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Autoradiographic study of G-protein coupling to cannabinoid CB1-receptors in the brain of rats with peripheral mononeuropathy

AuthorsDíaz, Álvaro CSIC ORCID; Rojo, María Luisa CSIC; Rodríguez-Gaztelumendi, A. CSIC ORCID; Pazos, Ángel CSIC ORCID
Issue Date2008
PublisherJohn Wiley & Sons
CitationFundamental and Clinical Pharmacology 22(s2): 70 (2008)
AbstractAlterations in signal transduction of different types of neurotransmitter receptors involved in pain transmission and processing may occur during neuropathic pain. Several basic lines and clinical evidences have demonstrated the role of cannabinoid neurotransmission in the control and treatment of pain. In this autoradiographic study, we have evaluated the coupling efficacy of G-proteins to brain CB1-receptors in a model of neuropathic pain. Peripheral mononeuropathy in male Sprague-Dawley rats, 2 months old (neuropathic animals, n = 8; sham-operated, n = 7), was performed following the >spared nerve injury> model (Decosterd and Woolf, 2000). Abnormal pain behaviour -decreased hind-paw withdrawal thresholds to tactile and noxious mechanical stimulation- was at a stable maximum following 14 days of surgery. The functionality of cannabionid CB1 receptors was assessed in brain and spinal cord sections by measuring the stimulation of [35S]GTPcS binding induced by the cannabinoid agonist WIN55.212 (10 lM), The specificity of the agonist-induced response was confirmed using the selective CB1 antagonist SR141716A (10 lM). In rats with mononeuropathy, agonist-induced specific stimulation of [35S]GTPcS binding was significantly enhanced in cingulate cortex, septal nuclei and susbtantia nigra (+16%, +31% and +43% over basal binding, respectively) whereas it was reduced in other areas such as hippocampal dentate gyrus, entorhinal cortex and raphe magnus nuclei ()18%, )15%, )26% above basal binding, respectively). These results demonstrate a differential regulation, regionally-dependent, of the functionality of brain CB1 receptors during neuropathic pain. These data may help to understand the role of cannabinoid neurotransmission in the pathogenesis of neuropathic pain as well as to develop potential therapeutical targets.
DescriptionTrabajo presentado al EPHAR 2008 Congress celebrado en Manchester.
Identifiersdoi: 10.1111/j.1472-8206.2008.00596.x
issn: 0767-3981
e-issn: 1472-8206
Appears in Collections:(IBBTEC) Artículos
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