التفاصيل البيبلوغرافية
| العنوان: |
Capsaicin in the periaqueductal gray induces analgesia via metabotropic glutamate receptor‐mediated endocannabinoid retrograde disinhibition |
| المؤلفون: |
Liao, H‐T, Lee, H‐J, Ho, Y‐C, Chiou, L‐C |
| المصدر: |
British Journal of Pharmacology ; volume 163, issue 2, page 330-345 ; ISSN 0007-1188 1476-5381 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2011 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
BACKGROUND AND PURPOSE Capsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1) channels, is pro‐nociceptive in the periphery but is anti‐nociceptive when administered into the ventrolateral periaqueductal gray (vlPAG), a midbrain region for initiating descending pain inhibition. Here, we investigated how activation of TRPV1 channels in the vlPAG leads to anti‐nociception. EXPERIMENTAL APPROACH We examined synaptic transmission and neuronal activity using whole‐cell recordings in vlPAG slices in vitro and hot‐plate nociceptive responses in rats after drug microinjection into the vlPAG in vivo . KEY RESULTS Capsaicin (1–10 µM) depressed evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in vlPAG slices presynaptically, while increasing miniature excitatory PSC frequency. Capsaicin‐induced eIPSC depression was antagonized by cannabinoid CB 1 and metabotropic glutamate (mGlu 5 ) receptor antagonists, and prevented by inhibiting diacylglycerol lipase (DAGL), which converts DAG into 2‐arachidonoylglycerol (2‐AG), an endocannabinoid. Capsaicin induced membrane depolarization in 2/3 neurons recorded but, overall, increased neuronal firings by increasing evoked postsynaptic potentials. Intra‐vlPAG capsaicin reduced hot‐plate responses in rats, effects blocked by CB 1 and mGlu receptor antagonists. Effects of capsaicin were antagonized by SB 366791, a TRPV1 channel antagonist. CONCLUSIONS AND IMPLICATIONS Capsaicin activated TRPV1s on glutamatergic terminals to release glutamate which activated postsynaptic mGlu 5 receptors, yielding 2‐AG from DAG by DAGL hydrolysis. 2‐AG induces retrograde inhibition (disinhibition) of GABA release via presynaptic CB 1 receptors. This disinhibition in the vlPAG leads to anti‐nociception by activating the descending pain inhibitory pathway. This is a novel TRPV1 channel‐mediated anti‐nociceptive mechanism in the brain and a new interaction between vanilloid and endocannabinoid systems. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1111/j.1476-5381.2011.01214.x |
| الإتاحة: |
https://doi.org/10.1111/j.1476-5381.2011.01214.xTest |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.E1408DAC |
| قاعدة البيانات: |
BASE |
