Single neurons were recorded in cat primary visual cortex, and the effect of iontophoresis of the metabotropic glutamate agonist 1S,3R-aminocyclopentane-1.3-dicarboxylic acid (ACPD) was observed. In nearly all cases (41/43), ACPD reduced the visual response. In some cases ACPD also reduced spontaneous activity (24/43), and in other cases ACPD increased spontaneous activity (18/43). Increases were generally seen in infragranular layers (V and VI), and decreases in supragranular layers (II and III). The reduction in the visual response was also largest in supragranular layers. We conclude that activation of metabotropic glutamate receptors has both facilitatory and depressive effects in visual cortex, and the effect depends on the layer of the cell recorded.

In visual neurones of the superficial layers of the superior colliculus (SSC), repetitive stimulation causes a progressive decline in the size of the response to the stimulus, usually known as response habituation or response adaptation. A mechanism has been proposed in which habituation results from coactivation of excitatory and inhibitory neurones, and the responses of the inhibitory neurones block the response to subsequent stimulus presentations. Excitatory amino acid (EAA) neurotransmitters mediate visual responses via NMDA and non-NMDA receptors in cat SSC. We have investigated the role of these receptors in the generation of response habituation. Following the iontophoretic application of the EAA antagonists CNQX, APS or CPP, repetitive visual stimulation paradigms which normally produce response habituation no longer do so. Indeed the response to each presentation of the stimulus is similar. Intravenous administration of the dissociative anesthetic ketamine (2–10 mg/kg) had similar actions to iontophoretically applied NMDA antagonists. The data imply that intracollicular mechanisms activated by NMDA and non-NMDA receptors contribute to the generation of the inhibitory responses in SCC which lead to response habituation. Furthermore, the effects seen with ketamine anesthesia suggest that the use of ketamine in studies of sensory systems may result in the lack of habituation.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. We tested the actions of iontophoretically applied GABAergic ligands on the spontaneous and stimulus-evoked activity of retinal ganglion cells recorded extracellularly in the in vivo cat eye.

GABA as well as GABAA receptor agonists inhibited all brisk ganglion cell types. This action was antagonized by bicuculline. Bicuculline on its own increased the activity of ON-ganglion cells but suppressed OFF-ganglion cells. This suppression effect was abolished during the blockade of glycinergic transmission by strychnine.

The GABAB receptor agonist baclofen inhibited OFF-ganglion cells whereas the activity of ON-ganglion cells was either increased or decreased depending on the stimulus contrast. The antagonists, phaclofen and 2-hydroxy saclofen, produced opposite effects to baclofen and antagonized its action.

The present study demonstrates that both GABAA and GABAB receptors modulate the activity of ON- and OFF-ganglion cells in the cat retina.

Survey results continue to reveal that postoperative pain is insufficiently managed throughout Europe and the rest of the world. However, the efficient use of existing resources, as well as the introduction of novel technologies, may aid in its improvement. Use of an acute pain service has the potential to improve pain management through specialized patient care and utilization of effective analgesic techniques. Multimodal analgesic techniques, which include adjuvant non-opioids and/or regional analgesic techniques, can provide effective analgesia and reduce the amount of systemic opioids (or obviate the need) for postoperative pain management. Patient-controlled analgesia modalities may also offer improvements to pain management, as in practice they provide pain relief superior to the intermittent administration of bolus doses of opioids. A novel patient-controlled analgesia modality that has been approved by the European Medicines Evaluation Agency (EMEA) for the treatment of acute, moderate-to-severe pain is the needle-free, pre-programmed fentanyl HCl iontophoretic transdermal system. This system was shown in a recent US clinical trial to be comparable in efficacy to a standard regimen of morphine intravenous patient-controlled analgesia. Adverse events associated with the use of the fentanyl iontophoretic transdermal system are generally similar to those experienced by patients using intravenous morphine patient-controlled analgesia. Considerations regarding the selection of patients for treatment with the fentanyl iontophoretic transdermal system are similar to those with other patient-controlled analgesia modalities; sufficient upper limb mobility and alertness are required to operate the system. Utilization of the fentanyl iontophoretic transdermal system, together with the guidance of an effective acute pain service, may lead to improvements in postoperative pain management.

Background and objective: Pain following the injection of propofol is a common problem. It is often treated by the coadministration of intravenous lidocaine. Iontophoresis, which facilitates the delivery of charged molecules such as lidocaine to body tissues, may be a practical alternative to lessen the pain.

Methods: The iontophoretic application of lidocaine was compared with intravenous lidocaine to assess the relative efficacy of reducing pain during propofol administration.

Results: The incidence rate of moderate or severe pain was significantly greater in the iontophoresis group (26.7 compared with 6.9% in the intravenous lidocaine group) (P < 0.05).

Conclusions: The iontophoretic administration of lidocaine 60 mg does not compare favourably with lidocaine 40 mg mixed with propofol for the reduction of pain on administration of propofol.

In the rat, the superficial gray layer (SGS) of the superior colliculus receives glutamatergic projections from the contralateral retina and from the visual cortex. A few fibers from the ipsilateral retina also directly innervate the SGS, but most of the ipsilateral visual input is provided by cholinergic afferents from the opposing parabigeminal nucleus (PBG). Thus, visual input carried by cholinergic afferents may have a functional influence on the responses of SGS neurones. When single neuronal extracellular recording and iontophoretic drug application were employed to examine this possibility, cholinergic agonists were found to depress responses to visual stimulation. Lobeline and 1-acetyl-4-methylpiperazine both depressed visually evoked activity and had a tendency to reduce the background firing rate of the neurones. Carbachol depressed the visual responses without any significant effect on the ongoing activity, while the muscarinic receptor selective agonist methacholine increased the background activity of the neurones and reduced their visual responses. Lobeline was chosen for further studies on the role of nicotinic receptors in SGS. Given that nicotinic receptors are associated with retinal terminals in SGS, and that the activation of presynaptic nicotinic receptors normally facilitates transmitter release (in this case glutamate release), the depressant effects of nicotinic agonists are intriguing. However, many retinal afferents contact inhibitory neurones in SGS; thus it is possible that the increase in glutamate release in turn facilitates the liberation of GABA which goes on to inhibit the visual responses. We therefore attempted to reverse the effects of lobeline with GABA receptor antagonists. The depressant effects of lobeline on the visual response could not be reversed by the GABAA antagonist bicuculline, but the GABAB antagonist CGP 35348 reduced the effects of lobeline. We hypothesize that cholinergic drive from the parabigeminal nucleus may activate presynaptic nicotinic receptors on retinal terminals, thereby facilitating the release of glutamate onto inhibitory neurones. Consequently GABA is released, activating GABAB receptors, and thus the ultimate effect of nicotinic receptor activation is to depress visual responses.