Wang H, Sagen J
Department of Anatomy and Cell Biology, University of Illinois at Chicago 60612.
Neuropharmacology. 1994 May;33(5):681-92. doi: 10.1016/0028-3908(94)90174-0.
Adrenal medullary transplants in the spinal subarachnoid space may be a means of achieving sustained local delivery of pain-reducing neuroactive substances on a continually renewable basis. However, a potential limitation of this approach is tolerance development to agents released from the transplanted cells. In particular, since adrenal medullary chromaffin cells release opioid peptides, reduced antinociceptive efficacy of opioids is possible. To determine this, alterations in the dose-effectiveness of morphine were assessed in animals with adrenal medullary transplants. Results indicated that, not only was there no apparent tolerance, but that adrenal medullary transplants could potentiate the analgesic efficacy of morphine. An additional goal of these studies was to determine whether chronic or intermittent nicotine could produce increased antinociception, since stimulation of cell surface nicotinic receptors increases release of neuroactive substances from chromaffin cells. This was assessed using subcutaneously implanted nicotine pellets or repeated systemic administration of nicotine. Findings indicated that exposure to nicotine results in an acute tolerance, or tachyphylaxis, to nicotine which is rapidly reversed following cessation of nicotinic stimulation. Together, these results suggest that adrenal medullary transplants may provide a constant source of opioid peptides, augmentable by intermittent nicotinic stimulation, without the development of appreciable tolerance to these pain-reducing neuroactive substances.
将肾上腺髓质移植到脊髓蛛网膜下腔可能是一种在持续可再生的基础上实现疼痛减轻神经活性物质持续局部递送的方法。然而，这种方法的一个潜在限制是对移植细胞释放的物质产生耐受性。特别是，由于肾上腺髓质嗜铬细胞释放阿片肽，阿片类药物的抗伤害感受效力可能降低。为了确定这一点，在进行肾上腺髓质移植的动物中评估了吗啡剂量效应的变化。结果表明，不仅没有明显的耐受性，而且肾上腺髓质移植可以增强吗啡的镇痛效力。这些研究的另一个目标是确定慢性或间歇性尼古丁是否会产生增强的抗伤害感受作用，因为刺激细胞表面烟碱受体可增加嗜铬细胞释放神经活性物质。这通过皮下植入尼古丁丸剂或重复全身给予尼古丁来评估。研究结果表明，接触尼古丁会导致对尼古丁产生急性耐受性或快速耐受性，在烟碱刺激停止后这种耐受性会迅速逆转。总之，这些结果表明，肾上腺髓质移植可能提供阿片肽的恒定来源，通过间歇性烟碱刺激可增强其作用，而不会对这些减轻疼痛的神经活性物质产生明显的耐受性。
