| RRC ID |
89271
|
| 著者 |
Ishibashi T, Sueto D, Yoshikawa Y, Koga K, Yamaura K, Tsuda M.
|
| タイトル |
Identification of Spinal Inhibitory Interneurons Required for Attenuating Effect of Duloxetine on Neuropathic Allodynia-like Signs in Rats.
|
| ジャーナル |
Cells
|
| Abstract |
Neuropathic pain is a chronic pain condition that occurs after nerve damage; allodynia, which refers to pain caused by generally innocuous stimuli, is a hallmark symptom. Although allodynia is often resistant to analgesics, the antidepressant duloxetine has been used as an effective therapeutic option. Duloxetine increases spinal noradrenaline (NA) levels by inhibiting its transporter at NAergic terminals in the spinal dorsal horn (SDH), which has been proposed to contribute to its pain-relieving effect. However, the mechanism through which duloxetine suppresses neuropathic allodynia remains unclear. Here, we identified an SDH inhibitory interneuron subset (captured by adeno-associated viral (AAV) vectors incorporating a rat neuropeptide Y promoter; AAV-NpyP+ neurons) that is mostly depolarized by NA. Furthermore, this excitatory effect was suppressed by pharmacological blockade or genetic knockdown of α1B-adrenoceptors (ARs) in AAV-NpyP+ SDH neurons. We found that duloxetine suppressed Aβ fiber-mediated allodynia-like behavioral responses after nerve injury and that this effect was not observed in AAV-NpyP+ SDH neuron-selective α1B-AR-knockdown. These results indicate that α1B-AR and AAV-NpyP+ neurons are critical targets for spinal NA and are necessary for the therapeutic effect of duloxetine on neuropathic pain, which can support the development of novel analgesics.
|
| 巻・号 |
11(24)
|
| 公開日 |
2022-12-14
|
| DOI |
10.3390/cells11244051
|
| PII |
cells11244051
|
| PMID |
36552814
|
| PMC |
PMC9777279
|
| MeSH |
Analgesics / pharmacology
Analgesics / therapeutic use
Animals
Duloxetine Hydrochloride / pharmacology
Duloxetine Hydrochloride / therapeutic use
Hyperalgesia* / complications
Interneurons
Neuralgia* / drug therapy
Neuralgia* / etiology
Rats
|
| リソース情報 |
| ラット |
W-Tg(Thy1-COP4/YFP*)4Jfhy (StrainID=1072) |
