An Experimental Study on Spinal Cord µ-Opioid and α2-Adrenergic Receptors mRNA Expression Following Stress-Induced Hyperalgesia in Male Rats

Asef Hormozi, Asadollah Zarifkar, Bahar Rostami, Fakhraddin Naghibalhossaini


Background: Intense stress can change pain perception and induce hyperalgesia; a phenomenon called stress-induced hyperalgesia (SIH). However, the neurobiological mechanism of this effect remains unclear. The present study aimed to investigate the effect of the spinal cord µ-opioid receptors (MOR) and α2-adrenergic receptors (α2-AR) on pain sensation in rats with SIH.
Methods: Eighteen Sprague-Dawley male rats, weighing 200-250 g, were randomly divided into two groups (n=9 per group), namely the control and stress group. The stress group was evoked by random 1-hour daily foot-shock stress (0.8 mA for 10 seconds, 1 minute apart) for 3 weeks using a communication box. The tail-flick and formalin tests were performed in both groups on day 22. The real-time RT-PCR technique was used to observe MOR and α2-AR mRNA levels at the L4-L5 lumbar spinal cord. Statistical analysis was performed using the GraphPad Prism 5 software (San Diego, CA, USA). Student’s t test was applied for comparisons between the groups. P<0.05 was considered statistically significant.
Results: There was a significant (P=0.0014) decrease in tail-flick latency in the stress group compared to the control group. Nociceptive behavioral responses to formalin-induced pain in the stress group were significantly increased in the acute (P=0.007) and chronic (P=0.001) phases of the formalin test compared to the control group. A significant reduction was also observed in MOR mRNA level of the stress group compared to the control group (P=0.003). There was no significant difference in α2-AR mRNA level between the stress and control group. Conclusion: The results indicate that chronic stress can affect nociception and lead to hyperalgesia. The data suggest that decreased expression of spinal cord MOR causes hyperalgesia.


Stress; Hyperalgesia; Spinal cord; Receptors, opioid, mu; Adrenergic alpha-2 receptor antagonists

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pISSN: 0253-0716         eISSN: 1735-3688