Role of Glycinergic Neurotransmission in Neuropathic Pain

Abstract

The Gate Control Theory of Pain highlights an interconnected network of myelinated and unmyelinated fibres within the dorsal horn (Melzack & Wall, 1965). Currently there are a number of proposed theories to explain the mechanism by which pain is developed, one of which is the theory of disinhibition whereby a reduction of inhibitory neurotransmission leads to over-excitation within the central nervous system (Guo & Hu, 2014; Zeilhofer, 2005). Evidence within my supervisor’s laboratory has identified glycinergic inhibitory neurotransmission to be a key component in the development of neuropathic pain. This study aimed to identify the main reasons for these reductions in inhibitory neurotransmission shown within lamina II of the dorsal horn. It is hypothesised that inhibitory neurotransmission is lost following injury leading to over-excitation within the dorsal horn. The experiments performed within this study were optimised through following vigorous testing procedures often requiring multiple trial and error attempts prior to the development of both valid and reliable results. PKCγ immunoreactive neurons are found within lamina II of the dorsal horn are classified into distinct morphological categories, and are involved in the filtering of nociceptive and mechanical input (Martin, Liu, Wang, Malmberg & Basbaum, 1999). This study showed distinct changes of PKCγ immunoreactive neurons following a neuropathic pain injury suggestive of the possibility of changes to the neural circuitry within the dorsal horn. Furthermore GAD67 neurons in lamina II of the dorsal horn was analysed to identify whether this can be used as a method of identifying changes in presynaptic neurons following neuropathic injury but failed to yield significant results. In conclusion immunohistological studies are found to be limited in providing physiological information on neurons within the dorsal horn. As a result future experimentations seeking alternative techniques must be sought to confirm the significance the results in the study.