Sherman S E, Luo L, Dostrovsky J O
Department of Physiology, University of Toronto, Ontario, Canada.
J Neurophysiol. 1997 Aug;78(2):628-37. doi: 10.1152/jn.1997.78.2.628.
Experiments in both conscious and anesthetized animals indicate that intrathecal (i.t.) strychnine (STR; glycine receptor antagonist) produces acute, reversible allodynia, as evidenced by inappropriate behavioral and autonomic responses to cutaneous tactile stimuli. Although STR is known to produce disinhibition of afferent input to the spinal cord, changes in spinal reflexes cannot fully explain the complex behaviors observed following i.t. STR. Which supraspinal sites are involved in STR-dependent allodynia and how this abnormal somatosensory message is relayed to these sites remain to be determined. The medial thalamus contains many nociceptive-specific (NS) neurons and is believed to be involved in mediating the affective-motivational aspects of pain. It is thus important to determine whether spinally administered STR elicits changes in the responses of medial thalamic NS neurons. Extracellular single-unit recordings were conducted in urethan-anesthetized rats (290-490 g). A detailed characterization of 20 thalamic NS units (1 per rat; 2 in 1 case) was conducted before and immediately after i.t. STR (40 microg). Initially, all of the units in this study were classified as NS, because they were excited by noxious pinch but not by innocuous tactile stimuli. After i.t. STR, all (formerly NS) units exhibited significant responses to innocuous tactile stimuli (brush and/or air jet) applied to lumbar or sacral dermatomes. This effect of STR on thalamic NS neurons was acute and reversible. The majority of units (11 of 20) also exhibited an increase in spontaneous firing rate. Although the complete pinch receptive field (RF) could not be determined for all units, the available data indicate that the RFs for brush stimulation after i.t. STR were substantially different from the pre-STR pinch RFs for all but three units. The same i.t. STR injection that caused the observed changes in medial thalamus also produced allodynia, in the form of brush-evoked cardiovascular or motor responses, in 18 of the 19 rats. The ability of NS cells in medial thalamus to respond to tactile input after i.t. STR suggests that the STR lowers the threshold of nociceptive neurons that project directly and/or indirectly to medial thalamus. These observations suggest that ascending nociceptive pathways and medial thalamic structures contribute to the expression of STR-dependent allodynia.
在清醒和麻醉动物身上进行的实验表明,鞘内注射士的宁(STR;甘氨酸受体拮抗剂)会产生急性、可逆的痛觉过敏,对皮肤触觉刺激出现不适当的行为和自主反应就证明了这一点。虽然已知STR会导致脊髓传入输入的去抑制,但脊髓反射的变化并不能完全解释鞘内注射STR后观察到的复杂行为。哪些脊髓上部位参与了STR依赖性痛觉过敏,以及这种异常的躯体感觉信息是如何传递到这些部位的,仍有待确定。内侧丘脑包含许多伤害性特异性(NS)神经元,被认为参与介导疼痛的情感动机方面。因此,确定脊髓注射STR是否会引起内侧丘脑NS神经元反应的变化很重要。在乌拉坦麻醉的大鼠(290 - 490克)身上进行了细胞外单单位记录。在鞘内注射STR(40微克)之前和之后立即对20个丘脑NS单位(每只大鼠1个;1例中有2个)进行了详细表征。最初,本研究中的所有单位都被归类为NS,因为它们受到有害捏压刺激的兴奋,但不受无害触觉刺激的兴奋。鞘内注射STR后,所有(以前为NS)单位对应用于腰部或骶部皮节的无害触觉刺激(刷和/或喷气)都表现出明显反应。STR对丘脑NS神经元的这种作用是急性且可逆的。大多数单位(20个中的11个)的自发放电率也有所增加。虽然并非所有单位都能确定完整的捏压感受野(RF),但现有数据表明,除了三个单位外,鞘内注射STR后刷刺激的RF与STR注射前捏压的RF有很大不同。导致内侧丘脑出现观察到的变化的相同鞘内STR注射,在19只大鼠中的18只中还产生了痛觉过敏,表现为刷诱发的心血管或运动反应。内侧丘脑的NS细胞在鞘内注射STR后对触觉输入产生反应的能力表明,STR降低了直接和/或间接投射到内侧丘脑的伤害性神经元的阈值。这些观察结果表明,上行伤害性通路和内侧丘脑结构参与了STR依赖性痛觉过敏的表达。