Role of NMDA receptors blockade in the thalamic paraventricular nucleus in morphine dependent rat model of formalin-induced pain

Evidence shows that the N-methyl-d-aspartate (NMDA) antagonist MK801 reduces the development of morphine (Mor) tolerance. The paraventricular nucleus of the thalamus (PVT) comprises the highest levels of μ-opioid receptors in the thalamus and is involved in pain modulation. The present study examined whether blocking NMDA receptors by administration of MK801 in the PVT nucleus could affect the nociceptive behavioral manifestations caused by the formalin in Mor-dependent rats. Male Wistar rats weighing 250–300 g were dependent on Mor by subcutaneously (s.c.) injection (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. Animals were randomized into four experimental groups in which the NMDA receptor antagonist, MK801 (20 mM in 0.1 ml), or its vehicle were injected into the PVT nucleus for 7 days before each Mor injection. On day 8, the formalin test was carried out. Results showed that repetitive Mor administration prompted antinociception in interphase and phase II of formalin test. Also, inhibition of NMDA receptors decreased formalin-induced nociceptive behaviors in all phases of the test in Mor-dependent rats. Our findings suggested that continuous co-administration of MK801 into PVT with Mor could enhance the antinociceptive effect of Mor and reduce the nociceptive behaviors prompted by formalin in Mor-dependent rats.