Article Figures & Data
Figures
- Figure 1.
Experimental setup. Three skull openings (red ovals) were made. A small burr hole was made over the left frontal cortex to elicit CSD events using a pinprick (PP). Meningeal afferent activity was recorded in the left trigeminal ganglion (TG) using a tungsten microelectrode inserted through a craniotomy made over the contralateral hemisphere. An ipsilateral craniotomy was made to expose a part of the left transverse sinus (TS) and its vicinity to search for meningeal afferents with mechanical RF. Quantitative mechanical stimuli were delivered to the afferents’ RF using a feedback-controlled mechanical stimulator. Laser Doppler flowmetry (LDF) probe was placed over the cortex near the stimulated afferent’s RF to validate the induction of the CSD by testing related changes in cerebral blood flow. SSS, superior sagittal sinus.
- Figure 2.
An example showing the development of mechanical sensitization after CSD in one C-unit meningeal afferent unit. A, Top, trace examples of mechanically evoked afferent discharge to TH and STH stimuli during the last baseline stimuli trial, before the induction of CSD, and during the trials conducted at 15, 90, and 240 min after the induction of CSD. Below are matching peristimulus time histograms (PSTH, bean size 0.5 s) with mechanically evoked responses (spikes/s) in parentheses. The bottom trace illustrates the CBF at baseline and during the post-CSD mechanical stimulation trials. The insert denotes the acute changes in CBF during the arrival of the CSD near the RF of the recorded afferent. Note the CSD-evoked increase (red) and decrease (blue) in CBF. Also note the reduced CBF (blue traces) present at 15 and 90 min after the onset of CSD. B, Time course data depicting the level of ongoing activity, TH and STH responses of the same unit during baseline sampling and every 15 min after the induction of CSD.
- Figure 3.
Summary of characteristics of the mechanical sensitization induced after the elicitation of CSD in the frontal cortex. TH (A) and STH (B) responses in neurons that exhibited mechanical sensitization. Data depict the mean responses at baseline, before CSD, and during the time of peak response after CSD (range 30–135 min). C, Mean ± 95% CI of the latency to onset of persistent sensitization. D, Duration of persistent sensitization. The means, indicated by circles (± 95% CI), reflect data from afferents in which CSD-evoked changes in mechanical responsiveness were studied for up to 90 min (n = 13). The durations of sensitization of units in which post-CSD responses were recorded for up to 240 min (n = 4) are indicated by asterisks. (E) Mean ± 95% CI of the magnitude increase in neuronal responses to TH and STH mechanical stimuli.
- Figure 4.
Mechanical sensitization of meningeal afferents induced after CSD is not correlated with the post-CSD increase in afferents’ ongoing activity. Pearson’s correlation indicated no linear relationship between the latency to onset of the sensitization and that of the increase in ongoing activity (A, B). There was no significant correlation between the duration of the sensitization response and the duration of the increase in ongoing activity (C, D). The magnitude of mechanical sensitization post-CSD was also not correlated with the magnitude of the increase in ongoing activity rate (E, F).
Tables
Line Data structure Type of test Power of 25-75% Confidence interval a Normality test: passed (p > 0.99); Equal variance test: failed (p < 0.05) Mann–Whitney rank-sum test 25–75% non–sensitized: 0.31–0.95; sensitized: 0.16–0.5 b Normality test: passed (p > 0.99); Equal variance test: passed (p = 0.5) Unpaired t test p = 0.66 c Normality test: passed (p = 0.18); Equal variance test: failed (p < 0.05) Mann–Whitney rank-sum test 25–75% non–sensitized: 0.01–0.155; sensitized: 0.05–0.84 d Normality test: passed (p > 0.99); Equal variance test: passed (p = 0.08) Unpaired t test p = 0.77 e Normality test: passed (p > 0.99); Equal variance test: passed (p = 0.75) Unpaired t test p = 0.87 f Normality test: passed (p = 0.09); Equal variance test: passed (p = 0.58) Unpaired t test p = 0.77 g Normality test: passed (p = 0.66); Equal variance test: passed (p = 0.98) Unpaired t test p = 0.38 h Normality test: passed (p > 0.99); Equal variance test: passed (p = 0.57) Unpaired t test p = 0.28 i Normality test: passed (p = 0.8); Equal variance test: passed (p = 0.67) Unpaired t test p = 0.69 j Normality test: passed (p = 0.84); Equal variance test: failed (p < 0.05) Mann–Whitney rank-sum test 25–75% Aδ: 0.45–2.32; C: 0.67–4.13 k Normality test: passed (p = 0.11); Equal variance test: failed (p < 0.05) Mann–Whitney rank-sum test 25–75% TH: 0.51–2.64; STH: 1.33–1.77 l Normality test: passed (p = 0.06); Equal variance test: failed (p < 0.05) Mann–Whitney rank-sum test 25–75% Aδ: 1.29–1.39; C: 1.41–1.83 m Normality test: passed (p = 0.1); Equal variance test: passed (p = 0.75) Pearson’s correlation coefficient test p = 0.99 n Normality test: passed (p = 0.08); Equal variance test: passed (p = 0.46) Pearson’s correlation coefficient test p = 0.99 o Normality test: failed (p < 0.05); Equal variance test: failed (p < 0.05) Spearman’s correlation test 25–75% activation: 1.46–4.25; TH: see k p Normality test: failed (p = 0.06); Equal variance test: failed (p < 0.05) Spearman’s correlation test 25–75% activation: see o; STH: 1.33–1.64 q Normality test: failed (p < 0.05); Equal variance test: failed (p < 0.05) Spearman’s correlation test 25–75% activation: 17–40; TH: 30–90 r Normality test: failed (p < 0.05); Equal variance test: passed (p = 0.1) Pearson’s correlation coefficient test p = 0.99 - Table 2.
Response properties of meningeal afferents that developed and did not develop mechanical sensitization following CSD
Sensitization n Baseline threshold (g) Identified RFs Baseline ongoing activity (Hz) Sensitized 17 0.5 ± 0.2a 2.1 ± 0.3b 0.4 ± 0.1c Nonsensitized 6 0.5 ± 0.2 2.0 ± 0.3 0.6 ± 0.3 Data show the mean ± SEM. (a–c) Two-tailed unpaired t-test revealed no significance differences between the groups.
- Table 3.
Rate of different types of mechanical sensitization responses in Aδ and C meningeal afferents following CSD
Group TH only STH only TH + STH Aδ C Aδ C Aδ C CSD 2/9 (11) 1/14 (7) 2/9 (22) 2/14 (14) 3/9 (30) 7/14 (50) Control 0/5 (0) 1/7 (8) 0/5 (0) 0/7 (0) 0/5 (0) 0/7 (0) Data show rate (% of responses). Sensitization at the TH and STH levels were determined according to the calculation described in the Methods. Two-tailed χ2 tests revealed no significant differences in the rate of the sensitization responses exhibited by the Aδ and C-unit populations.
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