ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
The tachykinins substance P (SP) and neurokinin A, released by the C-type primary afferent fibre terminals of the small dorsal root ganglion (DRG) neurons, play important roles in spinal nociception. By means of non-radioactive in situ hybridization and whole-cell recording, we showed that the small rat DRG neurons also express the NK-1 tachykinin receptor. In situ hybridization demonstrated that the positive neurons in rat DRG sections were mainly small cells (85.9%) with diameters less than 25 μm. The remaining positive neurons (14.1%) were cells with medium diameters between 26 and 40 μm. No positive large neurons (diameters 〉 40 μm) were observed. Expression in small DRG neurons (diameter 〈 21 μm) was confirmed by in situ hybridization of isolated cells, which were demonstrated to express NK-1 receptor mRNA at a very high frequency (〉 90% of small DRG neurons) and therefore were subjected to whole-cell recording. In 57 of 61 cells recorded, SP or the selective NK-1 receptor agonist [Sar9, Met(O2)11]SP (Sar-SP, 1 or 2 μm) produced a delayed vibrating inward current (50–300 nA) with a long duration of 0.5–2 h. These currents were blocked by co-application of the NK-1 receptor antagonist L-668, 169 (1 μm), but were not affected by the NK-2 antagonistL-659, 877 (2 μm). Both current-clamp recording and cell-attached single-channel recording demonstrated that the long-lasting response was due to the opening of a channel with an inward current. Employment of non-Ca2+ and Ca2+ + choline solutions revealed that this channel might be a Ca2+-permeable, non-selective cation channel. The prolonged NK-1 tachykinin response exhibited extreme desensitization. This work suggests that presynaptic NK-1 autoreceptors may be present on the primary afferent terminals in the spinal cord, where they could contribute to the chronic pain and hyperalgesia.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1460-9568.1998.00140.x
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