The characterisation of myelinated and unmyelinated afferents in normal and neuropathic pain

Funding: Pain Relief Foundation

Neuropathic pain (NP) can be caused or triggered by a primary lesion or dysfunction in the peripheral nervous system.  In NP states touch that would normally be innocuous is felt as painful (allodynia), and experimental evidence, largely based upon selective nerve block, suggests this phenomenon may be mediated in humans through heterosynaptic central sensitization.  However, to date no published data exist about the normality or otherwise of mechanosensitive A-beta function and therefore the potential for a contribution of abnormal firing in otherwise ‘normal’ nerves cannot be excluded. Also, the recently discovered unmyelinated CT afferent mechanoreceptor system has also been implicated in neuropathic pain and allodynia. These fibres, only found in hairy skin, respond preferentially to slow gentle brush stimuli (similar to stimuli which evoke allodynia) and are posited to play a role in affective touch. Animal and human studies suggest these afferents contribute to allodynia in experimental pain.  A recent study investigating an experimental model of allodynia in patients lacking large A-beta fibres suggests that in allodynic states CT afferents lose their ability to signal pleasant touch. Controlled studies investigating the role of either A-beta or CT mechanosensitive afferents, or their signalling, in neuropathic pain syndromes are lacking. Given that CTs are not present in glabrous skin there may also be interesting qualitative differences in allodynia when compared to hairy skin. Detailed assessment of the psychophysical differences in neuropathic pain between hairy and glabrous skin have not been performed.

The PhD project has three objectives: i) training in microneurography, ii) developing intraneural microstimulation and psychophysical procedures using normal participants coupled with experimental pain manipulations, iii) characterising peripheral nerve fibre function in neuropathic pain patients.

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