Respondent learning in chronic pain: how precise is imprecision?

Letter To Editor:

We read the topical review by Moseley and Vlaeyen[11] with great interest. The authors propose “a new hypothesis of chronic pain,” termed the “imprecision hypothesis” that “explains the most common painful disorders.”

This hypothesis builds on classical conditioning and consists of 2 primary assumptions: (1) pain can be a conditioned response (CR) to initially neutral conditioned stimuli (CS) that are associated with initial painful events (unconditioned stimuli [US]); (2) the degree of generalization of such a CR to other stimuli depends on how precisely a “multisensory and meaningful event” during initial pain was encoded. In chronic pain, this encoding is assumed to be imprecise, leading to dysfunctional, exaggerated generalization.

Although we agree that both concepts contribute to chronic pain, we cannot concur with the authors that these are novel concepts. The role of classical conditioning in chronic pain is textbook knowledge. More than 35 years ago, Gentry and Bernal[4] proposed a stimulus–response model of the maintenance of chronic pain: acute pain leads to muscular tension, which in turn increases the pain experience. This sets a pain-tension cycle in motion that is complemented by avoidance, immobility, fatigue, and anxiety. Lethem et al.[8] specifically proposed that fear of pain may lead to avoidance and exaggerated pain perception.

Linton et al.[9] further elaborated the role of neutral stimuli in pain: a nociceptive stimulus (US) leads to pain that is accompanied by sympathetic activation, tension, and fear (unconditioned responses), which become associated with neutral stimuli present during the incident (CS). These CS then elicit arousal, muscular tension, and anxiety as CRs. The CRs facilitate the perception of a secondary pain, which may be of a different type than the original US.

Flor et al.[3] expanded this model to all levels of the pain response, including central processes.

Moseley and Vlaeyen write that their “idea is fundamentally different to the large body of work on aversive conditioning”. Indeed, there is a difference: while classical accounts assume that pain-related responses, not pain, are the CRs, they propose “to extend this associative learning framework of pain-related fear to an approach that has pain itself as the response”. However, all previous models considered pain as the end product of the conditioning process. That the pain itself is an immediate CR, however, is arguable. Linton et al.[9] concluded that “the conditioned response (CR) is not “pain,” but it can be pain provoking.” However, classical conditioning influences pain perception and can bring innocuous stimuli into a painful range (cf. Refs. 1,12).

Moseley and Vlaeyen hypothesize that more stimulus generalization occurs if the “encoding” of acute pain is “imprecise”. The authors assume that this is the case in chronic pain. However, they do not clarify the mechanisms of such “encoding” and the meaning of “imprecise”. The given examples for “imprecision” in chronic pain range from widespread pain to impaired tactile acuity and proprioception, cortical reorganization, and distorted mental body representations. Yet, these examples relate to very different levels of pain-related perception and it is likely that they stem from altered percepts due to learning-related modulatory processes that have been well described in perception and learning.

A relationship between perception and generalization has been shown in learning theory. For example, the “inverse hypothesis” by Guttmann and Kalish[6,7] states an inverse relationship between stimulus discrimination and generalization: the less an organism is able to discriminate stimuli, the stronger is the generalization. However, this hypothesis refers to the CS, not to the CR. At present, we do not know whether discrimination ability is reduced with respect to the CR and how this relates to generalization and chronic pain. Moreover, emotional, motivational, and cognitive processes likely also play a major role in generalization.[5]

In summary, the mechanisms of conditioning and generalization described in the “imprecision hypothesis” are important, but not novel, concepts in the understanding of chronic pain. That pain can result from conditioning has been discussed before. The term “imprecision” lacks precision. It might be more fruitful to investigate perceptual, emotional, cognitive, and motivational processes related to learning and pain within existing conceptual frameworks. Finally, it is unlikely that the primary disturbance is in the acquisition of pain-related responses, which is crucial for survival. Rather, extinction might be most important for chronicity processes.[2] We commend the authors for putting a new focus on respondent learning processes in pain, complementing operant learning accounts[10] and hope for a new focus of research on learning processes involved in chronic pain.

Conflict of interest statement

The authors have no conflicts of interest to declare.