| RRC ID |
62713
|
| 著者 |
Tashima R, Koga K, Yoshikawa Y, Sekine M, Watanabe M, Tozaki-Saitoh H, Furue H, Yasaka T, Tsuda M.
|
| タイトル |
A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
A cardinal, intractable symptom of neuropathic pain is mechanical allodynia, pain caused by innocuous stimuli via low-threshold mechanoreceptors such as Aβ fibers. However, the mechanism by which Aβ fiber-derived signals are converted to pain remains incompletely understood. Here we identify a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP+) and show that specific ablation or silencing of AAV-NpyP+ SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses. AAV-NpyP+ neurons received excitatory inputs from Aβ fibers and transmitted inhibitory GABA signals to lamina I neurons projecting to the brain. In a model of neuropathic pain developed by peripheral nerve injury, AAV-NpyP+ neurons exhibited deeper resting membrane potentials, and their excitation by Aβ fibers was impaired. Conversely, chemogenetic activation of AAV-NpyP+ neurons in nerve-injured rats reversed Aβ fiber-derived neuropathic pain-like behavior that was shown to be morphine-resistant and reduced pathological neuronal activation of superficial SDH including lamina I. These findings suggest that identified inhibitory SDH interneurons that act as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavioral responses. Thus, enhancing activity of these neurons may offer a novel strategy for treating neuropathic allodynia.
|
| 巻・号 |
118(3)
|
| 公開日 |
2021-1-19
|
| DOI |
10.1073/pnas.2021220118
|
| PII |
2021220118
|
| PMID |
33431693
|
| PMC |
PMC7826356
|
| MeSH |
Animals
Hyperalgesia / genetics
Hyperalgesia / pathology
Interneurons / physiology*
Male
Mechanoreceptors / metabolism
Neuralgia / genetics*
Neuralgia / metabolism
Neuralgia / pathology
Nociception / physiology
Peripheral Nerve Injuries / genetics
Peripheral Nerve Injuries / physiopathology
Posterior Horn Cells / metabolism
Posterior Horn Cells / pathology
Protein Kinase C / genetics
Protein Kinase C / metabolism
Rats
Spinal Cord Dorsal Horn / pathology
Spinal Cord Dorsal Horn / physiology*
Touch / physiology
Touch Perception / genetics
Touch Perception / physiology*
gamma-Aminobutyric Acid / metabolism
|
| IF |
9.412
|
| リソース情報 |
| ラット |
W-Tg(Thy1-COP4/YFP*)4Jfhy (StrainID=1072) |
