Elsevier

Brain Research

Volume 983, Issues 1–2, 5 September 2003, Pages 13-22
Brain Research

Research report
Involvement of oxytocin in spinal antinociception in rats with inflammation

https://doi.org/10.1016/S0006-8993(03)03019-1Get rights and content

Abstract

The present study was conducted on rats with inflammation induced by subcutaneous injection of carrageenan into the left hindpaw. Intrathecal administration of oxytocin produced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. The antinociceptive effect of oxytocin was blocked by intrathecal administration of atosiban, a selective oxytocin antagonist, indicating that oxytocin receptor mediates oxytocin-induced antinociception in the spinal cord. The oxytocin-induced antinociceptive effect was attenuated by intrathecal administration of the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Furthermore, the antinociceptive effect of oxytocin was attenuated by intrathecal injections of the mu-receptor antagonist β-funaltrexamine and the kappa-receptor antagonist nor-binaltorphimine, but not by the delta-receptor antagonist naltrindole, illustrating that mu- and kappa-receptors, but not delta-receptor, are involved in oxytocin-induced antinociception in the spinal cord of rats with inflammation. Moreover, intrathecal administration of atosiban alone induced a hyperalgesia in rats with inflammation, indicating that endogenous oxytocin is involved in the transmission and regulation of nociceptive information in the spinal cord of rats with inflammation. The present study showed that both exogenous and endogenous oxytocin displayed antinociception in the spinal cord in rats with inflammation, and mu- and kappa-receptors were involved in oxytocin-induced antinociception.

Introduction

Oxytocin-containing axons from the hypothalamic paraventricular nucleus and supraoptic nucleus project to other regions of the brain [28], [29] as well as the spinal cord [8], [14], [28]. It has been reported that there were distribution of oxytocin binding sites [13], [17], [25], [26], [30] and the distribution of opioid receptors [4], [12] in the spinal cord. It is well-known that the opioid system plays a key role in spinal antinociception [9], [10], [22]. Many studies showed that oxytocin displays antinociceptive effects at different levels in the central nervous system [1], [3], [18], [19], [20], [23], [24], [31]. Recent study in our laboratory demonstrated that oxytocin administered to the periaqueductal grey induced antinociception in normal rats, and opioid receptors were involved in the effect [11]. We also showed that intrathecal injection of oxytocin resulted in dose-dependent antinociceptive effects which were mediated by oxytocin receptor and that mu- and kappa-opioid receptors, but not delta-opioid receptor, were involved in the effects in normal rats (unpublished data).

We have now gained much knowledge about the antinociceptive effects of oxytocin in normal animals. In order to obtain a better understanding of the antinociceptive effects of oxytocin in pathological conditions, the present study was carried out to investigate the antinociceptive effects of oxytocin and the role of the opioid system in oxytocin-induced antinociception in the spinal cord in rats with inflammation.

Section snippets

Animals

Experiments were carried out on freely moving male Wistar rats weighing 250–300 g (Experimental Animal Center of Zhengzhou University, Zhengzhou, China). The rats were housed in cages with free access to food and water. All experiments were conducted according to the guidelines of the Animal Ethical Committee of Karolinska Institutet. Every effort was made to minimize animal suffering and the number of animals used.

Inflammation model

Inflammation was induced by subcutaneous injection of 0.1 ml of 2% carrageenan

Effects of intrathecal administration of oxytocin on HWLs to noxious thermal and mechanical stimulation in rats with inflammation

Rats with inflammation received an intrathecal injection of 0.04 (n=8), 0.1 (n=8) or 0.25 nmol of oxytocin (n=8), or 10 μl of 0.9% saline as a control (n=8). As shown in Fig. 1 and Table 1, the HWLs to thermal and mechanical stimulation increased significantly after intrathecal injection of 0.25 or 0.1 nmol of oxytocin, but not 0.04 nmol of oxytocin, compared with the control group. The antinociceptive effect of oxytocin reached a peak at 5 min after intrathecal injection, and then recovered to

Discussion

The animal model with inflammation may provide more knowledge about the modulation of pain in pathological conditions than that in normal conditions. The inflammation model induced by carrageenan is often used in pain study and some interesting results were obtained in our laboratory using this model [16], [32], [37], [38]. Many reports showed an analgesic effect of oxytocin in normal rats [1], [3], [18], [20], [23], [31]. Few reports were conducted on the direct effect of oxytocin in the

Acknowledgements

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

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