Abstract
Aim:
To investigate the relationship between spinal cord norepinephrine, α1 and α2 adrenergic receptors and antinociception of propofol in mice.
Methods:
Kunming mice were used. Antinociceptive tests were investigated with the tail-immersion test and the acetic acid-induced writhing test. The effects of subcutaneous (sc), intrathecal (ith) and intracerebroventricular (icv) injection propofol on pain threshold were observed. The influences of pretreatment with ith 6-hydroxydopamine, α1R antagonist prazosin, or α2R antagonist yohimbine on the antinociception of propofol were studied.
Results:
Significant antinociception was produced by propofol (25, 50 mg/kg, sc) and propofol (20, 40 μg, ith) in tail-immersion test and acetic the acid-induced writhing test (P<0.05 or P < 0.01). Icv propofol (10, 20, and 40 μg) did not produce any effect on pain threshold in mice (P > 0.05). The 6-hydroxydopamine (5 and 10 μg), prazosin (5 and 10 μg), or yohimbine (5 and 10 μg) ith alone did not affect basal tai-flick latency (TFL) in conscious mice, but significantly reduced the TFL as measured by tail-immersion test in propofol (50 mg/kg, sc)-treated mice, compared with basal TFL and vehicle groups (P < 0.05 or P < 0.01).
Conclusion:
The spinal cord is a target of propofol antinociception. In mice propofol antinociception is partly mediated by spinal norepinephrine, α1R and α2R.
Similar content being viewed by others
Article PDF
References
Nadeson R, Goodchid CS . Antinociceptive properties of propofol: involvement of spinal cord gamma-aminobutyric acid (A) receptors. J Pharmacol Exp Ther 1997; 282: 1181–6.
Xu AJ, Duan SM, Zeng YM . Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on antinociception of propofol. Acta Pharmacol Sin 2004; 25: 9–14.
Antognini JF, Wang XW, Piercy M, Carstens E . Propofol directly depresses lumbar dorsal horn neuronal responses to noxious stimulation in goats. Can J Anaesth 2000; 47: 273–9.
Anwar MM, Abdel-Rahman MS . Effect of propofol on perception of pain in mice: mechanisms of action. Comp Biochem Physiol A Mol Integr Physiol 1998; 120: 249–53.
Fang F, Proudfit HK . Antinociception produced by microinjection of morphine in the rat periaqueductal gray is enhanced in the foot, but not the tail, by intrathecal injection of alpha1-adrenoceptor antagonists. Brain Res 1998; 790: 14–24.
Feng CY, McAdoo DJ, Willis WD . Periaqueductal gray stimulation induced inhibition of nociceptive dorsal horn neurons in rats is associated with the release of norepinephrine, serotonin, and amino acids. J Pharmacol Exp Ther 1999; 289: 868–76.
Pan YZ, Li DP, Pan HL . Inhibition of glutamatergic synaptic input to spinal Lamina IIo neurons by presynaptic α2-adrenergic receptors. J Neurophysiol 2002; 87: 1938–47.
Baba H, Shimoji K, Yoshimura M . Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinergic neurons. Anesthesiology 2000; 92: 473–84.
Baba H, Goldstein PA, Okamoto M, Kohno T, Ataka T, Yoshimura M, et al. Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spina 1 cord (part 2): effects on somatodendritic sites of GABAergic neurons. Anesthesiology 2000; 92: 485–92.
Zhang CY, Zhu TJ, Hu GX, Chen XY, Liu DX, Chen ZK . Effect of sodium dimercaptopropanesulfonate on antagonism of tetramethylenedisulphotetramine to GABA receptor. Acta Pharmacol Sin 2001; 22: 435–9.
Xu, SY, Biain, RL, Chen, X . Methodology of pharmacological experiments. 3rd ed. Beijing: People's Medical Publishing House; 2002. p 882–7.
Hung KC, Wu HE, Mizoguchi H, Leitermann R, Tseng LF . Intrathecal treatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine blocks the antinociception induced by endomorphin-1 a nd endomorphin-2 given intracerebroventricularly in the mouse. J Pharmacol Sci 2003; 93: 299–306.
Kerz T, Hennes HJ, Feve A, Decq P, Filipetti P, Duvaldestin P . Effects of propofol on H-reflex in humans. Anesthesiology 2001; 94: 32–7.
Loomis CW, Arunachalam KD . Intrathecal St-587: effects on nociceptive reflexes and blood pressure in the rat. J Pharmacol Exp Ther 1992; 263: 428–35.
Howe JR, Wang JY, Yaksh TL . Selective antagonism of the antinociceptive effect of intrathecally applied alpha adrenergic agonists by intrathecal prazosin and intrathecal yohimbine. J Pharmacol Exp Ther 1983; 224: 552–8.
Aran S, Proudfit HK . Antinociceptive interactions between intrathecally administered alpha noradrenergic agonists and 5′-N-ethylcarboxamide adenosine. Brain Res 1990; 519: 287–93.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ge, Zj., Zeng, Ym. & Tan, Yf. Effects of intrathecal 6-hydroxydopamine, α1 and α2 adrenergic receptor antagonists on antinociception of propofol in mice. Acta Pharmacol Sin 26, 186–191 (2005). https://doi.org/10.1111/j.1745-7254.2005.00033.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00033.x
Keywords
This article is cited by
-
Postsynaptic α-2 Adrenergic Receptors are Critical for the Antidepressant-Like Effects of Desipramine on Behavior
Neuropsychopharmacology (2009)