Deciphering migraine pain mechanisms through electrophysiological insights of trigeminal ganglion neurons.

Migraine is a complex neurological disorder that affects millions of people worldwide. Despite extensive research, the underlying mechanisms that drive migraine pain and related abnormal sensation symptoms, such as hyperalgesia, allodynia, hyperesthesia, and paresthesia, remain poorly understood. One of the proposed mechanisms is cortical spreading depression (CSD), which is believed to be involved in the regulation of trigeminovascular pathways by sensitizing the pain pathway. Another mechanism is serotonin depletion, which is implicated in many neurological disorders and has been shown to exacerbate CSD-evoked pain at the cortical level. However, the effects of CSD and serotonin depletion on trigeminal ganglion neurons, which play a critical role in pain signal transmission, have not been thoroughly studied. In this study, we aimed to investigate the association between CSD and serotonin depletion with peripheral sensitization processes in nociceptive small-to-medium (SM) and large (L) -sized trigeminal ganglion neurons at the electrophysiological level using rat models. We divided the rats into four groups: the control group, the CSD group, the serotonin depletion group, and the CSD/serotonin depletion group. We induced CSD by placing KCl on a burr hole and serotonin depletion by intraperitoneal injection of PCPA (para-chlorophenoxyacetic acid). We then isolated trigeminal ganglion neurons from all groups and classified them according to size. Using patch-clamp recording, we recorded the excitability parameters and action potential (AP) properties of the collected neurons. Our results showed that in SM-sized trigeminal ganglion neurons, the CSD-SM and CSD/serotonin depletion groups had a higher positive resting membrane potential (RMP) than the control-SM group (p = 0.001 and p = 0.002, respectively, post-hoc Tukey's test). In addition, the gap between RMP and threshold in the CSD-SM group was significantly narrower than in the control-SM group (p = 0.043, post-hoc Tukey's test). For L-sized neurons, we observed prolongation of the AP rising time, AP falling time, and AP duration in neurons affected by CSD (p < 0.05, pairwise comparison test). In conclusion, our study provides new insights into the underlying mechanisms of migraine pain and abnormal somatosensation. CSD and serotonin depletion promote the transmission of pain signals through the peripheral sensitization process of nociceptive small-to-medium-sized trigeminal ganglion neurons, as well as nociceptive and non-nociceptive large-sized trigeminal ganglion neurons.

Quantifying altered long-term potentiation in the CA1 hippocampus.

Long-term potentiation (LTP) of synaptic transmission is a widely accepted model of learning and memory. In vitro brain slice techniques were used to investigate the effects of cortical-spreading depression and picrotoxin, an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, on the tetanus-induced long-term potentiation of field excitatory postsynaptic potentials. Cortical-spreading depression is involved in glutamate desensitization; on the other hand, GABA(A) antagonists could increase postsynaptic excitability. This study shows that picrotoxin effectively induced long-term potentiation with 142.25 ± 4.18% of the baseline in the picrotoxin group (n = 8) versus 134.36 ± 2.35% of the baseline in the control group (n = 10). In group with picrotoxin applied to CSD, we obtained the smallest magnitude of LTP (120.15 ± 3.73% of the baseline, n = 8). These results suggest that picrotoxin could increase hippocampal activity and LTP; on the contrary, CSD reduced LTP magnitude. In addition, the results also suggest that the decay rate of post-tetanic potentiation has a direct relationship with LTP. Moreover, data were interpreted by nonlinear least squares quantifying, and LTP could also be quantified. The nonlinear attribute of LTP had an influence on the fitting, with respect to increasing the accuracy of the parameters and the compatibility of combination of stimuli that produce LTP.