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Information Seminar Paper

Title

INVOLVEMENT OF CANNABINOID TYPE-1 RECEPTORS IN OREXIN-A INDUCED ANALGESIA IN RAT LOCUS COERULEUS

Writers

ESSLAMZADEH GH.

Pages

 Start Page | End Page

Abstract

 INTRODUCTION: LOCUS COERULEUS (LC) NUCLEUS IS INVOLVED IN NORADRENERGIC DESCENDING PAIN MODULATION. LC RECEIVES DENSE OREXINERGIC PROJECTIONS FROM THE LATERAL HYPOTHALAMUS. OREXIN-A AND -B ARE HYPOTHALAMIC PEPTIDES WHICH MODULATE A VARIETY OF BRAIN FUNCTIONS VIA OREXIN TYPE-1 (OX1) AND OREXIN TYPE-2 (OX2) RECEPTORS. PREVIOUS STUDIES HAVE SHOWN THAT ACTIVATION OF OX1 RECEPTORS, INDUCE END OCANNABINOID PRODUCTION AND ALTER SYNAPTIC NEUROTRANSMISSION THROUGH THE RETROGRADE SIGNALING VIA CANNABINOID TYPE-1 (CB1) RECEPTORS. IN THE PRESENT STUDY THE EFFECT OF INTERACTION BETWEEN OREXIN-A AND END OCANNABINOIDS WAS EXAMINED AT THE LC LEVEL IN A RAT MODEL OF INFLAMMATORY PAIN.METHODS: PAIN WAS INDUCED BY FORMALIN (2%) INJECTION INTO THE HIND PAW.RESULTS: INTRA-LC MICROINJECTION OF OREXIN-A DECREASED THE NOCICEPTION SCORE DURING BOTH PHASES OF FORMALIN TEST. FURTHERMORE, INTRA-LC MICROINJECTION OF EITHER SB-334867 (OX1 RECEPTOR ANTAGONIST) OR AM251 (CB1 RECEPTOR ANTAGONIST) INCREASED FLINCHES AND ALSO THE NOCICEPTION SCORE DURING PHASE 1, 2 AND THE INTER-PHASE OF FORMALIN TEST. ANALGESIC EFFECT OF OREXIN-A WAS DIMINISHED BY PRIOR INTRA-LC MICROINJECTION OF EITHER SB-334867 OR AM251.CONCLUSION: THIS DATA SHOW THAT, ACTIVATION OF OX1 RECEPTORS IN THE LC CAN INDUCE ANALGESIA AND ALSO THE BLOCKADE OF OX1 OR CB1 RECEPTORS IS ASSOCIATED WITH HYPERALGESIA DURING FORMALIN TEST. OUR FINDINGS ALSO SUGGEST THAT CB1 RECEPTORS MAY MODULATE THE ANALGESIC EFFECT OF OREXIN-A. THESE RESULTS OUTLINE A NEW MECHANISM BY WHICH OREXIN-A MODULATES THE NOCICEPTIVE PROCESSING IN THE LC NUCLEUS.

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