The role of the GABA-A receptor of the adjacent intact dorsal root ganglion neurons in rats with neuropathic pain

Abstract

We aim to investigate the changes of The gamma-aminobutyric acid (GABA) signals in the adjacent intact dorsal root ganglion (DRG) and the contribution of these changes to the development and maintenance of neuropathic pain (NPP). After establishment of neuropathic pain model with the lumbar 5 spinal nerve ligation (L5 SNL), the GABA-evoked currents were recorded in the acutely dissociated L4 DRG neurons using whole-cell patch clamp. Moreover, Muscimol or Bicuculline were respectively topically injected to the L4 DRG at the time of nerve injury and post-operative 5 days (POD5). The pain thresholds of hind paw were recorded. We found that the incidence and amplitude of GABA currents significantly decreased in the large and medium L4 DRG neurons after SNL (P less than 0.05). Furthermore, in the L5 SNL rats, 20 micrograms Muscimol injected immediately after injury caused a long-lasting attenuation of mechanical allodynia (P less then 0.05), whereas the thermal hyperalgesia was not alleviated (P greater than 0.05). 0.15 micrograms Bicuculline further decreased the pain thresholds (P less then 0.05) and reversed the pain-alleviating effects of Muscimol. However, at POD5, 20 micrograms Muscimol only exhibited transient alleviating effects (P less then 0.05). In conclusion, the decrease of inhibition signal mediated by GABA-A receptor in the adjacent intact DRG neurons may be crucial in the development of hyperalgesia in NPP.