Reward, motivation, and emotion of pain and its relief

Abstract

The experience of pain depends on interpretation of context and past experience that guide the choice of an immediate behavioral response and influence future decisions of actions to avoid harm. The aversive qualities of pain underlie its physiological role in learning and motivation. In this review, we highlight findings from human and animal investigations that suggest that both pain, and the relief of pain, are complex emotions that are comprised of feelings and their motivational consequences. Relief of aversive states, including pain, is rewarding. How relief of pain aversiveness occurs is not well understood. Termination of aversive states can directly provide relief as well as reinforce behaviors that result in avoidance of pain. Emerging preclinical data also suggests that relief may elicit a positive hedonic value that results from activation of neural cortical and mesolimbic brain circuits that may also motivate behavior. Brain circuits mediating the reward of pain relief, as well as relief-induced motivation are significantly impacted as pain becomes chronic. In chronic pain states, the negative motivational value of nociception may be increased while the value of the reward of pain relief may decrease. As a consequence, the impact of pain on these ancient, and conserved brain limbic circuits suggest a path forward for discovery of new pain therapies.

Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain

“…It contains an abundance of μ-opioid receptors (42), receives mesolimbic dopaminergic projections, and is thought to act as a limbic-motor interface (43) translating motivation into motor action. Midbrain dopaminergic projections to the NAc fire in response to both rewarding and aversive stimuli (44). Brain areas where hedonic and/or incentive value of stimuli are encoded such as orbitofrontal and ventromedial prefrontal cortex (45) and anterior insula (46) send projections to the NAc which in turn projects to the ventral pallidum (47) and lateral hypothalamus (48).…”

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…The role of specific musical structures (rhythm and pitch) in K.448 was studied in rodents and humans (85), whereas high periodicity was proposed to account for the antiseizure effects (73). Musical tempo modulate emotions (113) which can in turn affect pain processing (114,115). Exposure to K.448 was shown to activate the parasympathetic nervous system (33).…”

Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats

“…Activity avoidance is cognitive strategy where individuals will avoid engaging in activities for fear of experiencing pain, which can contribute to worsening health outcomes (Philips et al, 1987). Accordingly, chronic pain can engender a reorganization of cognitive strategies to avoid pain, while relief from pain can be rewarding (Becerra and Borsook, 2008; King et al, 2009; Navratilova et al, 2015; Porreca and Navratilova, 2017). These relationships between pain and negative affective states may drive the addictive potential of drugs of abuse.…”