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-t ype primary afferent fibre terminals of the small dorsal root ganglion (DRG) neurons, play important roles in spinal nociception. By means o f nonradioactive in situ hybridization and whole-cell recording, we sh owed that the small rat DRG neurons also express the NK-I tachykinin r eceptor. In situ hybridization demonstrated that the positive neurons in rat DRG sections were mainly small cells (85.9%) with diameters les s 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 (d iameters >40 mu m) were observed. Expression in small DRG neurons (dia meter <21 mu m) was confirmed by in situ hybridization of isolated cel ls, which were demonstrated to express NK-1 receptor mRNA at a very hi gh frequency (>90% of small DRG neurons) and therefore were subjected to whole-cell recording, In 57 of 61 cells recorded, SP or the selecti ve 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 d uration of 0.5-2 h. These currents were blocked by co-application of t he 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 record ing and cell-attached single-channel recording demonstrated that the l ong-lasting response was due to the opening of a channel with an inwar d current. Employment of non-Ca2+ and Ca2+ + choline solutions reveale d that this channel might be a Ca2+-permeable, non-selective cation ch annel. The prolonged NK-1 tachykinin response exhibited extreme desens itization. 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.