Neural Habituation to Painful Stimuli Is Modulated by Dopamine: Evidence from a Pharmacological fMRI Study

Abstract

In constantly changing environments, it is crucial to adaptively respond to threatening events. In particular, painful stimuli are not only processed in terms of their absolute intensity, but also with respect to their context. While contextual pain processing can simply entail the repeated processing of information (i.e., habituation), it can, in a more complex form, be expressed through predictions of magnitude before the delivery of nociceptive information (i.e., adaptive coding). Here, we investigated the brain regions involved in the adaptation to nociceptive electrical stimulation as well as their link to dopaminergic neurotransmission (placebo/haloperidol). The main finding is that haloperidol changed the habituation to the absolute pain intensity over time. More precisely, in the placebo condition, activity in left postcentral gyrus and midcingulate cortex increased linearly with pain intensity only in the beginning of the experiment and subsequently habituated. In contrast, when the dopaminergic system was blocked by haloperidol, a linear increase with pain intensity was present throughout the entire experiment. Finally, there were no adaptive coding effects in any brain regions. Together, our findings provide novel insights into the nature of pain processing by suggesting that dopaminergic neurotransmission plays a specific role for the habituation to painful stimuli over time.

A Pilot Study Examining Neural Response to Pain in Adolescents With and Without Chronic Pain

“…been observed (34). Finally, in a study testing neural response to electric stimulation before and after a conditioning session (to induce habituation), the authors found a significant decrease in activation between the two session in several pain-related regions, and more importantly, found significant overall levels of deactivation in the primary somatosensory cortex and parts of the parietal cortex post-habituation (35).…”

Effects of Chronic Pain Treatment on Altered Functional and Metabolic Activities in the Brain: A Systematic Review and Meta-Analysis of Functional Neuroimaging Studies

“…Moreover, oral analgesics, one of the fastest and cheapest medications for pain treatment, are not suitable for long-term pain relief due to side effects, and patients' tolerance to opioids is increasing, which means that the dose needs to be increased over time to achieve a certain amount of pain relief (Hylands-White et al, 2017 ). Recently, chronic pain treatment, which targets neural abnormalities in patients, has been receiving more attention (Borsook et al, 2007 ; Bentley et al, 2016 ) along with the advancement of pharmacological fMRI (investigating the effects of pharmacological interventions on functional brain changes) (Duff et al, 2015 ; Bauch et al, 2017 ) and increasing efforts to search for brain markers for pain in the brain (Wager et al, 2013 ; Duff et al, 2015 ; Lopez-Sola et al, 2017 ). Although this study only covers central functional and metabolic changes in chronic patients, our approach is important for identifying neural targets for chronic pain treatment.…”

Give me a pain that I am used to: distinct habituation patterns to painful and non-painful stimulation

“…Pain habituation is commonly referred to as the adjustment to continuous or repetitive pain, resulting in a decrease in perceived pain intensity and pain-related responses. Habituation has been described repeatedly for subjective pain reports 6 – 11 and has been shown to go along with changes in electrodermal activity, reflecting autonomic responses to pain 12 , 13 . In addition, brain activity as assessed using functional magnetic resonance imaging (fMRI) has also been shown to habituate during repeated painful stimulation, predominately in cingulate, insular and somatosensory cortices 10 , 12 , 14 – 17 , even when repetition was delayed by several days 18 .…”