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

The aim of the present study was to examine the effects of the sympathetic co-transmitter Neuropeotide 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. 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. 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. 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. Studies with the Y1-agonist (Leu31, Pro34)-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. In conclusion, these data indicate that Neuropeptide Y affects the excitability of sensory nerve fibre endings. Keywords: Neuropeptide Y, rat, nociception, mechanosensitivity, knee joint, sympathetic nervous system Introduction Neuropeotide Y (NPY) is widely distributed in the central and peripheral nervous system as well as in blood cells (Hokfelt et al., 1998; Ma & Bisby, 1998; Myers et al., 1988). This peptide is able to increase the excitability of neurones (Abdulla & Smith, 1999a,1999b) and is involved in the central modulation of feeding behaviour (Vezzani et al., 1999). NPY is also involved in the central modulation of nociceptive processes in rats and mice. However, excitatory as well as inhibitory effects of this peptide have been obtained (Broqua et al., 1996; Xu et al., 1999). In the peripheral tissue, post-ganglionic sympathetic neurones co-release NPY with norepinephrine, intensifying the vasomotor response (Cortes et al., 1999; Lundberg et al., 1982). Besides this regulatory function, the post-ganglionic sympathetic system also interacts with primary afferents during pathophysiological processes such as nerve injury or tissue trauma (Janig, 1996). While this effect is primarily based on interactions with α-adrenoreceptors, NPY may also affect sensory nerve fibres, as a proportion of dorsal root ganglion neurones exhibit mRNA for different NPY-receptor subtypes (Hokfelt et al., 1998). A well-known in vivo model to study the effect of different mediators on the sensitivity of primary afferents in a peripheral tissue is the knee joint of the rat. Recently, it has been described that the mechanosensitivity of these afferents is modulated by different neuropeptides such as somatostatin, galanin and substance P (Heppelmann et al., 2000; Heppelmann & Pawlak, 1997a,1997b). The knee joint is also supplied with a great number of post-ganglionic sympathetic nerve fibres (Hildebrand et al., 1991), and it has been shown that NPY is present in bone and synovial fluid (Ahmed et al., 1994; Elfvin et al., 1998). In addition, during joint inflammation or rheumatoid arthritis the content of NPY markedly increased (Ahmed et al., 1994; Calza et al., 1998; Elfvin et al., 1998; Larsson et al., 1991). Based on these data, it can be assumed that NPY released from sympathetic nerve fibres may affect the mechanosensitivity of primary afferent units. Therefore, the aim of the present study was to examine the effects of NPY on primary afferent nerve fibres in the rat knee joint. The importance of the different NPY-receptor subtypes was investigated by using specific agonists and antagonists for the Y1- and the Y2-subtype.