Neuropeptide Y changes the excitability of fine afferent units in the rat knee joint

Abstract

1. The aim of the present study was to examine the effects of the sympathetic co-transmitter Neuropeptide Y on primary afferent nerve fibres of the rat knee joint. The responses to passive joint rotations at defined torque were recorded from 41 slowly conducting afferent nerve fibres (0.9 - 18.8 m s(-1)) innervating the knee joint capsule. 2. About 70% of the joint afferents were significantly affected in their mechanosensitivity by topical application of Neuropeptide Y. Significant effects occurred at a concentration of 10 nM. 3. Decreased mechanosensitivity was observed in about 40% of nerve fibres, whereas 30% of the units increased the mechanosensitivity. In addition, in about 35% of the fibres resting activity was induced or increased. Neither the conduction velocity nor the mechanical threshold of the units correlated with the described effects of Neuropeptide Y. 4. NPY(13--36), a specific Y2-receptor agonist, only modulated the mechanosensitivity, with no effect on the resting activity. The effects on the mechanosensitivity were similar to Neuropeptide Y, i.e. increase and decrease of the response. 5. Studies with the Y1-agonist (Leu(31), Pro(34))-NPY showed that activation of the Y1-receptor predominantly resulted in an enhanced mechanosensitivity and an induction or increase of a resting activity. The opposite effect was observed by application of BIBP 3226 BS, a Y1-receptor antagonist. 6. In conclusion, these data indicate that Neuropeptide Y affects the excitability of sensory nerve fibre endings.

Figure 1

Different effects of NPY on afferent nerve terminals. Examples of units are shown in which NPY lead to an increased (A) or decreased (B) mechanosensitivity in a dose dependent manner. Change of the responses at a torque of 10 mNm above the mechanical threshold are presented as the mean±s.e.mean of the units with a significant increase and a significant decrease of the responses as percentage of the average control level that were set at 100% (C). The mean response of all units tested is presented as dots.

Figure 2

Change of the mechanosensitivity after application of 100 nM NPY in dependence of the threshold of the unit. The respective NPY-effect was independent of the threshold and the classification of the afferent unit.

Figure 3

Induction of a resting activity by a topical application of 100 nM NPY. The mechanosensitivity of this unit was slightly reduced at the same time.

Figure 4

Summary of the effect of NPY, the Y1- and the Y2-receptor agonist on the mechanosensitivity and resting activity of the examined nerve fibre ending. The effects of NPY and (Leu³¹, Pro³⁴)-NPY (Y1) and NPY(13 – 36) (Y2) on the excitability of afferent knee joint units were tested. The percentage of units with no change (0, white), with increase (+, cross-hatched), and decrease (−, hatched) is represented.

Figure 5

Effect of BIBP 3226 BS on the mechanosensitivity. In 3 of 10 units the mechanosensitivity was significantly reduced after topical application of BIBP 3226 BS. The effect was antagonized by topical application of (Leu³¹, Pro³⁴)-NPY. Changes of the responses at a torque of 10 mNm above the mechanical threshold is presented as the mean±s.e.mean. The response to control movements was defined as 100%.