Administration of opiate antagonist naloxone induces recurrence of increased jaw muscle activities related to inflammatory irritant application to rat temporomandibular joint region.

1. Our recent studies in rats have demonstrated that the small-fiber excitant and inflammatory irritant mustard oil injected into the temporomandibular joint (TMJ) region can evoke a sustained and reversible increase of electromyographic (EMG) activity in jaw muscles and an acute inflammatory response. The aim of the present study was to test if opioid mechanisms are involved in modulating the EMG increase evoked by mustard oil. 2. Mustard oil injected into the rat TMJ region evoked significant increases of jaw muscle EMG activity; the vehicle mineral oil had no such effect. The increased EMG activity lasted up to 20 min, and by 30 min after the mustard oil injection had returned to control (preinjection) levels, at which time administration of the opiate antagonist naloxone (1.3 mg/kg i.v.) induced a significant recurrence of the increase in EMG activity. This "rekindling" of EMG activity appeared at 5 to 10 min after the naloxone administration and lasted for 10 to 20 min. In contrast, naloxone administration in the animals receiving mineral oil injection into the TMJ region did not "rekindle" the EMG activity, nor did the administration of the peripherally acting opiate antagonist methylnaloxone or the vehicle of naloxone. 3. These findings reveal that the application of the opiate antagonist naloxone produces a recurrence of increased jaw muscle activity reflexively evoked by mustard oil injection into the rat TMJ region. They suggest that central opioid depressive mechanisms activated by the mustard oil-induced afferent barrage limit the duration of the evoked EMG changes.

A comparison of anesthetic agents and their effects on the response properties of the peripheral auditory system.

Anesthetic agents were compared in order to identify the most appropriate agent for use during surgery and electrophysiological recordings in the auditory system of the tokay gecko (Gekko gecko). Each agent was first screened for anesthetic and analgesic properties and, if found satisfactory, it was subsequently tested in electrophysiological recordings in the auditory nerve. The following anesthetic agents fulfilled our criteria and were selected for further screening: sodium pentobarbital (60 mg/kg); sodium pentobarbital (30 mg/kg) and oxymorphone (1 mg/kg); 3.2% isoflurane; ketamine (440 mg/kg) and oxymorphone (1 mg/kg). These agents were subsequently compared on the basis of their effect on standard response properties of auditory nerve fibers. Our results verified that different anesthetic agents can have significant effects on most of the parameters commonly used in describing the basic response properties of the auditory system in vertebrates. We therefore conclude from this study that the selection of an appropriate experimental protocol is critical and must take into consideration the effects of anesthesia on auditory responsiveness. In the tokay gecko, we recommend 3.2% isoflurane for general surgical procedures; and for electrophysiological recordings in the eighth nerve we recommend barbiturate anesthesia of appropriate dosage in combination if possible with an opioid agent to provide additional analgesic action.

A spirohydantoin derivative of oxymorphone: an agonist with delayed antagonist activity.

We have synthesized a novel derivative of oxymorphone, oxymorphone-6 alpha-spirohydantoin. The derivative was less toxic in mice than the parent compound and it showed a significant anticonvulsive activity. It exerted agonist effects in doses lower than those of morphine and its agonist effects were longer lasting. Furthermore, both oxymorphone and the 6-spirohydantoin showed definite antagonist properties 48 hr later: they prevented analgesic effects of morphine. The antagonist effects of the derivative persisted for a week.