Defining the contribution of C-fibre low threshold mechanoreceptors to nociception, acute pain and pain chronicity

A population of peripheral sensory neurons termed C-tactile fibres in humans and C-low threshold mechanoreceptors (C-LTMR) in animals have been demonstrated to be responsible for emotive aspects of pleasant, affiliative touch under normal conditions.

Dorsal root ganglia section showing putative C-LTMRs in green and myelinated neurons in red
Dorsal root ganglia section showing putative C-LTMRs in green
and myelinated neurons in red

 More recently it has been suggested that these neurons may also play a paradoxical role after injury and contribute to pain sensation. This hypothesis stems from the observation that the same light brushing stimuli which preferentially activate C-tactile/C-LTMRs units under basal conditions, evoke allodynia in pathological pain conditions. However, the precise role of these fibres in triggering pain sensation is controversial; while some studies have demonstrated that blocking the activity of these neurons reduces mechanical allodynia after injury, others have postulated that these neurons exert an inhibitory influence on pain processing and that loss of function upon injury reverses this inhibitory control.

Studies on the role of C-tactile/C-LTMR fibres in pain sensation have been complicated by a lack of specific molecular markers for these populations and an absence of tools with which to study their function in vivo. Moreover, it has recently become apparent that there may be different subsets of C-LTMR with non-overlapping molecular profiles.

Staining of the skin showing <br> a highly arborized putative C-LTMR
Staining of the skin showing
a highly arborized putative C-LTMR

  In this proposal we have generated molecular tools with which to selectively manipulate C-LTMR subtypes in order to determine their relative contribution to nociception and pain chronicity. By experimentally silencing or activating these neurons in mice we aim to uncover the role they play in nociceptive processing and understand how they transition from detecting pleasure to pain.a

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