Background & Aims

Gentle touch is a unique sensory modality capable of evoking strong negative and positive emotions depending on factors such as environmental context and internal physiological states.1
Dysregulation of gentle touch processing is a hallmark of many disorders including chronic pain where gentle touch becomes painful and aversive. Sensory neurons expressing MrgprB4 detect gentle stroking in mice. Activation of these neurons is known to be positively reinforcing.2,3 This project uses optogenetics, behavioral techniques and immunohistochemistry to assess whether activation of channelrhodopsin (ChR2) expressing MrgprB4 afferents signal positively valenced tactile information, whether this is altered in chronic pain and whether this is reflected in the downstream circuits recruited.

Methods

A ceramic ferrule was surgically implanted in the lumbar vertebrae of mice expressing ChR2 in MrgprB4+ afferents (MrgprB4-ChR2) to deliver blue light to the central projections of the primary afferents. We used a real-time place preference (RTPP) paradigm with optogenetics to assess the motivational properties of blue light stimulation in implanted male and female MrgprB4-ChR2 mice that had either undergone a spared nerve injury (SNI) or a sham surgery and assessed whether gabapentin administration affected the response. All mice underwent a final stimulation protocol after which the brains, spinal cords and dorsal root ganglions of the mice were dissected out for immunohistochemical analysis.

Results

Light stimulation in one arm of the assay increased preference for that arm in the male and female sham surgery mice but not the SNI animals. Preference for blue light could be partially restored in the male SNI mice through treatment with gabapentin. Preliminary results from the immunohistochemistry experiments also show that stimulation successfully induced c-fos expression in the spinal dorsal horn of the stimulated animals and this expression was predominantly found in the superficial dorsal horn of the spinal cord, consistent with the innervation pattern of the MrgprB4+ afferents. Whole brain c-fos results also showed differential recruitment of brain regions following optogenetic activation of MrgprB4+ fibers in sham and nerve injured mice.

Conclusions

In conclusion, the motivational value associated with gentle touch is plastic and can be abated in models of chronic pain. Future work will continue to elucidate the subtypes of spinal dorsal horn neurons recruited and the specific brain regions activated in the processing and perception of gentle touch both in chronic pain and in control conditions.

References

1. Ellingsen, D. M., Leknes, S., Loseth, G., Wessberg, J. & Olausson, H. The Neurobiology Shaping Affective Touch: Expectation, Motivation, and Meaning in the Multisensory Context. Front Psychol 6, 1986 (2015). https://doi.org:10.3389/fpsyg.2015.01986
2. Vrontou, S., Wong, A. M., Rau, K. K., Koerber, H. R. & Anderson, D. J. Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo. Nature 493, 669-673 (2013). https://doi.org:10.1038/nature11810
3. Elias, L. J. et al. Touch neurons underlying dopaminergic pleasurable touch and sexual receptivity. Cell 186, 577-590 e516 (2023). https://doi.org:10.1016/j.cell.2022.12.034

Presenting Author

Maham Zain

Poster Authors

Maham Zain

BSc

University of Toronto

Lead Author

E-mail

Laura Bennett

University of Toronto

Lead Author

E-mail

Quinn Pauli

BSc

University of Toronto

Lead Author

E-mail

Juliet Arsenault

Lead Author

E-mail

Jenny Cheung

BSc

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toront

Lead Author

E-mail

Hantao Zhang

BSc

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toront

Lead Author

E-mail

Robert P. Bonin

Lead Author

Topics

  • Mechanisms: Biological-Molecular and Cell Biology