Effective spread and timecourse of neural inactivation caused by lidocaine injection in monkey cerebral cortex

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Abstract

We studied the effective spread of lidocaine to inactivate neural tissue in the frontal cortex of the rhesus monkey. Injections of 2% lidocaine at 4 μl/min were made while units were recorded 1 or 2 mm away. To inactivate units 1 mm away from the injection site 100% of the time, 7 μl of lidocaine had to be injected. To inactivate units 2 mm away from the injection site 100% of the time, 30 μl of lidocaine were required. Units were maximally inactivated around 8 min after the start of a lidocaine injection, and they gradually recovered, regaining most of their initial activity by around 30 min after the start of an injection. The volume of lidocaine required to inactivate neurons ≥90% of the time could be estimated by the spherical volume equation, V=4/3 pi (r)3. To prolong the inactivation, a slower infusion of lidocaine subsequent to an initial bolus was effective. Saline control injections had no effect. These results allow both a prediction of the timecourse of neural inactivation and an estimate of the spread of neural inactivation following injection of lidocaine into the monkey cerebral cortex.

Introduction

Neuronal blockade with lidocaine has been used to study a variety of behaviours such as eye movements (Demer and Robinson, 1982; Hikosaka and Wurtz, 1986; Lee et al., 1988; May et al., 1988), drinking (Manani et al., 1995), and the avoidance of noxious stimuli (Urban and Smith, 1994). Lidocaine inactivates neurons by blocking sodium channels (Hille, 1966, Hille, 1977; Ritchie, 1979). A major advantage of using this agent over the more conventional permanent lesion technique is that aside from being reversible, this technique does not have problems with compensatory neuronal effects that arise during many weeks of post-lesion recovery (Hikosaka and Wurtz, 1986).

The effective spread of lidocaine and its timecourse of effect has not been studied systematically for different volumes in the cerebral cortex. We injected different volumes of lidocaine into the dorsomedial frontal cortex of an awake monkey while recording from neurons at different distances away from the injection site. The effective spread of lidocaine conformed to the cubic relationship, volume=4/3 pi (radius)3.

Section snippets

Subject

One adult rhesus monkey (Macaca mulatta) was used. Throughout this study food and water were freely available. After testing each day, the animal was returned to the vivarium. The monkey was provided for in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the guidelines of the Massachusetts Institute of Technology Committee on Animal Care.

Surgery

The monkey was anesthetized first with ketamine (10 mg/kg) and then with pentobarbital (30 mg/kg) in

Effective spread

The injection sites are depicted in Fig. 1. The injection depths that were used, at which neurons had acceptably stable and vigorous firing rates, ranged from 0.5 to 1.5 mm below the first unit encountered on a descent. Baseline firing frequencies ranged from 10 to 50 Hz. Within minutes of the start of a lidocaine infusion, the neural firing rate dropped rapidly (Fig. 3A,B). After that, the neural activity gradually recovered. Although eight or so injections of agent were made at the same

Temporal properties

Neuronal shutdown following an injection of lidocaine into the dorsomedial frontal cortex was immediate, occurring within 5 min of starting an injection and recovering within 30 min. These finding coincide with previous studies where oculomotor (Demer and Robinson, 1982; May et al., 1988) and evoked potential (McGee et al., 1991) measures were used to assess the onset of an effect of lidocaine and recovery thereof. Anywhere from 1 to 30 μl of lidocaine were injected in these studies, volumes

Acknowledgements

This work was supported by NIH EY08502 to P.H. Schiller.

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