A synergistic analgesic effect of morphine in combination with the CB1 receptor agonist, ACPA, in normal, hypothyroid, and hyperthyroid male rats.

Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphine and cannabis in rats has been shown to decrease thyroid weight and thyroid‑stimulating hormone (TSH) levels. We hypothesized that the third ventricle, due to its adjacency to the hypothalamus, is involved in the modulation of hypothalamic‑pituitary‑thyroid axis activity and descending pain pathways. The present study examined the effect of intra‑third ventricle administration of morphine and cannabis agents on the modulation of pain behavior in normal, hypothyroid (increased serum TSH), and hyperthyroid (decreased serum TSH) rats using the tail‑flick test. The results indicated that intra‑third ventricle injection of AM251 (CB1 receptor antagonist) caused hyperalgesia, while intra‑third ventricle administration of ACPA (CB1 receptor agonist) and morphine produced analgesia in normal, hypothyroid, and hyperthyroid rats. A non‑effective dose of morphine (0.5 μg/rat) did not attenuate hyperalgesia induced by an effective dose of AM251. Co‑injection of ACPA and morphine into the third ventricle induced anti‑nociceptive effect in normal, hypothyroid, and hyperthyroid rats. An isobolographic analysis demonstrated a synergistic effect between ACPA and morphine in the production of the anti‑nociceptive effect. Consequently, the third ventricle may modulate pain behavior induced by cannabinoid and opioid receptors via descending pain pathways in normal, hypothyroid, and hyperthyroid rats.