A Synergistic Analgesic Effect of Morphine in Combination With the Cb1 Receptor Agonist, Acpa, in Normal, Hypothyroid, and Hyperthyroid Male Rats Publisher Pubmed



Zarrindast MR^{1, 2} ; Khakpai F³
Source: Acta Neurobiologiae Experimentalis Published:2023

Abstract

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. © 2023, Nencki Institute of Experimental Biology. All rights reserved.