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

Katharina Paul,Andreas Hahn,Georg S Kranz,Claus Lamm,Daniela M Pfabigan,Christian Windischberger,Ronald Sladky,Eva-Maria Wirth,Christoph Kraus,Nicole Geissberger,Martin Tik,Rupert Lanzenberger

doi:10.1038/s41598-021-01881-4

Abstract

Pain habituation is associated with a decrease of activation in brain areas related to pain perception. However, little is known about the specificity of these decreases to pain, as habituation has also been described for other responses like spinal reflexes and other sensory responses. Thus, it might be hypothesized that previously reported reductions in activation are not specifically related to pain habituation. For this reason, we performed a 3 T fMRI study using either painful or non-painful electrical stimulation via an electrode attached to the back of the left hand. Contrasting painful vs. non-painful stimulation revealed significant activation clusters in regions well-known to be related to pain processing, such as bilateral anterior and posterior insula, primary/secondary sensory cortices (S1/S2) and anterior midcingulate cortex (aMCC). Importantly, our results show distinct habituation patterns for painful (in aMCC) and non-painful (contralateral claustrum) stimulation, while similar habituation for both types of stimulation was identified in bilateral inferior frontal gyrus (IFG) and contralateral S2. Our findings thus distinguish a general habituation in somatosensory processing (S2) and reduced attention (IFG) from specific pain and non-pain related habituation effects where pain-specific habituation effects within the aMCC highlight a change in affective pain perception.

Highlights

Pain habituation is associated with a decrease of activation in brain areas related to pain perception
With respect to pain habituation, wide parts of the cingulate cortex seem to play a crucial role in endogenous pain c ontrol[10,12,18], which is supported by linkages to pain modulatory mechanisms like emotional state and placebo analgesia[27,28,29,30]
Significant activation was identified in regions typically associated with pain processing, including bilateral anterior and posterior insula, extending to the primary and secondary sensory cortices (S1/S2), anterior midcingulate cortex (aMCC), parts of the right thalamus and the left cerebellum (p < 0.05 FWE cluster-level corrected, see Table 1 and Fig. 2)

Summary

Introduction

Pain habituation is associated with a decrease of activation in brain areas related to pain perception. Contrasting painful vs non-painful stimulation revealed significant activation clusters in regions well-known to be related to pain processing, such as bilateral anterior and posterior insula, primary/secondary sensory cortices (S1/S2) and anterior midcingulate cortex (aMCC). Spinothalamic tract to the cerebrum, where the insula, the pregenual anterior cingulate cortex (pACC), anterior midcingulate cortex (aMCC), thalamus, prefrontal and somatosensory cortices are involved in pain perception. These brain regions are referred to as the central components of the pain m atrix[21,23,24]. With respect to pain habituation, wide parts of the cingulate cortex seem to play a crucial role in endogenous pain c ontrol[10,12,18], which is supported by linkages to pain modulatory mechanisms like emotional state and placebo analgesia[27,28,29,30]

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Conclusion