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Sex dependent regulation of C fibre pain neurotransmission

The basic currency of communication in the nervous system is the action potential. As the action potential is an all-or-none event, information is coded by the number of action potentials and the time intervals between them.

In the pain system the intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibres to the spinal cord (Torebjork et al. 1984). C fibres conduct successive action potentials at progressively slower speeds (Serra et al. 1999; Thalhammer et al. 1994) but the impact of this activity-dependent slowing (ADS) upon spinal pain processing is unknown. We have data from the laboratory demonstrating a reduction in ADS in preclinical pain models that reduces the intervals between pain inputs arriving at spinal neurons. This could provide a peripheral mechanism to amplify spinal nociceptive processing and promote enhanced pain sensation termed ‘hyperalgesia’. Notably this change in ADS is sex dependent which is of interest given increasing awareness of sex differences in clinical pain syndromes (Mogil 2012).

This project will investigate 1) the mechanisms underlying altered ADS in preclinical pain models using biochemical and pharmacological approaches 2) the impact of this altered ADS upon spinal pain processing at the both the single neuron and network level using patch clamp and field potential electrophysiological recording, respectively, in ex vivo spinal preparations and 3) the impact of ADS upon the processing of natural noxious stimuli using extracellular recording in vivo.

This work will further our understanding of sex dependent altered C fibre function in preclinical models and determine whether ADS provides a peripheral mechanism that can regulate spinal pain processing and pain sensation.

Torebjork HE, LaMotte RH, Robinson CJ (1984) Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: simultaneous recordings in humans of sensory judgments of pain and evoked responses in nociceptors with C-fibers. Journal of neurophysiology 51:325-339.

Serra J, Campero M, Ochoa J, Bostock H (1999) Activity-dependent slowing of conduction differentiates functional subtypes of C fibres innervating human skin. J Physiol 515 ( Pt 3):799-811.

Thalhammer JG, Raymond SA, Popitz-Bergez FA, Strichartz GR (1994) Modality-dependent modulation of conduction by impulse activity in functionally characterized single cutaneous afferents in the rat. Somatosens Mot Res 11:243-257.

Mogil JS (2012) Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. NatRevNeurosci 13:859-866.

Primary supervisor

Dr Carole Torsney

Dr Carole Torsney lab

 +44 (0)131 650 9881

Carole.Torsney@ed.ac.uk

Second supervisor

Prof Mike Ludwig

Further information

Centre for Integrative Physiology website