Role of the endocannabinoid system in orofacial muscular pain related to Parkinson's Disease

Abstract

In the present century, a large part of the population is affected by multiple orofacial muscular pains, due to stress, problems in the joint, bruxism, muscular overload, referred pain, traumas, among others. A percentage of this affected population is those with Parkinson's disease. Studies show an association between the prevalence of Parkinson's disease and Temporomandibular Dysfunction, with women being the most affected. Thus, the aim of this project is the investigation of the effect of new analgesic therapy with low recurrence of side effects for orofacial muscular pain symptomatology related to Parkinson's disease, and to test the experimental conditions proposed in males and females in order to cover a more representative the effects. Wistar rats (150 g) were initially divided into two groups (Parkinsonian model and Sham group), subdivided into two types of treatment (cannabidiol - CBD and saline) and cannabidiol (10, 30 and 100 mg/kg) will be administered systemically and locally. Stereotaxic surgery will be performed to inject the toxin 6-hydroxydopamine (6-OHDA - parkinsonian) or saline (Sham group) into the medial prosencephalic bundle and a 21-day recovery period will be awaited for initiation of treatments and motor tests . The nociceptive tests will be: mechanical allodynia by von Frey (paw and orofacial), cold allodynia by acetone test, thermal hyperalgesia by the tail and hot plate retest test and chemical hyperalgesia by the orofacial formalin test. Considering that rats may have a nociception alteration according to the stage of the estrous cycle (Proestro, Estro, Metaestrous, Diestro), we defined a stage for the evaluation of the tests, by pilot experiments already performed. After euthanasia, the masseter muscles, trigeminal ganglia and encephalic muscles will be collected and processed for immunohistochemical evaluation with labeling for CB1 and CB2, Fos-B and tyrosine hydroxylase (TH) receptors.