Microinjection of morphine into the nucleus accumbens and CA1 modulates pain-related behaviors in an animal model of inflammatory pain in male rats

Studies showed that the nucleus accumbens (NAc) and the CA1 of hippocampus involved in multiple functions. Opioid receptors play a critical role in antinociceptive mechanisms. This study explored the involvement of the opioidergic system in the CA1 and NAc regions in modulating the formalin-induced inflammatory nociceptive responses. One hundred and forty-six adult male Wistar rats were unilaterally implanted by separate cannula into the NAc or CA1. The formalin test was employed to evaluate the effect of the microinjections of morphine in NAc or CA1 on inflammatory pain thresholds in 5-min blocks for 60 min. At the first experiment, animals received microinjections of various doses of morphine (2.5, 5, 10, and 25 mmol/0.5 μl) to evaluate its effects as a μ-opioid receptor agonist in the NAc or CA1. At the next experiment, different doses of naloxone were separately administered into the NAc (0.5, 1.5, 5, and 15 mmol/0.5 μl saline) or CA1 (1.5, 5, 15, and 45 mmol/0.5 μl saline) as a nonselective μ-opioid receptor antagonist, before an effective dose of morphine in the NAc (10 mmol/0.5 μl) and CA1 (25 mmol/0.5 μl). The results revealed that intra-NAc and CA1 injections of morphine cause antinociceptive responses in early and late phases of the formalin test. In addition, naloxone injection, administered before the effective dose of morphine, reduced its analgesic effects in both the NAc and CA1. These findings showed that opioidergic neurons exert antinociceptive effects through modulation of the μ-opioid receptor in the NAc and CA1 regions of the brain.