Hyperbaric Oxygen Treatment at Various Stages following Chronic Constriction Injury Produces Different Antinociceptive Effects via Regulation of P2X4R Expression and Apoptosis

PurposeThe aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlyingmechanisms of HBO treatment.MethodsForty adult male Sprague—Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group.Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postop erative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemis try and western blot analysis. Cell apoptosis was measured using TUNEL staining. The ex pression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes.ResultsEarly HBO treatment beginning on postoperative day 1 produced a persistent antinocicep tive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postopera tive day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apopto sis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatmentbeginning on postoperative day 6 produced a transient antinociceptive effect without chang ing the expression of P2X4R or CCI-induced apoptosis.ConclusionHBO treatment at various stages following CCI can produce antinociceptive effects via dif ferent mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression,and late HBO treatment is associated with inhibition of cell apoptosis.