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奥曲肽与吗啡在大鼠急性炎性疼痛模型中的镇痛效果比较

Comparison of Antinociceptive Effect of Octreotide With Morphine in a Rat Model of Acute Inflammatory Pain.

作者信息

Singh Perminder, Ray Subrata Basu

机构信息

Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Ann Neurosci. 2021 Jan;28(1-2):13-20. doi: 10.1177/09727531211013004. Epub 2021 Jun 7.

Abstract

BACKGROUND

Opioids such as morphine are used for treating moderate to severe pain. However, they also produce adverse effects such as nausea, constipation, addiction, and respiratory depression. Thus, other suitable analgesics need to be identified. Somatostatin is an inhibitory neuropeptide that modulates the transmission of pain. However, the half-life of somatostatin is short. In the present study, the antinociceptive effect of octreotide (a stable long-acting analog of somatostatin) was evaluated in rats with acute inflammatory pain.

METHODS

Sprague Dawley rats ( = 42) were divided into control ( = 6) and carrageenan injected groups ( = 36). The carrageena group was divided into three equal subgroups and treated with saline, morphine (10 mg/kg), and octreotide (3 µg). Rats belonging to each subgroup ( = 12) were again randomly divided into two equal sets. They were subjected to (a) behavioral evaluation of pain (allodynia) and estimation of paw edema, followed by immunohistochemical analysis of the expression of somatostatin type 2 receptor (sst2r) in the spinal cord and (b) estimation of open-field activity. Allodynia and paw edema were measured by von Frey filaments and plethysmometer, respectively, at 3 and 4 h after carrageenan injection. Expression of sst2r was examined after 24 hours, whereas open-field activity was evaluated after 3 hours.

RESULTS

In comparison to the saline-treated group, allodynia was partially attenuated by octreotide, though this was almost completely reversed by morphine. Paw edema was unaffected by octreotide, though it was marginally increased by morphine. This was not related to increased activity of rats, following relief from pain. Immunohistochemistry revealed a significant increase in the expression of sst2r in saline-treated rats, but a decrease in other groups.

CONCLUSION

Octreotide has an antinociceptive effect, which was less than morphine. Increased edema following morphine could result from venodilation. Variations in the sst2r expression suggest its involvement in pain modulation at the spinal level. This information may have clinical relevance.

摘要

背景

吗啡等阿片类药物用于治疗中度至重度疼痛。然而,它们也会产生诸如恶心、便秘、成瘾和呼吸抑制等不良反应。因此,需要确定其他合适的镇痛药。生长抑素是一种调节疼痛传递的抑制性神经肽。然而,生长抑素的半衰期很短。在本研究中,评估了奥曲肽(一种稳定的长效生长抑素类似物)对急性炎性疼痛大鼠的镇痛作用。

方法

将42只斯普拉格-道利大鼠分为对照组(6只)和角叉菜胶注射组(36只)。角叉菜胶组再分为三个相等的亚组,分别用生理盐水、吗啡(10mg/kg)和奥曲肽(3μg)治疗。每个亚组的12只大鼠再次随机分为两组。对它们进行(a)疼痛行为评估(痛觉过敏)和爪部水肿评估,随后对脊髓中2型生长抑素受体(sst2r)的表达进行免疫组织化学分析,以及(b)旷场活动评估。分别在注射角叉菜胶后3小时和4小时,用von Frey细丝和体积描记器测量痛觉过敏和爪部水肿。24小时后检查sst2r的表达,3小时后评估旷场活动。

结果

与生理盐水治疗组相比,奥曲肽可部分减轻痛觉过敏,不过吗啡几乎可完全逆转这种情况。奥曲肽对爪部水肿无影响,而吗啡使其略有增加。这与大鼠疼痛缓解后活动增加无关。免疫组织化学显示,生理盐水治疗组大鼠的sst2r表达显著增加,而其他组则减少。

结论

奥曲肽具有镇痛作用,但其作用小于吗啡。吗啡导致的水肿增加可能是由于静脉扩张。sst2r表达的变化表明其参与脊髓水平的疼痛调节。这一信息可能具有临床相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e49/8558988/587f57796069/10.1177_09727531211013004-fig1.jpg

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