![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROPHARMACOLOGY
Department of Experimental Medicine, Section of Pharmacology "L. Donatelli," Second University of Naples, Naples, Italy (S.M., V.d.N., E.P., F.R.); Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy (T.B., M.V., S.P., V.D.M.); and Endocannabinoid Research Group, Institute of Cybernetics "E. Caianiello" Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy (L.C., V.G.)
In the ventrolateral periaqueductal gray (PAG), activation of excitatory output neurons projecting monosynaptically to OFF cells in the rostral ventromedial medulla (RVM) causes antinociceptive responses and is under the control of cannabinoid receptor type-1 (CB1) and vanilloid transient receptor potential vanilloid type 1 (TRPV1) receptors. We studied in healthy rats the effect of elevation of PAG endocannabinoid [anandamide and 2-arachidonoylglycerol (2-AG)] levels produced by intra-PAG injections of the inhibitor of fatty acid amide hydrolase URB597 [cyclohexylcarbamic acid-3'-carbamoyl-biphenyl-3-yl ester] on 1) nociception in the "plantar test" and 2) spontaneous and tail-flick-related activities of RVM neurons. Depending on the dose or time elapsed since administration, URB597 (0.5–2.5 nmol/rat) either suppressed or increased thermal nociception via TRPV1 or CB1 receptors, respectively. TRPV1 or cannabinoid receptor agonists capsaicin (6 nmol) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate [WIN55,212-2 (4 nmol)] also suppressed or enhanced nociception, respectively. URB597 dose dependently enhanced PAG anandamide and 2-AG levels, with probable subsequent activation of TRPV1/CB1 receptors and only CB1 receptors, respectively. The TRPV1-mediated antinociception and CB1-mediated nociception caused by URB597 correlated with enhanced or reduced activity of RVM OFF cells, suggesting that these effects occur via stimulation or inhibition of excitatory PAG output neurons, respectively. Accordingly, several ventrolateral PAG neurons were found by immunohistochemistry to coexpress TRPV1 and CB1 receptors. Finally, at the highest doses tested, URB597 (4 nmol/rat) and, as previously reported, WIN55,212-2 (25–100 nmol) also caused CB1-mediated analgesia, correlating with stimulation (possibly disinhibition) of RVM OFF cells. Thus, endocannabinoids affect the descending pathways of pain control by acting at either CB1 or TRPV1 receptors in healthy rats.
Address correspondence to: Dr. Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy. E-mail: vdimarzo{at}icmib.na.cnr.it
This article has been cited by other articles:
|
|
 |
|
  S. C. Tjen-A-Looi, P. Li, and J. C. Longhurst Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA J Appl Physiol, June 1, 2009; 106(6): 1793 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Mitchell, H. Kawahara, and C. W. Vaughan Neurotensin inhibition of GABAergic transmission via mGluR-induced endocannabinoid signalling in rat periaqueductal grey J. Physiol., June 1, 2009; 587(11): 2511 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Maione, L. Cristino, A. L. Migliozzi, A. L. Georgiou, K. Starowicz, T. E. Salt, and V. Di Marzo TRPV1 channels control synaptic plasticity in the developing superior colliculus J. Physiol., June 1, 2009; 587(11): 2521 - 2535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Maione, K. Starowicz, L. Cristino, F. Guida, E. Palazzo, L. Luongo, F. Rossi, I. Marabese, V. de Novellis, and V. Di Marzo Functional Interaction Between TRPV1 and {micro}-Opioid Receptors in the Descending Antinociceptive Pathway Activates Glutamate Transmission and Induces Analgesia J Neurophysiol, May 1, 2009; 101(5): 2411 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. McGaraughty, K. L. Chu, B. S. Brown, C. Z. Zhu, C. Zhong, S. K. Joshi, P. Honore, C. R. Faltynek, and M. F. Jarvis Contributions of Central and Peripheral TRPV1 Receptors to Mechanically Evoked and Spontaneous Firing of Spinal Neurons in Inflamed Rats J Neurophysiol, December 1, 2008; 100(6): 3158 - 3166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rubino, N. Realini, C. Castiglioni, C. Guidali, D. Vigano, E. Marras, S. Petrosino, G. Perletti, M. Maccarrone, V. Di Marzo, et al. Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex Cereb Cortex, June 1, 2008; 18(6): 1292 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Starowicz, S. Maione, L. Cristino, E. Palazzo, I. Marabese, F. Rossi, V. de Novellis, and V. Di Marzo Tonic Endovanilloid Facilitation of Glutamate Release in Brainstem Descending Antinociceptive Pathways J. Neurosci., December 12, 2007; 27(50): 13739 - 13749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Bambico, N. Katz, G. Debonnel, and G. Gobbi Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex J. Neurosci., October 24, 2007; 27(43): 11700 - 11711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Leith, A. W. Wilson, L. F. Donaldson, and B. M. Lumb Cyclooxygenase-1-Derived Prostaglandins in the Periaqueductal Gray Differentially Control C- versus A-Fiber-Evoked Spinal Nociception J. Neurosci., October 17, 2007; 27(42): 11296 - 11305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Marabese, F. Rossi, E. Palazzo, V. de Novellis, K. Starowicz, L. Cristino, D. Vita, L. Gatta, F. Guida, V. Di Marzo, et al. Periaqueductal Gray Metabotropic Glutamate Receptor Subtype 7 and 8 Mediate Opposite Effects on Amino Acid Release, Rostral Ventromedial Medulla Cell Activities, and Thermal Nociception J Neurophysiol, July 1, 2007; 98(1): 43 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xing and J. Li TRPV1 Receptor Mediates Glutamatergic Synaptic Input to Dorsolateral Periaqueductal Gray (dl-PAG) Neurons J Neurophysiol, January 1, 2007; 97(1): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Jhaveri, D. Richardson, D. A. Kendall, D. A. Barrett, and V. Chapman Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain J. Neurosci., December 20, 2006; 26(51): 13318 - 13327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Szabo, M. J. Urbanski, T. Bisogno, V. D. Marzo, A. Mendiguren, W. U. Baer, and I. Freiman Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol J. Physiol., November 15, 2006; 577(1): 263 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
