Changes in glycinergic neurotransmission in the spinal cord dorsal horn are critically involved in the development of pathological
pain. Since the concentration of
glycine in the synaptic cleft is controlled by specialized
proteins, the
glycine transporters GlyT1 and GlyT2, manipulation of this system might have significant effects on nociception. In the present study, we investigated the effects of the spinally applied
glycine transporter inhibitors
ALX 5407 (GlyT1) and
ALX 1393 (GlyT2) on nociceptive behavior in the chronic constriction injury model of
neuropathic pain in male Wistar rats. After implementation of neuropathy, the animals were injected with three dosages of
ALX 5407 and
ALX 1393 (10, 50 and 100 microg) via an intrathecal
catheter (n = 8 each). Subsequently, nociceptive behavior was evaluated regarding
thermal hyperalgesia (Hargreaves method) and mechanical sensitization (von Frey filaments) over 240 min after application. Inhibition of GlyT1 by
ALX 5407 had differential dose-dependent effects. While the highest and the lowest concentrations were antinociceptive, the medium dose evoked pronociceptive effects. The GlyT2 inhibitor
ALX 1393 was only effective in the highest concentration at which it exerted significant antinociception. However, in the same dose,
ALX 1393 caused remarkable side effects such as
respiratory depression and motor deficits in three animals. Our findings indicate that inhibition of
glycine transporters is capable of evoking significant effects on nociceptive behavior in
neuropathic pain. Whether
glycine transporter inhibitors have the capability to gain clinical relevance as
analgesic compounds on the long run has to be elucidated in further investigations.