Preventive Effect Of Gabapentin On Peripheral Nerve Injury Induced By Bortezomib

ObjectiveExplore the effects of gabapentin on peripheral neuropathy caused by bortezomib through animal experiments,as well as the serum levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).The expression of some factors in the Nuclear factor-κB(NF-κB)signaling pathway in the root ganglia(DRG),and to explore the mechanism of gabapentin in preventing and treating peripheral nerve injury caused by bortezomib.Methods48 male SD rats were randomly divided into 4 groups,each with 12 rats,which were set as blank control group(NS group),model control group(BTZ group),normal dose group(GBPN group),and high dose group(GBPH group),were given normal saline(NS group),bortezomib(BTZ group),bortezomib +normal dose gabapentin(GBPN group),bortezomib + high dose gabapentin(GBPH group),observe the rats The difference in overall condition,activity,heat pain response before and after the drug,and the changes of the sciatic nerve under light microscope after the drug,enzyme-linked immunoassay(ELISA)to determine serum TNF-α and IL-6 changes and protein immunoassay(Western blot)to determine the expression levels of some factors in the NF-κB signaling pathway in the spinal DRG.Results(1)Overall condition: mainly manifested in three aspects: foraging,diarrhea and body weight.The NS group had normal foraging,no diarrhea,and normal weight gain.The foraging activity of the BTZ group was weakened,some rats had diarrhea,and the body weight increased more slowly than that of the NS group and even decreased.The difference was statistically significant(P<0.05).The GBPN group’s foraging activities were basically normal,occasionally diarrhea,and the weight gain was basically normal.Compared with the BTZ group,the difference was statistically significant(P<0.05).The foraging activity of GBPH group was basically normal,but slightly worse than that of the GBPN group,occasionally had diarrhea,and weight gain was slower than that of the GBPN group and the NS group(P<0.05).(2)Activity change and anxiety state: It is evaluated by two aspects: usual observation and open field experiment.It was observed that the BTZ group had a significant decrease in activity a few hours after the bortezomib injection compared with other groups.The results of the open field experiment showed that the average speed and total distance of the BTZ group were significantly higher or lower than those of the other groups.The difference was statistically significant(P<0.05).The difference between the other groups was not significant,and the difference was not statistically significant.Significance(P>0.05).(3)Heat pain reaction: The results of the hot plate experiment showed that the heat pain reaction time of the BTZ group was significantly shorter than that of the NS group(P<0.05),while the difference between the GBPN group and the GBPH group and the NS group was not statistically significant(P>0.05).There was a statistically significant difference between the BTZ group and the GBPN group and the GBPH group(P<0.05).(4)Histomorphological changes: Observed under light microscope,the nerve fibers in the BTZ group were obviously swollen,thickened,and the myelin sheath was deformed.Compared with the GBPH group,the nerve damage in the GBPN group was slightly less,but at the same time,the damage was less than in the BTZ group.(5)Changes of serum inflammatory factors: There was no significant difference among groups before administration(P>0.05).After administration,the levels of TNF-α and IL-6 in serum of BTZ group were significantly higher than those of NS group(P<0.05).Compared with BTZ group,the content of IL-6 in GBPN group and GBPH group decreased significantly(P<0.05).The content of TNF-α in GBPN group decreased significantly(P<0.05),but there was no significant difference between GBPH group and BTZ group(P>0.05).(6)Changes of some factors in the NF-κB pathway in the dorsal root ganglia(DRG)of the spinal cord: Compared with the other three groups,the concentration of IKBα protein in the BTZ group was significantly increased,and the two factor protein concentrations of IKKβ and p65 were significantly reduced.The difference was statistically significant(P<0.01).However,the difference between the other three groups was not statistically significant(P>0.05).Conclusions(1)A certain amount of gabapentin can effectively improve the peripheral neuropathy caused by bortezomib,but if the amount exceeds a certain level,the therapeutic effect may be unchanged or worse.(2)Gabapentin affects the levels of serum TNF-α and IL-6 to a certain extent,thereby alleviating peripheral neuropathy.(3)Gabapentin may mediate the expression of related proteins in the spinal dorsal root ganglion(DRG)NF-κB signaling pathway to a certain extent,promote the survival of nerves,and reduce pain.