Fig. 5: Anti-nociceptive effects of SM1PAG and SM1RVM relay on distinct cellar and molecular mechanisms. | Nature Communications

Fig. 5: Anti-nociceptive effects of SM1PAG and SM1RVM relay on distinct cellar and molecular mechanisms.

From: Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice

Fig. 5

a Schematic of labeling strategy. Scale bars, 200 μm. b and c Representative image showing the axon of PAGSM1 in LC (b) and RVM (c). Scale bars, 200 μm. This experiment was independently repeated 3 times from 3 mice with similar results. d Representative image showing no projection of PAGSM1 was found in the spinal cord. Scale bars, 200 μm. This experiment was independently repeated 3 times from 3 mice with similar results. e Schematic of labeling the presynaptic terminal of PAGSM1. Scale bars, 200 μm. f and g Representative image showing the synaptic boutons of PAGSM1 neurons colocalize with TH+ LC neurons (f pointed by white arrow) and TPH+ RVM neurons (g pointed by white arrow). Scale bars, Left: 100 μm, Right: 20 μm. This experiment was independently repeated 3 times from 3 mice with similar results. h Schematic of chemogenetic activation of PAGSM1 neurons. i and j Representative images of cFos immunohistochemistry in TH+ LC neurons (i P = 1.10 × 10-5) and TPH+ RVM neurons (j P = 2.97 × 10−6) after chemogenetic activation of PAGSM1 neurons. Right: percentage of neurons that colocalize with green cFos signal. Scale bars, 100 μm. k Schematic of SM1PAG or SM1RVM neurons activation combined with intrathecal administration of drugs. l Effects of activating SM1PAG neurons on CCI-induced mechanical allodynia (left, P = 7.61 × 10-5) and thermal hyperalgesia (right, P = 0.0002) after intrathecal administration of SB269970 (5-HT7 receptor antagonist), ondansetron (5-HT3 receptor antagonist), yohimbine (α2A-adrenergic receptor antagonist), naloxone (opioid receptor antagonist), and CTAP (μ opioid receptor antagonist). m Effects of activating SM1RVM neurons on CCI-induced mechanical allodynia (left, P = 4.72 × 10-7) and thermal hyperalgesia (right, P = 1.24 × 10-5) after intrathecal administration of SB269970, ondansetron, yohimbine, naloxone and CTAP. All data are expressed as mean ± sem, and (i and j) were analyzed by two-tailed unpaired t test, (l and m) were analyzed by one-way RM ANOVA test or Friedman test followed by Dunn or Dunnett’s multiple comparisons test. Sample sizes are indicated in the figures, with detailed statistics provided in Supplementary Data 1. *P ≤ 0.05, **P ≤ 0.01. Source data are provided as a Source Data file.

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