Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and expression of tolerance to morphine in rats

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• 作者：Qiaoyan Cai ; Jianping Jiang ; Tingjun Chen ; Yanguo Hong
• 关键词：Morphine tolerance ; Bovine adrenal medulla 8-22 (BAM8-22) ; Sensory neuron-specific receptor (SNSR) ; Antinociception ; Spinal cord
• 刊名：Behavioural Brain Research
• 出版年：2007
• 出版时间：12 March 2007
• 年：2007
• 卷：178
• 期：1
• 页码：154-159
• 全文大小：217 K

文摘

We observed that intrathecal (i.t.) bovine adrenal medulla 22, an endogenous opioid peptide, partially reverses morphine tolerance. However, its mechanism remains unclear. The present study determined the effects of BAM8-22, a derivative of BAM22 and selective sensory neuron-specific receptor (SNSR) agonist, on the development and maintenance of tolerance to spinal morphine. Intrathecal administration of BAM8-22 at various doses (0.1, 1 and 10 nmol) did not alter withdraw latencies assessed in both paw withdraw and tail flick tests. Co-administration of BAM8-22 (0.1 nmol) every other day, but not daily, with morphine remarkably attenuated the development of morphine tolerance. Pretreatment and co-treatment with BAM8-22 (0.1 nmol) significantly reversed established morphine tolerance. Furthermore, intermittent administration of BAM8-22 with morphine consistently resumed morphine-induced antinociception. However, i.t. BAM8-22 did not alter morphine-induced hyperalgesia. These results suggested that SNSR may be able to modulate the sensitivity of opioid receptor serving as a most probable underlying mechanism for the effects of BAM8-22 on morphine tolerance. This study also demonstrated that intermittent combination of SNSR agonist BAM8-22 with morphine might be better regimen for long-term use of opioids to treat chronic pain.