Effect of persistent hyperalgesia on the defensive behavior of rats and in the ability of an endogenous analgesia circuit to modulate it

Author(s)

Simone Monaliza Silva Lamana

• Document type: Master's Dissertation
• Press: Piracicaba, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2013-02-05

Examining board members

Cláudia Herrera Tambeli; Christie Ramos de Andrade Leite Panissi; Eduardo Dias de Andrade

• Advisor: Cláudia Herrera Tambeli

Abstract

The dorsal immobility response is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition induced by some forms of physical restraint. When the animal is in a dangerous situation it needs to engage in defensive responses without interference from the motivational conflicts to engage in recuperative behaviors. However, it is unclear whether the persistent inflammatory hyperalgesia (PIH) could affect the defensive behavior of dorsal immobility (DBDI) in rats. Recently, our research group has demonstrated that acute peripheral pain through activation of endogenous neural circuitry of pain modulation known for ascending nociceptive control (ANC), enhances the duration of the DBDI in rats through a mechanism opioid-dependent on the nucleus accumbens (NAc). Moreover, the PIH could be the conflict source. Based on this, the proposal of the present study was to investigate whether PIH affects the DBDI and the modulation that intense acute peripheral pain, via ANC activation, exerts on this defensive behavior. The PIH was induced by using an experimental model in which hyperalgesia lasting for about 30 days after the daily administration of prostaglandin E2 (PGE2) for 14 days in the subcutaneous tissue of the rats' hind paw. The DBDI was induced by suspending the adult rat the skin of the nape. Investigating whether PIH affects the DBDI, immobility dorsal behavior was evaluated on days 1, 7, and 14, prostaglandin E2 (induction period of PIH) or its vehicle in the subcutaneous tissue of the rats' hind paw and on days 1, 7, 14, and 21 after cessation of treatment with prostaglandin E2 (maintenance period of PIH). Investigating whether PIH affects modulation of the intense peripheral acute pain, via activation of ANC, carries on the DBDI, capsaicin was administered subcutaneously in the fore paw to induce peripheral nociceptive stimulation and activate the ANC on days 1, 7, and 14 prostaglandin E2 and on days 1, 7, 14, and 21 after discontinuation of PGE2. Ten minutes before administration of the capsaicin ?-opioid receptor antagonist, CTOP, or its vehicle was administered in the NAc and immediately after administration of capsaicin, the dorsal immobility response was evaluated, and the locomotor activity of the animals in the equipment Rota-rod. The results demonstrate for the first time that PIH decreases the duration of DBDI in rats in both induction and maintenance periods of PIH. They also show that intense peripheral nociceptive stimulation via activation ANC increases the duration of dorsal immobility response in rats during periods of induction and maintenance of PIH, and that this effect is prevented by the prior intra-accumbal administration of the ?-opioid receptor antagonist, CTOP (Cys2, Tyr3, Orn5, Pen7amide). These results suggest that PIH affects the DBDI, by reducing its duration, but does not affect the ability of endogenous pain modulation mechanisms, such as the ANC, to facilitate defensive behaviors (AU)

• FAPESP's process: 09/12270-7 - Effect of persistent hyperalgesia on the defensive behavior of rats: Participation of the Ascending Nociceptive Control.
• Grantee: Simone Monaliza Silva Lamana
• Support Opportunities: Scholarships in Brazil - Master