| Background and Objectives1. The drawbacks of intensive pesticide use, such as pesticide residues, have attractedgreat attention from the society. As we know, most insecticides are neurotoxic.Knowledge of neurological effects of low-level pesticide exposure on human healthmay help farmers to make more appropriate decisions regarding pesticide use, andhas implications for making decision on agricultural regulations. We aimed toevaluate the peripheral neurological effects of pesticide use among farmers in China,and further investigate into the mechanisms underlying the effects of cypermethrinon the sensory nerve conduction.2. Prediabets/early diabetes-associated neuropathy is characterized by prominentsmall-fiber injury. The abnormal IENFD is the gold standard for diagnosis of smallfiber neuropathy. Our aim is to summarize the clinical, electrophysiological, andneuropathological characteristics of prediabetic neuropathy.Methods1. A cohort of246farmers was randomly selected from3provinces (Guangdong,Jiangxi, and Hebei) in China. Two rounds of questionnaire interview, neurologicalexamination, and NCS were conducted. Multivariate regression models and FEmodels were used to evaluate the short-term and long-term effects of pesticides onthe peripheral nervous system.2. The whole-cell voltage-clamp was used to elucidate the effects of cypermethrin useon the sodium channels in acutely dissociated rat DRG neurons.3.20consecutive patients diagnosed with sensory or autonomic polyneuropathy wereenrolled in the study. Patients were divided into prediabetes/early diabetes group (n=10) and other etiology group (n=10). The results of clinical materials, NCS andIENFD were statistically analyzed.ResultsPart One1. Logistic analysis showed that farmers exposed to high-level pesticide had greaterrisk of developing sensation of numbness or prickling (odds ratio (OR)2.62,95% confidence interval (CI):1.08–6.36). Female gender (OR4.48,95%CI:1.66–12.10)and exposure to neurotoxic substances (OR8.13,95%CI:1.06–62.07) alsoincreased the risk of developing the symptom.2. Logistic regression analysis showed that impairment of vibration sensation had anOR>2(OR2.49,95%CI0.83–7.47), however, this did not reach statisticalsignificance.Part Two1. OLS models showed that farmers with higher level of pesticide exposure had lowertibial nerve proximal and distal CMAP amplitude in the long term.2. In Dprobit models, long-term pesticide use increased the abnormalities of SCV andSNAP in all tested nerves.3. The results of FE models indicated that conduction velocities (median motor, ulnarmotor, and ulnar sensory) were significantly increased, while the amplitudes ofCMAP (median, ulnar, tibial, peroneal) and SNAP (median, ulnar) were decreased,and DML (ulnar, tibial) were shortened shortly after exposure. These effectsoccurred earlier in nerves from upper limb than in those from lower limb.4. In short-term, organosulfur and pyrethroid decreased the SNAP amplitudes (median,ulnar); organic nitrogen decreased the ulnar CMAP amplitude and tibial MCV;organophosphates decreased the tibial MCV, and prolonged the ulnar DML.5. In medium-term, neonicotinoid decreased the peroneal proximal CMAP amplitude.Part Three1. Na+currents of DRG neuron were inhibited by cypermethrin in a concentration-,frequency-and time-dependant way.2. The study of gating mechanism found that the half-activation potential shiftedpositively, while the half-inactivation potential shifted negatively after exposure tocypermethrin. The recovery procedure from inactivation was accelerated withcypermethrin.3. The kinetics of sodium channel showed that the time constant of activation andinactivation were both prolonged by cypermethrin.Part Four1. The patients in prediabetes/early diabetes group had lower IENFD than those inother etiolgoy group (P=0.04).2. Multivariate linear regression analyses showed that IENFD was positively correlated with peroneal motor, tibial motor and sural conduction velocities inprediabetes/early diabetes-associated neuropathy (P <0.05).Conclusions1. Long-term low-level pesticide exposure may increase the risk of developingneurological symptoms among farmers, with the somatosensory small fibers mostlikely to be affected.2. Low-level pesticide exposure can cause extensive acute subclinical NCS changes.3. Different types of pesticides have different effects on action potential amplitude,conduction velocity and DML.4. The medium-and long-term uses of low-level pesticide predominantly decrease theaction potential amplitudes in lower limb, which indicate length-dependant axonalinjury.5. Cypermethrin inhibited total Na+currents by changing the gating and kineticsproperties of the voltage-gated sodium channels, and eventally decreased theamplitude of compound action potential.6. In our study, the proportion of prediabetes/early diabetes in otherwise idiopathicneuropathy is60%. The prediabetes/early diabetes-associated neuropathy may causesmall-fiber loss, as well as large fiber injury. |
