Pain-relief learning in flies, rats, and man: basic research and applied perspectives

Abstract

Memories relating to a painful, negative event are adaptive and can be stored for a lifetime to support preemptive avoidance, escape, or attack behavior. However, under unfavorable circumstances such memories can become overwhelmingly powerful. They may trigger excessively negative psychological states and uncontrollable avoidance of locations, objects, or social interactions. It is therefore obvious that any process to counteract such effects will be of value. In this context, we stress from a basic-research perspective that painful, negative events are "Janus-faced" in the sense that there are actually two aspects about them that are worth remembering: What made them happen and what made them cease. We review published findings from fruit flies, rats, and man showing that both aspects, respectively related to the onset and the offset of the negative event, induce distinct and oppositely valenced memories: Stimuli experienced before an electric shock acquire negative valence as they signal upcoming punishment, whereas stimuli experienced after an electric shock acquire positive valence because of their association with the relieving cessation of pain. We discuss how memories for such punishment-and relief-learning are organized, how this organization fits into the threat-imminence model of defensive behavior, and what perspectives these considerations offer for applied psychology in the context of trauma, panic, and nonsuicidal self-injury.The acknowledged "negative" mnemonic effects of adverse experiences mostly relate to what happens before the onset of an aversive, painful event. However, there is a less widely acknowledged type of memory that relates to what happens after the offset of or after escape from such a painful event, at the moment of "relief" (Fig. 1) (we use "relief" to refer specifically to the acute effects of punishment offset; an equally legitimate yet broader use of the word in, e.g., "fear relief," encompasses any process that eases fear [Riebe et al. 2012]). Indeed, in experimental settings, it turns out that stimuli experienced before and during a punishing episode are later avoided as they signal upcoming punishment, whereas stimuli experienced after a painful episode can subsequently prompt approach behavior, arguably (Box 1) because of their association with the relieving cessation of pain (Konorski 1948;Smith and Buchanan 1954;Wolpe and Lazarus 1966;Zanna et al. 1970;Solomon and Corbit 1974;Schull 1979;Solomon 1980;Wagner 1981;Walasek et al. 1995;Tanimoto et al. 2004;Yarali et al. 2008Yarali et al. , 2009bAndreatta et al. 2010Andreatta et al. , 2012Yarali and Gerber 2010;Ilango et al. 2012;Navratilova et al. 2012;Diegelmann et al. 2013b); for a corresponding finding in the appetitive domain, see Hellstern et al. (1998) andFelsenberg et al. (2013). Such relief can both support the learning of the cues associated with the disappearance of the threat and reinforce those behaviors that helped to escape it. Obviously, the positive conditioned valence of and ensuing learned approach behavi...

Common microbehavioral “footprint” of two distinct classes of conditioned aversion

“…2). Also in adult flies, vertebrates and humans, conditioned aversion and conditioned approach can have different causes: a cue can be avoided because it predicts a punishment, or the end, or a lack of a reward (sometimes referred to as "frustration learning"), and it can be approached because it predicts a reward, or the end of a punishment (called "relief learning"), or the lack of a punishment (called "safety learning") (Rescorla and Wagner 1972;Dickinson and Dearing 1979;Gray 1987;Tanimoto et al 2004;Rogan et al 2005;Kim et al 2006;Andreatta et al 2010;Leknes et al 2011;Navratilova et al 2013;Marshall et al 2014;Mohammadi et al 2014; for review, see Seymour et al 2007;Gerber et al 2014;Kong et al 2014). Although these different types of memories can be discriminated conceptually, the question arises to which extent the lack of a reward can be seen as just another kind of punishment, and likewise the lack of punishment as just another kind of reward.…”

“…Animals can learn to avoid situations when these situations feature either something bad or the lack of something good, and to approach situations when they feature either something good or the lack of something bad (for review, see Seymour et al 2007;Gerber et al 2014;Kong et al 2014; see also Discussion). Understanding the processes that bring about conditioned approach or conditioned avoidance requires a model organism that on the one hand provides convenient experimental access for detailed analyses of sensory systems, brain networks, and specific motor actions, and on the other hand is capable of learning-modulated navigation.…”

Reward and motivation in pain and pain relief

“…Psychological investigations, however, suggest that satisfaction of an aversive state is rewarding and may be considered as one of the basic positive emotions 28 . Although the concept of pain relief as a reward has been observed in humans studies 29,30 , it has only recently been demonstrated in animals 31–33 . Analogous to observations in humans, relief of ongoing injury-induced pain produces a positive affective state (reward from pain relief) that can be reliably demonstrated by assessment of motivated behavior in rodents 34 .…”

Synapsin is required to “boost” memory strength for highly salient events

“…When the sequence of odor and shock is reversed such that the odor is presented only upon the pleasantly relieving cessation of shock (backward conditioning), flies subsequently approach that odor. Such "relief" memory typically is weaker than punishment memory, yielding scores of only PI ≈ 0.2, even at an optimal backward interval (Gerber et al 2014). Such relief memory is Synapsin-dependent.…”