Efeito da cronificação da dor e da dor crônica em um mecanismo de modulação endógena de dor em ratos

Author(s)

Josiane Miranda

• Document type: Master's Dissertation
• Press: Piracicaba, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2014-02-25

Examining board members

Cláudia Herrera Tambeli; Jozi Godoy Figueiredo; Dionéia Araldi

• Advisor: Cláudia Herrera Tambeli

Abstract

In this study, we tested the hypothesis that the transition from acute to persistent hyperalgesia and persistent hyperalgesia reduces the activity and induces plastic changes in an endogenous analgesia circuit, the ascending nociceptive control (ANC). An important mechanism mediating this form of endogenous analgesia, referred as capsaicin-induced analgesia, is its dependence on nucleus accumbens µ-opioid receptor mechanisms. Therefore, we also investigated whether the transition from acute to persistent mechanical hyperalgesia and persistent mechanical hyperalgesia alters the requirement for nucleus accumbens µ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily intraplantar PGE2 injection into the rat's hind paw for 14 days, referred as the induction period of persistent hyperalgesia, induces a long lasting state of nociceptior sensitization referred as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical mild stimulation of the hind paw. Western blot analysis were used to evaluate the expression of µ-opioid receptors in nucleus accumbens. We found a significant reduction in the duration of capsaicin-induced analgesia at day 7 and 14th of the induction period and at days 1, 7, 14 and 21th of the maintenance period of persistent mechanical hyperalgesia. Intra-accumbens administration of the µ-receptor selective antagonist Cys2,Tyr3,Orn5,Pen7amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. However, no significant changes occurred in the expression of µ-opioid receptors. Taken together, these findings indicate that the transition from acute to persistent hyperalgesia and persistent hyperalgesia reduces the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens µ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain (AU)

• FAPESP's process: 09/12001-6 - The role of ascending nociceptive control in persistent hyperalgesia in rats
• Grantee: Josiane Miranda
• Support Opportunities: Scholarships in Brazil - Master