Involvement of 5-hydroxytryptamine1A receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation

doi:10.1016/S0306-4522(02)00038-6

Neuroscience

Volume 112, Issue 2, 18 June 2002, Pages 399-407

https://doi.org/10.1016/S0306-4522(02)00038-6 Get rights and content

Abstract

Studies have shown that 5-hydroxytryptamine (5-HT) plays an important role in the descending pathway of pain modulation from brainstem to the spinal cord. Using selective 5-HT receptor antagonists, the present study investigated which type of 5-HT receptor(s) in the spinal cord was involved in the morphine-induced anti-nociception in intact rats, in rats with nerve injury and in rats with inflammation. The hindpaw withdrawal latencies decreased significantly after sciatic nerve injury and hindpaw inflammation compared with intact rats. Intrathecal administration of 25 or 10 μg of the selective 5-HT_1A recepter antagonist spiroxatrine, but not 1 μg of spiroxatrine, significantly blocked the increased hindpaw withdrawal latencies to thermal and mechanical stimulation induced by intra-periaqueductal gray injection of 1 μg of morphine in intact rats. Intrathecal injection of the 5-HT₂ receptor antagonist RS 102221 and the 5-HT₃ receptor antagonist MDL 72222 had no significant effects on the increased hindpaw withdrawal latencies to both noxious stimulations induced by intra-periaqueductal gray injection of morphine. Furthermore, intrathecal administration of spiroxatrine, but not RS 102221 nor MDL 72222, significantly attenuated the increased hindpaw withdrawal latencies induced by intra-periaqueductal gray administration of morphine in rats with nerve injury and in rats with inflammation.

The results demonstrate that the 5-HT_1A receptor, not 5-HT₂ nor 5-HT₃ receptor, plays an important role in the descending pathway of anti-nociception from the brainstem to the spinal cord in intact rats, in rats with nerve injury and in rats with inflammation.

Section snippets

Animal preparation

Freely moving male Sprague–Dawley rats weighing 250–300 g (Experimental Animal Center of Peking University, Beijing, China) were used in the present experiments, which were conducted according to the guidelines of the animal ethical committee of the Karolinska Institute. Every effort was made to minimize both the animal suffering and the number of animals used.

Nerve injury model

To produce a nerve injury model (Bennett and Xie, 1988), the rats were anesthetized with intraperitoneal sodium pentobarbital (45 mg/kg)

Influence of nerve injury and inflammation on the basal HWL to thermal and mechanical stimulation

A group with eight rats received left common sciatic nerve injury. Eight days after nerve injury, the HWLs to both stimulation were significantly decreased bilaterally compared with the HWLs before the injury (thermal test: t_left/left=17.78, P<0.001; t_right/right=8.45, P<0.001. Mechanical test: t_left/left=13.09, P<0.001; t_right/right=8.27, P<0.001), as shown in Fig. 1.

Six rats received injection of 0.1 ml of carrageenan into the left plantar hindpaw. The HWLs were assessed before and 3 h after

Discussion

The results of the present study demonstrated that intra-PAG administration of 1 μg of morphine induced significant increases in the HWL to thermal and mechanical stimulation. The anti-nociceptive effects of morphine were dose-dependently attenuated by intrathecal injections of the 5-HT_1A receptor antagonist, but not by the 5-HT₂ nor 5-HT₃ receptor antagonist, suggesting that the 5-HT_1A receptor, not the 5-HT₂ nor 5-HT₃ receptor, is responsible for the anti-nociceptive role in the descending

Conclusion

Sciatic nerve injury and tissue inflammation elicited significant increases in the concentration of 5-HT in dorsal horn of the spinal cord in rats displaying hyperalgesia. Intra-PAG injection of morphine induced pronounced anti-nociception in intact rats, in rats with nerve injury and in rats with inflammation. In all cases, the anti-nociception was blocked by an intrathecal injection of the 5-HT_1A receptor antagonist, spiroxatrine, but not by the 5-HT₂ nor 5-HT₃ receptor antagonist, RS 10222

Acknowledgments

This study was supported by funds from the National Natural Science Foundation of China (NSFC), Foundation of Karolinska Institutet (Sweden).

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Involvement of 5-hydroxytryptamine1A receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation

Abstract

Section snippets

Animal preparation

Nerve injury model

Influence of nerve injury and inflammation on the basal HWL to thermal and mechanical stimulation

Discussion

Conclusion

Acknowledgments

Pain

Pain

Neuropharmacology

Prog. Neurobiol.

Pain

Mol. Brain Res.

Pain

Brain Res.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Brain Res.

Pain

Prog. Neurobiol.

Brain Res.

Pain

Eur. J. Pharmacol.

Prog. Brain Res.

Brain Res.

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Brain Res.

Neuroscience

Brain Res.

Involvement of 5-hydroxytryptamine_1A receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation