Effect of oxycodone on function of GABAA receptors in dorsal root ganglion neurons of rats with neuropathic pain

Abstract

Objective To evaluate the effect of oxycodone on function of GABAA receptors in dorsal root ganglion (DRG) neurons of rats with neuropathic pain (NP). Methods Thirty-six adult male Sprague-Dawley rats, weighing 180-220 g, aged 10 weeks, were allocated into 3 groups (n=12 each) using a random number table method: sham operation group (group S), group NP and oxycodone group (group O). The sciatic nerve was only isolated but not ligated in group S. NP was induced by chronic constriction injury.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut.Oxycodone 15 μg/kg was intraperitoneally injected once a day for 14 consecutive days from ligating the sciatic nerve to satisfaction in group O. The thermal paw withdrawal latency (TWL) was measured at 1 day before establishing the model (T0) and 3, 5, 7, 10 and 14 days after establishing the model (T1-5). The rats were sacrificed after measurement of pain threshold at T5, and DRG neurons were acutely isolated for recording the amplitude of GABAA receptors-activated currents using whole-cell patch-clamp technique. Results Compared with group S, the TWL was significantly shortened at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was decreased in NP and O groups (P<0.05). Compared with group NP, the TWL was significantly prolonged at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was increased in group O (P<0.05). Conclusion Oxycodone can enhance the function of GABAA receptors-activated currents in DRG neurons and thus enhance GABAA receptors-mediated presynaptic inhibition, which may be related to the mechanism of oxycodone-induced reduction of NP in rats. Key words: Oxycodone; Neuralgia; Ganglia, spinal; Receptors, GABA-A