Investigation of the Interaction Between Cannabinoid and Opioid Systems in Chronic Pain Modulation: Involvement of HO-1/CO pathway

• Grant number: 21/12712-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2022
• End date: April 30, 2025
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Christie Ramos Andrade Leite Panissi
• Grantee: Vítor Pansarim
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Pain sensitivity involves the detection of harmful stimuli and activation of central nervous system circuits, being modulated through descending pathways. Pain modulation would involve the integration of endogenous systems activity, such as opioids and cannabinoids. In addition, the carbon monoxide pathway (HO-1/CO) is also involved in pain modulation, and its induction is capable of producing analgesia in rodent chronic pain models. Thus, this project aims to investigate the effects of the interaction between endogenous cannabinoid and opioid systems and their interface with the HO-1/CO pathway in modulating pain sensitivity. For this, male C57BL/6 mice will be submitted to a condition of chronic inflammatory pain, induced by complete Freund's adjuvant (CFA) administration. On the 10th day after the inflammatory pain induction, the animals will undergo a pharmacological treatment with a FAAH inhibitor (PF-3845), enzyme responsible for the degradation of endocannabinoids, or an HO-1 inducer (CoPP). They will then undergo a second treatment with a selective MOR antagonist (CTAP), a selective DOR antagonist (Naltrindole) or an HO-1 inhibitor (SnPP). Pain sensitivity assessment tests will be performed on day 0 (baseline), day 1, day 3, day 7, day 10 pre-treatments and day 10 post-treatments. Western blot analysis will be conducted to investigate the protein expression of opioid receptors, cannabinoid receptors and HO-1 in the periaqueductal gray matter, amygdala and hippocampus (regions related to pain modulation). ANOVAs will be conducted to analyze the effects of the interaction between the chronic pain condition and pharmacological treatments on pain sensitivity and expression of proteins involved in pain modulation.