Research reportInvolvement of oxytocin in spinal antinociception in rats with inflammation
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and that mu- and kappa-opioid receptors, but not delta-opioid receptor, were involved in the effects in normal rats (unpublished data).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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