Small sensory neurons in the rat dorsal root ganglia express functional NK-1 tachykinin receptor

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 nonradioactive in situ hybridization and whole-cell recording, we showed that the small rat DRG neurons also express the NK-I 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 mu m. The remaining positive neurons (14.1%) were cells with medium diameters between 25 and 40 mu m. No positive large neurons (diameters >40 mu m) were observed. Expression in small DRG neurons (diameter <21 mu m) 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 [Sar(9), Met(O2)(11)]SP (Sar-SP, 1 or 2 mu M) 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 mu M), but were not affected by the NK-2 antagonist L-659, 877 (2 mu M). 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.