W. Grossmann

The effect of morphine on the activity evoked in ventrolateral tract axons of the cat spinal cord.

SummaryThe effect of morphine on the activity in ventrolateral tract axons was studied in intercollicularly decerebrate cats with and without spinal section. Activity was elicited by electrical stimulation of Aδand C-fibres in the sural nerves. In spinal animals, morphine injected intravenously in a dose as low as 0.5 mg/kg reduced the post-stimulus discharge of impulses recorded in ventrolateral tract axons below the site of transection. The depression was not only abolished but reversed by levallorphan and naloxone. Pretreatment with reserpine did not diminish the effect of morphine. The effect of morphine was considerably weaker in decerebrate cats. Reversible block of the spinal cord produced by cold revealed that morphine reduced inhibition from the brain stem controlling the impulse transmission to ventrolateral tract axons.It is concluded that a spinal effect contributes to the analgesic action of morphine.

The dependence of the anti-nociceptive effect of morphine and other analgesic agents on spinal motor activity after central monoamine depletion☆

Abstract The interference of central monoamine depletion with the anti-nociceptive effect of morphine, pethidine and aminophenazone was studied in rats with regard to the changes in spinal motor activity induced by reserpine, tetrabenazine and α-methyl-p-tyrosine. All three analgesic agents prolonged the time of the tail-flick reaction in intact rats. This effect was abolished by reserpine, which prolonged the reaction time. Bilateral lesioning of the substantiae nigrae with microinjections of 6-hydroxydopamine prolonged the reaction time and abolished the anti-nociceptive effect of morphine. In spinal rats, the time of the tail-flick reaction was prolonged by morphine and reduced by aminophenazone. Reserpine did not abolish the effect of morphine in spinal rats. Morphine, pethidine and aminophenazone inhibited the α-reflex discharges facilitated by conditioning stimulation in intact and spinal rats. Pethidine and aminophenazone, but not morphine, depressed the facilitation of α-reflex discharges produced by central monoamine depletion in intact rats. The increase in the amplitude of monosynaptic mass reflexes produced by reserpine in intact rats was not reduced by morphine, whereas the depression of polysynaptic mass reflexes after reserpine was antagonized by morphine. The three analgesic agents differ markedly in their action on spinal motor activity altered by monoamine depletion. It is concluded that the antagonizing effect of central monoamine depletion on the anti-nociceptive effect of morphine, pethidine and aminophenazone in the rat is due to a change in the basal motor activity on which the spinal nociceptive reflex is elicited.

The effect of morphine on mammalian nerve fibres

Abstract The effect of morphine was studied on nerve fibres in the cat sural nerve in situ and in vitro, and on the guinea-pig and rabbit vagus and the guinea-pig phrenic nerves in vitro. Slow intra-arterial administration of morpine (2 mg/kg) to the sural nerve in situ as well as intravenous injection of this dose increased the compound action potential of the Aβ fibres and reduced that of the Aδ and C fibres of the nerve. In the sucrose-gap apparatus, the resting potential and the membrane resistance of the nerves remained unchanged during superfusion with morphine (1 × 10 −4 M). In the cat sural nerve, this concentration of morphine increased the amplitude of the after-hyperpolarization of the compound action potential and the refractory period. The number of spikes discharged by the nerve during the application of long-lasting depolarizing currents was reduced by morphine. The amplitude of the compound action potential and of the after-hyperpolarization of the C fibre compound action potential in the vagus nerves was reduced by morphine, and the relative refractory period was increased in its early phase; calcium deficiency did not change the effect of morphine on the parameters tested in the vagus nerve, apart from the refractory period which was prolonged. Naloxone antagonized the action of morphine. No effect was produced by morphine on the phrenic nerve. The results indicate that morphine acts differently on nerve fibres with different functions.

Inhibition by morphine of repetitive activation of cat spinal motoneurones

Abstract Spinal moto- and interneurones were investigated by means of intra- and extra-cellular microelectrode recording in spinal cats. Morphine (2 mg/kg) and the morphine antagonist levallorphan (0.2 mg/kg) were injected intravenously. The following results were obtained: (1) The action potentials evoked in motoneurones by ventral root stimulation were not changed in amplitude, duration and rates of rise and fall by morphine. 1. (2) Polysynaptic EPSPs elicited in motoneurones by stimulation of the dorsal roots with single pulses were depressed, whereas monosynaptic EPSPs were generally not changed by morphine. The depression of polysynaptic EPSPs produced by morphine was antagonized by levallorphan. 2. (3) The IPSPs evoked in gastrocnemius-soleus motoneurones by sural nerve stimulation were scarcely affected by morphine. 3. (4) The repetitive discharge from interneurones located in the neighbourhood of moto-neurones was reduced by morphine. The reduction of impulse discharges was abolished by levallorphan. The impulse discharge from interneurones situated in dorsal parts of the grey matter of the spinal cord remained unchanged after morphine. 4. (5) Temporal facilitation of EPSPs produced in motoneurones by repetitive stimulation of la afferents from the gastrocnemius-soleus muscles was depressed by morphine. This effect was antagonized by levallorphan. 5. (6) The increase in excitability of the terminals of Ia afferents from the gastrocnemius-soleus muscles produced by repetitive stimulation was depressed by morphine. In the terminals of primary afferents of the sural nerve, the increase in excitability was reduced in duration but not in amplitude. The results obtained are discussed with respect to the inhibition of polysynaptic mass reflexes in spinalized animals, and it is suggested that morphine may influence processes which are generated by repetitive activation.

Depression by morphine of activity in the ventrolateral tract evoked from cutaneous A-fibres.

Abstract In spinal cats, morphine in a dose as low as 0.5 mg/kg depressed the activity evoked in axons of the ventrolateral tract of the spinal cord by stimulation of A-fibers in the sural nerve. This effect was antagonized by levallorphan. The results suggest that a spinal site is involved in the analgesic action of morphine.

The effect of reserpine and DOPA on reflex activity in the rat spinal cord

SummaryThe effect was studied of reserpine and DOPA on ventral and dorsal root responses evoked by stimulation of dorsal roots, gastrocnemius-soleus and sural nerves in intact and spinal rats. Both drugs increased ventral and dorsal root responses, apart from the flexor reflex evoked by sural nerve stimulation which was depressed by reserpine in the intact rat. DOPA, injected after the administration of reserpine, antagonized the effects of the latter drug.The findings suggest that the organization of the pathways involved in the action of reserpine and DOPA differs in rats and cats.

The Site of Action of the Optical Isomers of 1-Methyl-5-Phenyl-5-Propyl Barbituric Acid*

SummaryThe effect of the optical isomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on spinal reflexes and on single motoneurones was studied in spinal animals after intravenous administration.The amplitudes of mono- and polysynaptic reflexes in the rat were reduced by (−)-MPPB (50 mg/kg) and increased by (+)-MPPB (50 mg/kg).(−)-MPPB (25 mg/kg) increased the membrane resistance and the firing level of cat motoneurones and reduced the amplitude of monosynaptic excitatory postsynaptic potentials. (+)-MPPB (25 mg/kg) lowered the membrane resistance and the firing level of the motoneurones and increased the monosynaptic excitatory postsynaptic potentials. Both isomers did not influence significantly the resting potential and the action potentials elicited by antidromic stimulation.It is concluded that the two isomers of MPPB in the doses employed act on post- and presynaptic sites and, moreover, produce their opposite effects (depression or excitation, respectively) by an action on the same neuronal membranes.

The effect of α-methyl-p-tyrosine and substantia nigra lesions on spinal motor activity in the rat☆

The effects of α-methyl-p-tyrosine (αMT) and of bilateral lesioning the substantia nigra on spinal motor activity were studied in rats and compared with reserpine rigidity. αMT, as well as the lesions produced by electrocoagulation or microinjection of 6-hydroxydopamine (6-OH-DA) produced rigidity signalled by tonic activity in the electromyogram during sustained muscle stretch, high α- and low γ-reflex activity, and a short latency of α-reflex discharges. The effect on spinal motor activity of αMT and of bilateral electrocoagulation of the substantia nigra was antagonized by DOPA. Motor disturbances following microinjection of 6-OH-DA into both substantiae nigrae were not influenced by DOPA, metamphetamine or amantadine. Atropine abolished the effect of substantia nigra lesioning by electrocoagulation or by microinjection of 6-OH-DA. On the basis of the results it is concluded that the rigidity produced by reserpine is due to dopamine depletion in the striatum.

The effect of dimethylaminoadamantane on neuronal membranes

The effect of dimethylaminoadamantane (DMAA), an amantadine derivative with an anti-Parkinson property, on rat sensory nerve fibres was studied with the sucrose gap method. DMAA 10(-4) M in normal Locke solution reduced the spike amplitude without changing the resting potential, increased the membrane resistance and depressed repetitive spike activity elicited by depolarizing currents. From experiments performed with changed concentrations of sodium, potassium, calcium and chloride ions in the suspension medium it appears that the permeability of sodium, potassium and chloride ions is reduced by DMAA. The possible implication of the membrane effects of the drug in its action on dopaminergic transmission in the brain is discussed.

The excitatory effect of diphenylthiohydantoin on spinal reflex activity

Abstract The effect of diphenylthiohydantoin (DPTH) 20 mg/kg on spinal reflexes was studied in cats and rats which were spinalized at the lower thoracic level and also in unspinalized rats. DPTH increased the amplitude of mono- and polysynaptic reflex responses in spinal cats and rats. The amplitude of the early component of the afferent volley to peripheral nerve stimulation was enhanced. In unspinalized rats DPTH increased as well as decreased mono- and polysynaptic reflex responses. In spinal cats DPTH increased the number of alpha reflex discharges, but left the number of gamma reflex discharges unchanged. The results are discussed with respect to the conflicting findings obtained by other authors when studying the effect of diphenylhydantoin and DPTH on spinal reflex activity.