[Spinal analgesic mechanism of minocycline in formalin-induced inflammatory pain].

ABSTRACT

Objective: To investigate the spinal analgesic mechanism of minocycline in formalin-induced inflammatory pain. Methods: Behavioral test Male Sprague-Dawley rats(3-5-week old) were randomly assigned into four groups control, model, vehicle-controlled and minocycline group. Ten percent neutral formalin was injected subcutaneously into the right hind paw dorsum of the rats in model, vehicle-controlled and minocycline group. Normal saline was injected subcutaneously into the right hind paw dorsum of the rats in control group. Before 1 h of formalin injection, the rats in vehicle-controlled and minocycline group received intraperitoneal injection of saline and minocycline, respectively. Licking and lifting time was observed as the behavior results of inflammatory pain. Electrophysiologic experiment In vitro spinal cord parasagittal slices were prepared from the same rats as above. The effect of minocycline on spontaneous inhibitory postsynaptic currents(sIPSCs) of substantia gelatinosa(SG) neurons was observed using whole-cell patch-clamp technique. Results: Compared with the control group, the licking and lifting time in the model group was significantly increased. Compared with the vehicle-controlled group, the licking and lifting time in the minocycline group was significantly decreased. Minocycline significantly increased the frequency(t=9.32, P<0.05)but not the amplitude(t=1.54, P>0.05) of sIPSCs of SG neurons, the frequency of sIPSCs of control and minocycline group were (2.5±0.3)Hz and (5.2±0.6)Hz, respectively. When calcium was removed from the extracellular solution, the frequency before and after minocycline perfusion were (0.9±0.1)Hz and (0.9±0.1)Hz, respectively, the amplitude before and after minocycline perfusion were (18.2±0.7)pA and (18.5± 0.6)pA, respectively, the difference of frequency or amplitude was not statistically significant(t=0.32, 0.82, all P>0.05). However, minocycline still increased the frequency of sIPSCs when glutamate receptor antagonists 6-Cyano-7-nitroquinoxaline-2, 3-dione(CNQX) and D-(-)-2-Amino-5-phosphonopentanoic acid(APV) were included in extracellular solution(t=13.51, P<0.05), the frequency of sIPSCs were (2.0±0.1)Hz and (4.3±0.4)Hz, respectively. Minocycline still increased the frequency of IPSCs when voltage-gated sodium channel blocker tetrodotoxin(TTX) were included in extracellular solution(t=8.67, P<0.05), the frequency of IPSCs were (2.2±0.2)Hz and (5.2±0.5)Hz. Conclusion: Minocycline can attenuate formalin-induced inflammatory pain which may be associated with its increase in the inhibitory synaptic transmission of SG neurons.