Arthur Taub

Lamina-specific suppression of dorsal-horn unit activity by morphine sulfate.

The effects of morphine sulfate on single-unit activities of various dorsal-horn Rexed laminae were studied using an extracellular microelectrode recording technique in decerebrate spinal cats. Morphine sulfate, 0.5, 1, and 2 mg/kg, iv, suppressed in a dose-related manner spontaneous single-unit activities in Rexed laminae I and V, known to respond principally to noxious stimuli, but did not affect spontaneous activities in laminae IV and VI, known to respond to non-noxious stimuli. Morphine sulfate, I mg/kg, iv, also suppressed unit activities of laminae I and V evoked by noxious cutaneous stimuli by 35.5 ± 7.1 and 48.2 ± 4.0 (&OV0335; ± 1 SE) per cent, respectively. The selective action of morphine on dorsal horn nociceptors may partially explain the analgesic action of morphine at the spinal level.

Lamina-specific Suppression of Dorsal-horn Unit Activity by Ketamine Hydrochloride

The effects of ketamine hydrochloride on single-unit activities of various dorsal-horn Rexed laminae were studied with an extracellular microelectrode recording technique in decerebrate spinal cats. Ketamine hydrochloride, 2.5 mg/kg, iv, suppressed spontaneous single-unit activities of laminae 1 and 5 by 23 and by 43 per cent, respectively, while spontaneous activity of lamina 4 and that of lamina 6 were not significantly affected. This dose suppressed evoked unit activities of laminae 1 and 5 by 44 and by 64 per cent, respectively. As laminae 1 and 5 are known to respond principally to noxious stimali, a partial explanation for the analgesic effect of ketamine may be lamina-specific suppression of neuronal activity.

The effect of diphenylhydantoin on self-mutilation in rats produced by unilateral multiple dorsal rhizotomy

It has been reported that self-mutilation of forelimbs in rats following multiple cervicothoracic dorsal rhizotomy may be dependent on the integrity of specific ascending spinal pathways. This behavior may arise from central dysfunction rather than as a direct result of limb anesthesia. Such a hypothesis would be supported if self-mutilation after dorsal rhizotomy were an aggressive act and if it were reduced by diphenylhydantoin. Thirty female albino rats underwent multiple unilateral cervicothoracic dorsal rhizotomy from C5 to T1 and were randomly assigned to treatment with 10, 15, 25, and 50 mg/kg diphenylhydantoin intraperitoneally each day. Some animals received the drug vehicle alone as a control, and some animals were handled as the others but not treated. Videotape techniques were usd to confirm and study the mutilation process, which appeared to be an aggressive rather than a passive one. Spinal cord histology was obtained. Diphenylhydantoin was shown to reduce the incidence of self mutilation from 89% (9 animals) to 40% (15 animals) when given at doses greater than 10 mg/kg/day. The results support a possible etiologic role of central dysfunction and suggest that this process may involve hyperactive afferent pathways.

An Analgesic Action of Intravenously Administered Lidocaine on Dorsal-horn Neurons Responding to Noxious Thermal Stimulation

Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. Spontaneous discharge frequencies at maximum suppression, observed 3--7 min after administration of each of the three doses of lidocaine were 64 +/- 14 (mean +/- 1 SE), 32 +/- 8, and 25 +/- 9 per cent of control values, respectively; responses to noxious thermal stimuli were 83 +/- 5, 52 +/- 8, and 39 +/- 7 per cent of the control values, respectively. Threshold skin temperature to noxious thermal stimulation increased from 44.7 +/- 0.4 C (control) to 46.3 +/- 0.7 C with lidocaine, 5 mg/kg (P less than 0.05), to 47.8 +/- 0.8 C with lidocaine, 10 mg/kg (P less than 0.01). The times necessary for recovery varied in a dose-related fashion. Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons.

Evoked bulbar reticular unit activity following delta fiber stimulation of peripheral somatosensory nerve in cat

Abstract Evoked responses of neurons located in the nucleus reticularis gigantocellularis and lateral tegmental field of the medulla in 30 cats anesthetized with a mixture of 75% nitrous oxide and 25% oxygen were studied following electrical stimulation of peripheral somatosensory nerves. Single, and trains of multiple stimuli were applied above threshold levels for A-beta-delta fiber activity and the responses of 93 units in the nucleus reticularis gigantocellularis and 28 units in the lateral tegmental field were analyzed with respect to latency, duration, frequency, and afterdischarge. The adequate stimulus for altering unit activity was shown to be stimulation above A-beta-delta threshold. Multiple stimuli in the A-beta-delta range produced a more intense and longer response than single stimuli. A somatotopic organization suggesting predominantly contralateral input as well as predominantly upper extremity input was demonstrated but there was bilateral representation of all four extremities in the caudal nucleus gigantocellularis. Stimulation of the peripheral nerves of the four extremities had no effect on the activity of neurons in the adjacent lateral tegmental field.

Effects of ketamine on nociceptive cells in the medial medullary reticular formation of the cat.

Anatomic, physiologic and behavioral evidence suggests that the neurons in the nucleus reticularis gigantocellularis of the medial medullary reticular formation may act as a relay station for the transmission of nociceptive information from the spinal cord to higher brain centers. The nucleus reticularis gigantocellularis may also be the site of action of analgesic agents, such as ketamine hydrochloride. Utilizing extracellular microelectrodes in 23 decerebrate cats, the authors measured the effect of ketamine on neurons in the nucleus reticularis gigantocellularis that were excited by electrical stimulation of peripheral nerves. The frequency of spontaneous single-unit firing activity in the nucleus reticularis gigantocellularis was suppressed by 31 ± 11 (&OV0335; ± I SE) and by 62 ± 7 per cent with ketamine, 1.0 and 2.5 mg/kg, iv, respectively. The frequency of evoked single-unit activity was suppressed by 57 ± 9 and 79 ± 5 per cent with ketamine, 1.0 and 2.5 mg/kg, respectively. Ketamine produces significant depression of single-unit activity of the cells in the nucleus reticularis gigantocellularis, suggesting that this may be an important site of its analgesic action.

Identification of central trigeminal nociceptors and the effects of nitrous oxide.

Physiologic and pharmacologic properties of the nucleus caudalis of the trigeminal complex were studied using an extracellular microelectrode recording technique in unanesthetized, mechanically ventilated, decerebrate cats after removal of the neural arch of the first cervical spine. Central trigeminal nociceptors were identified in the magnocellularis portion of the dorsal horn of the first cervical segment of the spinal cord. This finding resolved an apparent “paradox” reported previously. Cells responding to low-threshold cutaneous stimuli applied to the ipsilateral face were found dorsal and rostral to the central trigeminal nociceptors. Nitrous oxide (75 per cent) suppressed the spontaneous firing frequency of the central trigeminal nociceptors by 31-35 per cent, but facilitated spontaneous activity of the low-threshold cutaneous receptors of the nucleus caudalis by 20-31 per cent. The differential effects of nitrous oxide on trigeminal neurons were analogous to the effects of nitrous oxide on the nuclear aggregates of the dorsal horn of the feline lumbar spinal cord.

Dorsal Root Ganglionectomy for Intractable Monoradicular Sciatica

Dorsal root ganglionectomy was introduced in 1975 as a procedure with theoretical advantages over dorsal rhizotomy for the treatment of intractable radicular pain. Results of the few clinical reports have been generally favorable. The authors report the largest and most comprehensively studied series to date. 61 patients (33 men, 28 women) underwent dorsal root ganglionectomy for intractable sciatica, most often monoradicular. Patients were selected for surgery only if the clinical history, physical examination, radiologic studies, and diagnostic radicular block all predicted a favorable outcome. Sciatica was markedly reduced or eliminated in 36 patients (59%). Dysesthesia following ganglionectomy was observed frequently, but not invariably (approximately 60% of cases). Dysesthesia was generally of mild or moderate severity, self-limited, and responsive to treatment.

Effects of morphine on the rexed lamina VII spinal neuronal response to graded noxious radiant heat stimulation.

Abstract Morphine sulfate exerts its analgesic action in part through suppression of the activity of spinal cord nociceptive neurons. Cells in Rexed lamina VII are considered to be the cells of origin of the spinothalamic and spinoreticular tracts concerned with nociception. Using graded radiant heat to their peripheral receptive fields, the relationship between the intensity of heat (millicalories per square centimeter per second) which produces noxious stimuli and the response frequency of single units in Rexed lamina VII of the spinal cord was analyzed with extracellular microelectrode recording techniques in 15 decerebrated and spinal-transected cats before and after administration of morphine sulfate (1 mg/kg, iv). A linear relationship between the intensity of heat and the frequency of response discharge was observed (above threshold) both in the control study and after the administration of morphine. Morphine sulfate significantly suppressed the spontaneous activity of the units studied, raised the threshold of their evoked activity to varying intensities of heat, and diminished the slope of the heat intensity vs evoked single-unit response relationship. Naloxone (0.02 mg/kg, iv) eliminated all changes brought about by morphine sulfate.

Lamina-specific suppression and acceleration of dorsal-horn unit activity by nitrous oxide: a statistical analysis.

The effect of 75 per cent nitrous oxide–oxygen upon the spontaneous unit activity of cells in Rexed laminae IV, V, and VI of the dorsal horn of spinal cats was analyzed quantitatively with the aid of several digital computer programs. Overall statistical parameters, interval histograms, and burst-interval histograms were derived. Each cell lamina was characterized by a “statistical signature.” The spontaneous activity of lamina IV cells remained unaffected by the gas. The spontaneous activity of lamina V cells showed an increase in mean interval, accounted for by an increase in interburst interval, with relative maintenance of intraburst interval duration. The spontaneous activity of lamina VI cells was increased in rate and regularized in pattern. The cellular effects of analgesic agents cannot be described by overall statistical parameters alone, but require specification of the interval “fine structure” of spontaneous unit activity.