ACTIVATION OF SPINAL TRPV1 OR CB1 RECEPTORS IN NEUROPATHIC RATS DEPENDS ON ANANDAMIDE CONCENTRATION (Comunicazione a convegno)

Type
Label
  • ACTIVATION OF SPINAL TRPV1 OR CB1 RECEPTORS IN NEUROPATHIC RATS DEPENDS ON ANANDAMIDE CONCENTRATION (Comunicazione a convegno) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Katarzyna Starowicz, Wioletta Makuch, Fabiana Piscitelli, Stefania Petrosino, Vincenzo Di Marzo and Barbara PrzewBocka (2010)
    ACTIVATION OF SPINAL TRPV1 OR CB1 RECEPTORS IN NEUROPATHIC RATS DEPENDS ON ANANDAMIDE CONCENTRATION
    in ICRS 20th Symposium, Lund, Sweden
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Katarzyna Starowicz, Wioletta Makuch, Fabiana Piscitelli, Stefania Petrosino, Vincenzo Di Marzo and Barbara PrzewBocka (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Evidence on the relations between cannnabinoid CB1 receptors and transient receptor potential vanilloid type 1 (TRPV1) channels is accumulating. They are frequently coexpressed in neuronal cells and share at least one endogenous agonist: anandamide (AEA). However, no data are published on the potential role of spinal TRPV1 activation by AEA in neuropathic pain, and our present study was carried out to fill this gap. Rats chronically implanted with intrathecal (i.t.) catheters underwent sciatic nerve ligation (CCI model), and seven days after CCI in a time-course study mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test) were measured. We tested the effect of AEA (50 ¼g i.t.) and elevated level of endogenous AEA (following inhibition of FAAH) in CCI rats, and the involvement of TRPV1 or cannabinoid CB1 receptors in the observed effects by blocking these receptors with I-RTX (2 ¼g i.t.) or AM251 (10 ¼g i.t.), respectively. Additionally, since up-regulated spinal AEA levels may inhibit pain (as postulated by Petrosino et al., Neuropharmacology 2007) we tested if increased endogenous AEA level may change the response curve of low doses of exogenous AEA. Finally, we determined the levels of AEA in the spinal cord of CCI rats following all treatments. AEA (50 ¼g i.t.) displayed an antiallodynic and antihyperlagesic effect. The analgesic action of AEA was abolished by pretreatment with I-RTX but not AM251, suggesting the involvement of spinal TRPV1 receptors in this effect. Depending on the administered dose the selective inhibitor of AEA enzymatic hydrolysis, URB597 (10-100 ¼g i.t.), reduced thermal and tactile nociception via CB1 or CB1/TRPV1 receptors, as demonstrated by the attenuation of its effects by pretreatment with the respective antagonists, AM251 or I-RTX. When per se ineffective doses of URB597 (5 ¼g i.t.) and AEA (5 ¼g i.t.) were coadministered, a clear antinociceptive effect was observed that was abolished by pharmacological ablation of CB1 but not TRPV1 receptors. After nerve injury AEA levels were increased both in the ipsi- and contralateral side. The levels of endogenous AEA were only slightly increased by URB597 at the dose of 10 ¼g i.t., and strongly elevated by URB597 at the dose of 100 ¼g i.t. Injection of AEA (50 ¼g i.t.) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas when a lower dose was used (5 ¼g i.t.) its endogenous levels were elevated only in the presence of URB597 (5 ¼g i.t.).Consistent with the earlier observation that the concentrations required for AEA to stimulate TRPV1 are higher than those necessary for CB1 stimulation, we suggest that i.t. AEA reduces neuropathic pain by acting as an endocannabinoid or endovanilloid, depending on its concentration in the lumbar spinal cord. Up-regulation of TRPV1, such as that occurring in neuropathic pain, might regulate the functional balance between CB1 and TRPV1, although in either case AEA produces anti-hyperalgesic effects. Acknowledgements: Supported by 0152/B/2008/35, FNP and the EEA Financial Mechanism (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Dept. of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna str, 31-343 Krakow, Poland; 2 Endocannabinoid Research Group, Istituto di Chimica Biomolecolare CNR, via Campi Flegrei 34, 80078 Pozzuoli (Naples), Italy (literal)
Titolo
  • ACTIVATION OF SPINAL TRPV1 OR CB1 RECEPTORS IN NEUROPATHIC RATS DEPENDS ON ANANDAMIDE CONCENTRATION (literal)
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