The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats
نویسندگان
چکیده
BACKGROUND Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. RESULTS The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. CONCLUSION These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.
منابع مشابه
Endocannabinoid System and TRPV1 Receptors in the Dorsal Hippocampus of the Rats Modulate Anxiety-like Behaviors
Objective(s) Fatty acid is amide hydrolase which reduce endogenous anandamide. Transient receptor potential vanilloid-1 (TRPV1) channels have been reported to have a role in the modulation of anxiety-like behaviors in rodents. In the present study, the effects of either endocannabinoid system or TRPV1 channels and their possible interaction on anxiety-like behaviors of the rats were explored. ...
متن کاملProgress in Neuro-Psychopharmacology & Biological Psychiatry Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: Additional evidence
Abbreviations: ECBS, Endocannabinoids; AEA, An amide hydrolase; CB1, Cannabinoid type 1 receptor; CB2 TRPV1, Transient potential vanilloid type 1 receptor; CBD, tex; MPFC, Medial prefrontal córtex; PL, Prelimbic; HI Hippocampus; PAG, Periaqueductal gray matter; THC, Δ9 Elevated plusmaze; VCT, Vogel conflict test; AP, Anteropos ⁎ Corresponding author at: Pharmacology Departme Preto, University o...
متن کاملInteraction Between the Cannabinoid and Vanilloid Systems on Anxiety in Male Rats
Introduction: Previous studies have shown that the cannabinoid system is involved in anxiety.In addition, transient receptor potential vanilloid type-1 (TRPV1) channels are new targets for the development of anxiolytics. The present study investigated the possible interaction between the cannabinoid and vanilloid systems on anxiety-like behavior in rats. Methods: Four different groups of male ...
متن کاملMorphine-induced analgesic tolerance is associated with alteration of protein kinase Cγ and transient receptor potential vanilloid type 1 genes expression in rat lumbosacral cord and midbrain
Introduction: Transient receptor potential vanilloid type 1 (TRPV1) and protein kinase Cγ (PKCγ) are involved in sensitization/desensitization to noxious stimuli. We aimed to examine the gene expression levels of TRPV1 and PKCγ in rat lumbosacral cord and midbrain on days 1, 4 and 8 of induction of morphine analgesic tolerance. Methods: Two groups of male Wistar rats received ...
متن کاملElevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors.
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 o...
متن کامل