Can addiction develop to the absence of a normally present negative stimulus?

Question

I am wondering, can someone become addicted to the absence or the removal of a negative stimulus? Normally, addiction is associated with pleasure-inducing drugs, like opiates and amphetamines as notorious examples. These compounds induce massive release of dopamine in the limbic system, ultimately leading to addiction. Addiction is a collection of behaviors:

Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission.

It is known that training can be assisted by positive reinforcement (well done! here's a candy), or by negative reinforcement (wrong! here's an electroshock). Can addiction be caused by either? In other words, suppose someone is constantly aware of something unpleasant (pain, itching, unwanted perceptions such as tinnitus (ringing in the ears), negative emotions or thoughts) can the removal/lessening of such a stimulus lead to an addiction of the means to remove it?

For the sake of the question I think it is sufficient to focus the question on one (e.g., craving), or several of the symptoms, as existing studies, if any, may have focused on only one or few of the symptoms of addiction.

In short: are there studies on the addiction to the absence / removal of a negative stimulus?

_{This question was fueled by the comments to an earlier question}

Answer 1

In short, the answer to your question

can someone become addicted to the absence or the removal of a negative stimulus?

is most definitely yes.

Whilst not intended to be used as “diagnostic criteria” for determining if addiction is present or not, the characteristics of addiction provided through the American Society of Addiction Medicine (ASAM) are widely present in most cases of addiction, and gives an outline of the mechanism required for what you could be talking about, and therefore your hypothesis definitely has legs. You only have to look at alcoholism as an example.

The mechanism works through positive reinforcement, which as you put it, "Well done! here's a candy" in which the "candy", as you will see below, can be pain relief.

The same ASAM link you gave also points out that

Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry.

Although experimental studies have produced mixed results, there has been a long-standing belief in the analgesic properties of alcohol and a meta-analysis of controlled experimental studies conducted by Thompson et al. (2016) found that alcohol has the ability to provide a sense of relief from pain.

• Alcohol resulted in a small increase in pain threshold.

• A moderate-large decrease in pain ratings was also observed.

• Higher blood alcohol content is associated with greater analgesia.

• Analgesic effects may contribute to alcohol dependence in those with persistent pain.

Alcohol is also a big problem amongst many seeking help from severe stress, depression and/or anxiety through negative urgency which is correlated with greater caudate nucleus activity to alcohol cues (Chester, et al. 2016).

This is because, as pointed out by Sharot (2012)

The caudate nucleus is one of the major targets for the brain’s dopaminergic system (Wise & Rompre, 1989). Dopamine is a principal neuromodulator for reward learning and reward-seeking behaviour (Bayer & Glimcher, 2005; Belin & Everitt, 2008; Schultz, 2001). In particular, dopamine is suggested to signal predictions of rewards, and errors in such prediction–providing a learning signal when predictions do not align with outcomes (Montague, Hymann & Cohen, 2004; Schultz, 2001, 2007).

Through the dependency on the false friend called Alcohol, there is the inability to consistently abstain from seeking relief from pain (emotional or physical) which is part of the impairment in behavioural control. The feelings of escape from physical pain or the emotional attachment to life's hardships, after a while, can lead to craving for the same feeling, either to remove the returning pain, or to prevent its return.

Diminished recognition of significant problems with their behaviours and interpersonal relationships forms another part of the impairment in behavioural control and can arise from this constant "need" for an alcoholic drink, and dysfunctional emotional responses develop.

References

Chester, D. S., Lynam, D. R., Milich, R., & DeWall, C. N. (2016). Craving versus control: Negative urgency and neural correlates of alcohol cue reactivity. Drug and alcohol dependence, 163, S25-S28. doi: 10.1016/j.drugalcdep.2015.10.036

Sharot, T. (2012). Chapter 3 - Predicting Emotional Reactions: Mechanisms, Bias and Choice. In R. Dolan & T. Sharot (Ed.), Neuroscience of Preference and Choice (pp. 53-72). Academic Press doi: 10.1016/B978-0-12-381431-9.00003-6

Thompson, T., Oram, C., Correll, C. U., Tsermentseli, S., & Stubbs, B. (2017). Analgesic effects of alcohol: a systematic review and meta-analysis of controlled experimental studies in healthy participants. The Journal of Pain, 18(5), 499-510. doi: 10.1016/j.jpain.2016.11.009

Answer 2

I think this involves more a discussion of what addiction is (or how it's conceptualized) rather than anything about the neuroscience of rewards and aversion.

I think it's uncontroversial that "typical" humans can experience both appetitive and aversive conditioning (Andreatta and Pauli, 2015). However, the issue is that addiction is not merely that, e.g. your definition mentions "diminished recognition of significant problems with one’s behaviors and interpersonal relationships".

A recent study (Myers et al., 2017) of addicts on methadone maintenance found that

On the initial training phase, both groups performed similarly on learning to obtain reward, but as memory load grew, the control group outperformed the addicted group on learning to avoid punishment.

This seems to suggest that people who are addicted don't just like some reward excessively, but perhaps (more interestingly) also fail to dislike enough the negative (aversive) effects of that stimulus. (This is not necessarily the most clear-cut study, because the addicts were not drug-free.) But if you want the dual of this notion inversing the roles of reward and aversion, it would have to be people who don't get enough reward from a positive stimulus, so the dual of addiction in this sense would be anhedonia. And not surprisingly anhedonia is a result of exposure to too much aversive stimuli, e.g. it's a feature of PTSD (Olson et al., 2017). But my take is also a bit simplistic, because anhedonia is also exhibited by drug addicts particularly in withdrawal (Hatzigiakoumis et al., 2011).

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Regarding the question update

In other words, suppose someone is constantly aware of something unpleasant (pain, itching, unwanted perceptions such as tinnitus (ringing in the ears), negative emotions or thoughts) can the removal/lessening of such a stimulus lead to an addiction of the means to remove it?

If we exclude the obvious physical-dependence drugs like opioids, we're still left with a notion of "medication overuse headache", which apparently can be caused by aspirin or acetaminophen:

In order to emphasise the regular intake of drugs as the basis of this form of headache, the new name “medication-overuse headache” (MOH) has now been introduced into the International Headache Society’s classification from 2004. [...]

There is now substantial evidence that all drugs used for the treatment of headache can cause MOH in patients with primary headache disorders. The use of drugs that lead to chronic MOH varies substantially from country to country and is influenced by cultural factors. In many patients it is difficult to identify a single causal substance, because 90% of patients take more than one compound at a time and each component of antimigraine drugs might induce headache. This has been shown even for substances such as aspirin and paracetamol.

(As you probably know, even aspirin or acetaminophen have potential negative effects, e.g. bleeding or kidney damage, respectively).

And while it may seem that MOH has nothing to do with addiction, some have suggested otherwise, e.g. a more recent (2017) review:

In line with the concept that patients with MOH share similar characteristics to persons with addiction [Cupini, 2010], some authors have suggested that mechanisms involved in dependence processes also apply to MOH [Fumal, 2006].

Obviously this is not quite a settled piece of science.

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Beyond medication for intrinsic pain, you'd have to consider torture and what people would do gain relief from that. Apparently almost anything:

Ali Soufan, a former FBI special agent with considerable experience interrogating al-Qaeda operatives, pointed out in Time that:

When they are in pain, people will say anything to get the pain to stop. Most of the time, they will lie, make up anything to make you stop hurting them. That means the information you're getting is useless.

He isn't alone in this assessment – a number of former intelligence people have expressed similar views, and his words are echoed by the US Army Training Manual's section on interrogation, which suggests that:

…the use of force is a poor technique, as it yields unreliable results, may damage subsequent collection efforts, and can induce the source to say whatever he thinks the interrogator wants to hear.

Surely saying anything is some kind of "impairment in behavioral control" (from the definition of addiction you gave), but it would be hard to find [published] scientific studies on torture nowadays (and I'm not talking about studies on after-effects).