The effect of nerve injury on the spinal and peripheral actions of galanin and interleukin-6 on sensory processing

Neuropathic pain, subsequent to nerve damage, is a complex condition to alleviate and leads to many chronic pain patients receiving inadequate relief from their symptoms with the current treatments available. Nerve injury results in a number of anatomical, physiological and pharmacological changes. These include an upregulation of galanin, a 29-amino acid neuropepetide, and interleukin-6 (IL-6), a neuropoietic cytokine, in the dorsal root ganglion (DRG) and in the spinal cord. The aim of this thesis is to establish what role galanin and interleukin-6 play in sensory processing spinally or in the periphery in naive and spinal nerve ligated (SNL) rats. The effects of galanin and interleukin-6 were examined in vivo and in vitro using behavioural techniques and electrophysiology to record from convergent dorsal horn neurones and single nociceptive fibres. Spinal exogenous galanin profoundly inhibited neuronal responses in SNL rats, yet facilitated the same responses in naive rats. Peripheral galanin administration inhibited responses in a majority of nociceptive C-fibres and spinal neurones and facilitated responses in the remaining fibres and neurones. Following nerve injury, the proportion of neurones inhibited by galanin was increased. Spinal IL-6 administration inhibited neuronal hyperexcitability and responses to C-fibre and mechanical stimulation in SNL rats, but had no effect in naive rats. Peripheral IL-6 administration inhibited spinal neuronal responses in vivo, heat responses of nociceptive fibres in vitro and had a behavioural anti-nociceptive effect in naive rats. In SNL rats, only spinal neuronal responses to heat were inhibited by peripheral IL-6 administration. Overall these studies show that nerve injury changes the effects of galanin and interleukin-6 and suggests these systems could be potential novel targets for the treatment of neuropathic pain