trigo et al, 2010). The EOS is central in opioid-mediated reward (Koob, 1992; Olmstead and Franklin, 1997; Comings et al, 1999), social motivation (Chelnokova et al, 2014), and pleasure and pain perception (Janal et al, 1984; Leknes and Tracey, 2008).…”

“…Positron emission tomography (PET) scans have confirmed the euphoric state that follows exercise (termed “runner’s high”) is due to endogenous opioids (Boecker et al, 2008). Further to the effect on mood, opioids have an analgesic effect (Van Ree et al, 2000), and much evidence suggests that endorphins are central in the pain management system (D’Amato and Pavone, 1993; Benedetti, 1996; Zubieta et al, 2001; Fields, 2007; Bodnar, 2008; Dishman and O’Connor, 2009; Mueller et al, 2010). Given that direct measures of endogenous opioids are costly and invasive (Dearman and Francis, 1983), pain threshold is a commonly used proxy measure of endorphin release, and this has been operationalised using the length of time holding a hand in ice water (Dunbar et al, 2012a,b), a ski exercise (maintaining a squat position with legs at right angles: Dunbar et al, 2012a), an electrocutaneous simulator (Jamner and Leigh, 1999), pressure produced using a blood pressure cuff (Cogan et al, 1987; Cohen et al, 2010; Dunbar et al, 2012a,b), and the amount of pain medication requested by patients (Zillmann et al, 1993).…”

‘Naltrexone Blocks Endorphins Released when Dancing in Synchrony’

“…The Endogenous Opioid System (EOS) -consisting of opioid receptors and associated peptides distributed throughout the central nervous system and peripheral tissues (Fields 2007;Trigo et al 2010) -plays an important role in human pleasure-pain circuitry (Mueller et al 2010). This system is instrumental in modulating mood (Koepp et al 2009;Zubieta et al 2003), feelings of euphoria (Bodnar 2008), interpersonal warmth, well-being and bliss (Comings et al 1999;Depue and Morrone-Strupinsky 2005;Ferrante 1996;Koob 1992) and the post-exercise 'high' (Boecker et al 2008).…”

“…The specific role of beta-endorphins in analgesia was first established in mice Tseng et al 1976), and subsequently in humans (Janal et al 1984;Leknes and Tracey 2008). Exogenous opioid agonists (such as morphine or opium) act similarly to endogenous opioids, such as endorphins (Belluzzi and Stein 1977;D'Amato and Pavone, 1993;Nelson and Panksepp 1998;Stefano et al 2000), in that they act at the level of the spinal cord to inhibit pain transmission (Fields 2007).…”

A Novel Role for the Periaqueductal Gray in Consummatory Behavior

“…This essential process is mediated by a complex circuitry that engages multiple regions of the brain such as prefrontal cortex, hypothalamus, hippocampus, ventral tegmental area, basal ganglia structures and more (Kelley et al, 2005). Indeed, it has been documented that expectancy of a food reward can activate endogenous opioid-mediated analgesia which is thought to be mediated by the PAG (Dum and Herz, 1984; Fields, 2004) and it is hypothesized that reward expectation elicits an analgesic response to allow an animal to ignore noxious stimuli and attend to a rewarding stimulus (Fields, 2007; Leknes and Tracey, 2008). …”