Marinelli Silvia, Vaughan Christopher W, Schnell Stephen A, Wessendorf Martin W, Christie MacDonald J
Department of Pharmacology and The Medical Foundation, The University of Sydney, Sydney, New South Wales 2006 Australia.
J Neurosci. 2002 Dec 15;22(24):10847-55. doi: 10.1523/JNEUROSCI.22-24-10847.2002.
The rostral ventromedial medulla (RVM) forms part of a descending pathway that modulates nociceptive neurotransmission at the level of the spinal cord dorsal horn. However, the involvement of descending RVM systems in opioid analgesia are a matter of some debate. In the present study, patch-clamp recordings of RVM neurons were made from rats that had received retrograde tracer injections into the spinal cord. More than 90% of identified spinally projecting RVM neurons responded to opioid agonists. Of these neurons, 53% responded only to the mu-opioid agonist D-Ala2, N-Me-Phe4, Gly-ol5 enkephalin, 14% responded only to the kappa-opioid agonist U-69593, and another group responded to both mu and kappa opioids (23%). In unidentified RVM neurons, a larger proportion of neurons responded only to mu opioids (75%), with smaller proportions of kappa- (4%) and mu/kappa-opioid (13%) responders. These RVM slices were then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic neurons. Forty-percent of spinally projecting neurons and 11% of unidentified neurons were TPH positive. Of the TPH-positive spinally projecting neurons, there were similar proportions of mu- (33%), kappa- (25%), and mu/kappa-opioid (33%) responders. Most of the TPH-negative spinally projecting neurons were mu-opioid responders (67%). These findings indicate that functional opioid receptor subtypes exist on spinally projecting serotonergic and nonserotonergic RVM neurons. The proportions of mu- and kappa-opioid receptors expressed differ between serotonergic and nonserotonergic neurons and between retrogradely labeled and unlabeled RVM neurons. We conclude that important roles exist for both serotonergic and nonserotonergic RVM neurons in the mediation of opioid effects.
延髓头端腹内侧区（RVM）是下行通路的一部分，该通路在脊髓背角水平调节伤害性神经传递。然而，下行RVM系统在阿片类镇痛中的作用仍存在一些争议。在本研究中，对接受逆行示踪剂注射到脊髓的大鼠的RVM神经元进行了膜片钳记录。超过90%的已鉴定的投射到脊髓的RVM神经元对阿片类激动剂有反应。在这些神经元中，53%仅对μ-阿片类激动剂D-Ala2、N-Me-Phe4、Gly-ol5脑啡肽有反应，14%仅对κ-阿片类激动剂U-69593有反应，另一组对μ和κ阿片类药物都有反应（23%）。在未鉴定的RVM神经元中，更大比例的神经元仅对μ阿片类药物有反应（75%），对κ-（4%）和μ/κ-阿片类药物（13%）有反应的比例较小。然后对这些RVM切片进行色氨酸羟化酶（TPH）免疫染色，TPH是血清素能神经元的标志物。40%的投射到脊髓的神经元和11%的未鉴定神经元TPH呈阳性。在TPH阳性的投射到脊髓的神经元中，对μ-（33%）、κ-（25%）和μ/κ-阿片类药物（33%）有反应的比例相似。大多数TPH阴性的投射到脊髓的神经元是μ-阿片类药物反应者（67%）。这些发现表明，在投射到脊髓的血清素能和非血清素能RVM神经元上存在功能性阿片受体亚型。血清素能和非血清素能神经元之间以及逆行标记和未标记的RVM神经元之间表达的μ和κ阿片受体比例不同。我们得出结论，血清素能和非血清素能RVM神经元在阿片类药物作用的介导中都发挥着重要作用。
