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Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on morphine tolerance in rats

Jiang Jianping, Chen Yajuan, Hong Yanguo

Department of Anatomy and Physiology, College of Life Sciences, Fujian Normal University, Key Laboratory of Developmental and Neurological Biology of Fufian Province.Fuzhou 350007,Fujian

Abstract

Bovine adrenal medulla 22 （BAM22）, an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor （SNSR）. The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal （i.t.） administration of morphine for 7 d produced-morphine tolerance in rats. Then the rats were divided into three groups in which morphine, saline or BAM22 were administered i.t., respectively, on day 8, and morphine was given to all of the animals on day 9. It was found that morphine administered on day 9 resumed antinociceptive effects in BAM22 group, but not in saline or morphine group. The potency of morphine in BAM22 group was 48.5% of the maximal possible effect （MPE） detected by paw withdrawal test and the antinociception persisted for approximately 1 h. Following the similar treatment, morphine administered on day 9 reduced nocifensive behaviors by 3.2 rain and 24 rain in BAM22 group in the first and second phases, in the formalin test, respectively. The decreases were 45% and 82% of the corresponding values observed in saline group. Furthermore, following the treatment with BAM22 （10 nmol） on day 8 in morphine-tolerance rats, morphine administered on day 9 decreased the expressions of the heat-evoked c-Fos-like immunoreactivity （FLI） protein by approximately 80% in laminae Ⅰ-Ⅱ, Ⅲ-Ⅳ and Ⅴ-Ⅵ in the spinal cord at L4-L5 compared with that in saline or morphine group. The present study provided evidence at behavioral and cellular levels showing that BAM22 resumed antinociception of morphine. The results that the reversal effect of BAM22 on morphine tolerance was more efficient in persistent pain model than in acute pain may indicate that BAM22 differentially modulates morphine tolerance. The present study suggests that SNSR is involved in the modulation of morphine tolerance.

Key words: bovine adrenal medulla 22;Morphine tolerance;nociception;Spinal dorsal horn;c-Fos protein

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Citing This Article：

Jiang Jianping, Chen Yajuan, Hong Yanguo. Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on morphine tolerance in rats. Acta Physiol Sin 2006; 58 (6): (in Chinese with English abstract).