Few studies have examined how nerve injury alters GABAA receptors expressed by primary afferent neurons. Yet, changes in these receptors may contribute to the allodynia, hyperalgesia, and spontaneous pain that develop after nerve injury. This proposal will characterize the molecular composition, distribution, and physiological properties of GABAA receptors expressed by dorsal root ganglion (DRG) neurons. It will also determine these changes in the injured L5 and uninjured L4 DRG after L5 spinal nerve ligation. The latter issue is of interest because the activity of uninjured neurons in the L4 DRG is altered as a consequence of these afferents intermingling with injured L5 afferents undergoing Wallerian degeneration in the peripheral nerve. Western blot analysis will determine the levels and subunit composition of GABAA receptors in the L4 and L5 DRG of naive, sham, and ligated rats as a function of time after injury. Fluorescence immunohistochemistry will characterize the distribution of GABAA receptor subunits relative to populations of immunohistochemically- identified DRG neurons. Whole-cell voltage clamp recordings of acutely dissociated DRG neurons will pharmacologically characterize GABAA receptors. These results will provide new insights into the molecular and neuroanatomical bases of inhibitory synaptic transmission in the spinal cord before and after nerve injury. Understanding how presynaptic inhibitory mechanisms in the spinal cord change after nerve injury can guide the development of new pharmacological treatments for the relief of neuropathic pain.
| Aldrich, B T; Frakes, E P; Kasuya, J et al. (2009) Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation. Neuroscience 164:711-23 |
