Carstens E
Section of Neurobiology, Physiology, and Behavior, University of California, Davis 95616, USA.
J Neurophysiol. 1997 May;77(5):2499-514. doi: 10.1152/jn.1997.77.5.2499.
To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-type lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses were recorded to mechanical and noxious thermal stimuli, as well as to microinjection (1 microl) of histamine (0.01-10% = 9 x 10(-1)-9 x 10(-4) M), capsaicin (0.1% = 3.3 x 10(-3) M), or other algesic chemicals into skin within the receptive field via intracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (i.c.) microinjection of histamine with a brief phasic discharge followed by an afterdischarge of variable (s to min) duration. Ten minutes after i.c. microinjection of histamine (but not NaCl), there was a significant increase in the mean area of the low-threshold (but not high-threshold) portion of unit mechanical receptive fields. However, responses to graded pressure stimuli were not significantly affected after histamine. Responses did not exhibit significant tachyphylaxis when histamine microinjections were repeated at 5- or 10-min intervals. Unit responses significantly increased in a dose-related manner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after i.c. microinjection of the H1 antagonist cetirizine, unit responses to i.c. histamine delivered at the same skin site were significantly attenuated. Unit responses to histamine, as well as to noxious thermal stimulation, were significantly reduced after systemic administration of morphine (3.5 mg/kg i.p.) in a naloxone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to i.c. histamine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were markedly suppressed by electrical stimulation in the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested also responded to i.c. microinjection of capsaicin. After the initial microinjection of capsaicin, subsequent responses to histamine and capsaicin microinjections were significantly reduced. Units also responded to i.c. ethanol (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to repeated i.c. ethanol at 80% but not at 8%. The mean response to 80% ethanol was significantly smaller than to 0.1% capsaicin. All units tested also responded to topical application of mustard oil (50%) and i.c. serotonin (30 microg). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.
为研究皮肤瘙痒和痛觉刺激的脊髓处理过程，在戊巴比妥钠麻醉的大鼠中，对宽动态范围型腰段脊髓背角神经元进行了单单位记录。记录了神经元对机械和有害热刺激的反应，以及通过皮内放置的针将组胺（0.01 - 10% = 9×10⁻¹ - 9×10⁻⁴ M）、辣椒素（0.1% = 3.3×10⁻³ M）或其他痛觉化学物质微量注射（1微升）到感受野皮肤内的反应。89个神经元中的大多数（84%）对皮内微量注射组胺有短暂的相位放电反应，随后是持续时间可变（数秒至数分钟）的后放电。皮内注射组胺（而非氯化钠）10分钟后，单位机械感受野低阈值（而非高阈值）部分的平均面积显著增加。然而，组胺注射后对分级压力刺激的反应未受到显著影响。当以5或10分钟的间隔重复注射组胺时，反应未表现出明显的快速耐受。单位反应对浓度跨越4个数量级的组胺微量注射呈剂量相关的显著增加。皮内注射H1拮抗剂西替利嗪后30秒内，在同一皮肤部位注射皮内组胺时的单位反应显著减弱。全身给予吗啡（3.5毫克/千克腹腔注射）后，单位对组胺以及有害热刺激的反应以纳洛酮可逆的方式显著降低。在单位对皮内组胺的持续反应期间，施加机械摩擦、搔抓或有害热刺激会产生短暂而明显的兴奋，随后通常会有一段持续放电减少的时期。单位对组胺的反应在中脑导水管周围灰质的电刺激下明显受到抑制。大多数（79%）测试的组胺反应单位也对皮内微量注射辣椒素有反应。首次微量注射辣椒素后，随后对组胺和辣椒素微量注射的反应显著降低。单位对皮内乙醇（辣椒素溶剂）也呈剂量相关反应，并对80%而非8%的重复皮内乙醇注射表现出快速耐受。对80%乙醇的平均反应明显小于对0.1%辣椒素的反应。所有测试的单位对芥子油（50%）局部应用和皮内5 - 羟色胺（30微克）也有反应。根据试图调和疼痛和瘙痒感觉的心理物理学和临床观察的理论对结果进行了讨论。
