Adelson D, Lao L, Zhang G, Kim W, Marvizón J C G
Veterans Affairs Greater Los Angeles Healthcare System, Building 115, Room 119, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
Neuroscience. 2009 Jun 30;161(2):538-53. doi: 10.1016/j.neuroscience.2009.03.058. Epub 2009 Mar 29.
Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1-10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Adelta-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli.
初级传入神经的放电频率以及背角神经元中神经激肽1受体（NK1R）的内化均随伤害性刺激强度的增加而升高。因此，我们研究了初级传入神经的放电模式如何影响NK1R的内化。在大鼠脊髓切片中，对背根进行电刺激可通过诱导初级传入神经释放P物质，从而引起I层神经元中NK1R的内化。刺激频率对NK1R的内化有显著影响，内化在100Hz时增加，然后在200Hz时突然下降。肽酶抑制剂在低于30Hz的频率下可增加NK1R的内化，这表明肽酶在中等放电频率下会限制P物质与受体的结合。在所有频率下，NK1R的内化均随脉冲数量的增加而增加，但在1-10Hz时的最大内化程度明显低于30Hz时。成串的脉冲所产生的NK1R内化与持续30Hz刺激所产生的相同。为了确定高刺激频率下诱导释放的P物质是否来自C纤维，我们记录了麻醉大鼠坐骨神经中的复合动作电位。当以引起C波抬高的强度进行刺激时，我们观察到大量的NK1R内化，但以仅引起Aδ波抬高的强度刺激时则未观察到。频率高达100Hz的串刺激中的每个脉冲均引起C波抬高，这表明C纤维能够跟上这些高频。随着刺激频率的增加，C波抬高的幅度逐渐下降，这可能是由包括时间离散在内的多种因素共同作用所致。总之，C纤维中的瞬时放电频率决定了伤害性刺激释放的P物质的量。
