The spinal cord as a major site for the antinociceptive action of nicotine in the rat.

These studies were conducted to localize the antinociceptive action of nicotine within the CNS. Antinociceptive and biodispositional studies were carried out after the injection of [3H]nicotine subcutaneously and intracerebroventricularly into the common carotid and vertebral arteries and into the subarachnoid space. The data indicated that [3H]nicotine was most potent when given into the subarachnoid space than by any of the other route of administration. Further, the disposition studies showed that [3H]nicotine was almost entirely contained in the thoracic and lumbar areas. These results are consistent with the hypothesis that the spinal cord is an important site for antinociception induced by nicotine.

The effect of hypophysectomy on acupuncture analgesia in the mouse.

Acupuncture analgesia was quantitated in the phenylquinone induced writhing test in mice. Both manual acupuncture and electroacupuncture significantly reduced the number of writhes, i.e. 47% and 51% reduction respectively. Naloxone (2 mg/kg) pretreatment abolished this antinocicpetive effect suggesting that an endogenous opiate-like substance was involved. Hypophysectomy did not alter the electroacupuncture induced inhibition of writhing. These results confirm previous reports that acupuncture causes the release of an endogenous substance(s) with opioid activity, but disagree with previous reports in that our data show that the hypophysis is not involved in the release of this endogenous opiate or in any other mechanism of acupuncture analgesia in the mouse.

Distribution of thalamic nociceptive neurons activated from the tail of the rat.

The purpose of the present study was to map systematically in the thalamus the distribution of neurons processing nociceptive information from the tail of the rat. Pentobarbital-anesthetized and gallamine-paralyzed rats were used. Glass microelectrodes were used to record extracellularly from thalamic neurons. Noxious radiant heat stimuli were applied to the tail with a tail-flick apparatus, and the recorded neurons were localized with horseradish peroxidase deposits or by marking electrodes left in situ. A number of 121 neurons were tested of which 45 responded. Of these, 13 were located in the ventrobasal complex (VB), 17 were located in the central lateral nucleus and the parafascicular nucleus of the intralaminar nuclei (ILN). The rest of the responding neurons were located in the posterior group, the reticular thalamic nucleus, and the zona incerta. The nucleus submedius was not examined specifically. It is concluded that the VB and the ILN are two of the most important thalamic nuclei for processing nociceptive information from the tail of the rat.

Contralaterally induced dorsal root reflex shares common final pathway with ipsilaterally elicited ones in Wistar rats.

The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal root central stump, initiated by sciatic nerve (SN) stimulation (St), was studied in anesthetized rats. Both ipsi- and contralateral Sts elicited DRR, with central delays of 4.6 +/- 0.3 (n = 10) and 27.3 +/- 2.5 (n = 5) ms, respectively. Ipsilaterally induced DRRs showed repetitive firing (mean = 3 +/- 0.5 spikes, n = 5), while contralaterally induced ones were abolished after spinalization (T13). When the time interval between two ipsilateral suprathreshold Sts was less than 12 +/- 2.4 ms (n = 12), the second DRR was abolished. On the other hand, when it between two ipsilateral subthreshold Sts was less than 4.8 +/- 0.3 ms (n = 7), DRR was activated. Contralaterally induced DRR also showed temporal inhibition and facilitation with time intervals similar to that in ipsilateral cases. Furthermore, when the latency between a contralaterally and a ipsilaterally induced DRR was less than 10.8 +/- 1.8 ms (n = 5), the later DRR was blocked by the former, and vice versa. Facilitation can be also shown by a contralateral and a ipsilateral subthreshold St. These results suggested that contralaterally induced DRRs may share part of final common pathway with ipsilaterally induced ones.

Can antidromic stimulation of rat muscle afferents modulate the sensitivity of muscle spindles?

The sensitivity of muscle spindles in gastrocnemius-soleus (GS) muscles following dorsal root (DR) antidromic stimulation (ASt) was investigated in anesthetized rats, in which the hindleg was totally denervated except the GS muscle, ventral roots from L3 to S1 and DRs from L4 to L6, which were severed after laminectomy. The peripheral end of a teased DR filament with single unit tonic discharges from a constantly stretched muscle spindle were recorded and antidromically stimulated after identification. In response to ASt with various frequencies, two different types of ending were found: (1) type I, its tonic discharge was not altered following ASt at 100 Hz for 10 s, while type II was significantly inhibited even at a frequency of 50 Hz; (2) at 300 Hz, both types of endings were inhibited, however, type I recovered in less than 4 s, while type II took more than 15 s to return to control level, and a silent period (1-5 s) was found in type II but not in type I; (3) the effective minimum inhibitory frequency for type I and type II was 200 and 50 Hz, respectively. These results suggest that type I and type II endings may correspond to the primary and the secondary endings of the muscle spindle whose sensitivity may be modulated antidromically by the dorsal root reflex.

Which afferents induce and transmit dorsal root reflex in rats?

The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal root central stump, initiated spontaneously or by electric stimulation (St) of sciatic nerve, was studied in anesthetized rats. The excitation of group II afferents were the major inputs to induce DRRs which were transmitted mainly in fibers with conduction velocity below 20 m/s, and its central delay was 3-5 ms. The firing frequency of both spontaneous and evoked DRRs were increased two to four times after spinalization (T13). These results suggested that the DRR may play an important role in the modulation of sensory afferent inputs regulated by supraspinal structures.

Effect of electroacupuncture on blood pressure and adrenal nerve activity in anesthetized rats.

The neural mechanism underlying the effect of electroacupuncture (Ea) on arterial blood pressure (BP) and adrenal nerve activity (ANA) was investigated in anesthetized rats. Tsusanli (St-36) and Hoku (Li-4) were tested with combinations of two different frequencies (3 and 30 Hz) with various stimulation intensities of Ea. At Tsusanli, no effect was found, while at Hoku, an elevation of BP in parallel with ANA was elicited during Ea when the intensity was 5xT or higher. The pattern of the pressor response caused by the low frequency Ea (LFEa, 3 Hz) was a tonic one, while a phasic one was induced by the high frequency Ea (HFEa, 30 Hz). When both Hoku were simultaneously stimulated with the same frequency, the latency to reach the maximal effect was shortened. However, when two different frequencies were used instead, a response characterized by a combination of both phasic and tonic effect was obtained. In bilateral Ea with idential frequency but different onset time, the pressor effect elicited by the latter Ea showed no further increase during the stimulation period, however, when different frequencies were employed, each Ea elicited its own effect independently. The pressor effect elicited by Ea was abolished by regitine but not affected by adrenalectomy. It is concluded that a LFEa and a HFEa at Hoku with appropriate stimulation parameters can increase BP which is mainly due to potentiation of the sympathetic vasoconstrictor tone but via different central mechanisms.

Role of renal nerves on renal functional change after back heating in the rat.

This study was designed to investigate the possible role of renal nerves in the regulation of renal function after the application of heat (BH), by means of an electric heating pad (42 +/- 1 degree C) to the skin of the back overlying the kidneys. Both renal efferent (RENA) and renal afferent nervous activity (RANA) were recorded in 7 anesthetized female Wistar rats. It was found that RENA reduced to less than 80% of the control level during 30 min of back heating, accompanied by an increase in excretion of urine, sodium and potassium, and enhanced the glomerular filtration rate. BH in 9 chronic bilateral renal denervated rats (RD) showed the same renal responses as in the renal nerve intact rats (RI) after back heating. It is concluded that renal nerves played only a partially role in the renal diuretic action of back heating.

Low and high frequency electroacupuncture at Hoku elicits a distinct mechanism to activate sympathetic nervous system in anesthetized rats.

To address the effect of electroacupuncture (Ea) on autonomic nerve activity, the responses of rhythmic micturition contraction (RMC), urine excretion (UE), blood pressure (BP), renal sympathetic nerve activity (RNA) and pelvic parasympathetic nerve activity (PNA) to Ea were investigated in urethane-anesthetized rats. The acupoint Hoku (Li-4) was tested with two different stimulation frequencies (2 Hz and 20 Hz). Elongation of the RMC cycle and an increase in UE associated with the elevation of BP and RNA was elicited during Ea at Hoku. However, the pressor response induced by low frequency Ea (LFEa) was different from that by high frequency Ea (HFEa), i.e. a tonic effect was elicited by LFEa, while a phasic one was induced by HFEa. These results imply that: (1) Ea at Hoku may selectively activate the sympathetic, but not the parasympathetic nervous system, (2) Ea at Hoku with a different stimulation frequency may elicit a distinct mechanism to activate the sympathetic nervous system and (3) Ea at Hoku may ameliorate the hyperactive bladder in clinical therapy.

Differential clearance of nitroxide MRI contrast agents from rat cerebral ventricles.

Seven stable nitroxides have been evaluated as contrast agents in MRI studies of the rat cerebroventricular system. Because the contrast enhancement is primarily confined to the cerebral ventricles, nitroxides can be used to examine the ventricular structure. On the other hand, based on the absence of reducing agents in the rat CSF and on the fact that nitroxides can be reduced intracellularly, the relative reduction in contrast subsequent to an intracerebral injection provides information on the relationship of chemical structure to transmembrane flux in vivo. Observed rate constants and rate constants due to reduction have been analyzed quantitatively by modeling the effects of flow with GdDTPA, which is not subject to reduction. Five-membered ring nitroxides, in general, were reduced at much slower rates than six-membered ring nitroxides. The presence of a positive charge in the structure can substantially slow down the transmembrane flux.

Effect of subglottic pressure on fundamental frequency of the canine larynx with active muscle tensions.

The relation between subglottic pressure and the fundamental frequency of vocal fold vibration was studied by means of evoked phonation in an in vivo canine model. The evoked-phonation model involved electrical stimulation of the midbrain that resulted in consistent responses by respiratory and laryngeal musculature, accompanied by phonation. The dynamic stiffness properties of the vocal folds, especially the "cover," were investigated by delivering various amounts of air pressure to the larynx from an opening in the trachea. The fundamental frequency of vocal fold vibration increased linearly with subglottic pressure. The slopes ranged from 22.4 to 118.7 Hz per kilopascal in 7 animals. The results indicated that the dependence of fundamental frequency on subglottic pressure is a passive mechanical phenomenon.

An in vivo canine model for the study of phonation physiology by midbrain stimulation.

A versatile in vivo canine model is indispensable in studying the phonation function of the larynx. In this study, we attempted to build an in vivo phonation model in anesthetized dogs using stereotaxic electrical stimulation at a specific area in the midbrain. In each of the eight animals in this experiment, evoked phonation was successfully elicited by stimulating sites in the area ranging from 9 to 11 mm anterior, 3 to 5 mm lateral and 5 to 16 mm dorsal to the ear bar zero. This area was at the lateral border of the periaqueductal gray in the midbrain. The evoked-phonation process involved electrical stimulation of sites in this area, resulting in consistent responses by respiratory and laryngeal musculature accompanied by phonation. The evoked phonation could be consistently repeated. Different pitches of phonation were elicited by slightly moving the stimulation spots in this area. During evoked phonation, the subglottic aerodynamic power and individual laryngeal muscle action could be modified to study the effects of a single factor on the phonation process. The neuromuscular action for the control of phonation and the mechanical properties of the vocal folds can be investigated using an in vivo canine model.

Different central areas involved in the mechanisms of morphine antinociception in the mouse and the rat.

The antinociceptive effect of morphine quantitated by the tail-flick (TF) response was studied in mice and rats with various preparations, including: precollicular transection, partial and complete anemic decerebration, vertebral artery infusion, cross-circulation, spinal ligation, spinalization with dura mater intact and spinal subarachnoid infusion. In mice, either precollicular transection or partial anemic decerebration abolished or greatly reduced the morphine antinociceptive action (MAA). However, in rats, neither precollicular transection nor complete anemic decerebration caused any significant reduction in MAA. Studies of vertebral artery infusion and cross-circulation in both species indicated that opiate-sensitive antinociceptive receptors (OSAR) were present in the hindbrain. Although, spinal ligation eliminated MAA in both species, spinalization with dura mater intact only abolished the MAA in rats. On the other hand, studies of spinal subarachnoid infusion showed that only spinal antinociceptive neurons of mice were highly sensitive to the enzyme-resistant enkephalin (Enk) analog. From all these results suggested that both pre- and post-collicular structures are necessary for MAA in the mouse, however, in the rat only the post-collicular structures are essential, furthermore, the humoral pathway seems to play a more important role than the neural pathway in the inhibition of the TF response in the mouse but just the opposite in the rat. Therefore, it is concluded that the mechanisms of MAA are different between the mouse and the rat. The possible mechanisms of MAA in both species were discussed.

Involvement of alpha- and beta-adrenoceptors in antinociception at the lumber spinal level in mice.

To study the role of the adrenergic receptors in the regulation of nociceptive transmission in male albino mice, the antinociceptive activity of adrenergic drugs was tested with a tail-flick method. Subarachnoid infusion of phenylephrine and clonidine into T13-L1 of spinal cord produced a dose-dependent elevation of the nociceptive threshold in sodium pentobarbital anesthetized mice. The inhibitory effect of alpha-adrenoceptor agonists was antagonized by pretreatment with alpha-adrenoceptor antagonists. Isoproterenol also increased the nociceptive threshold significantly. The antinociceptive effect of isoproterenol was reversed by pretreatment with beta antagonist, propranolol. These findings suggest that spinal adrenergic receptors of both alpha and beta types probably are involved in the inhibition of nociceptive transmission.

Mechanisms of adrenaline-induced antinociception in mice.

Infusion of adrenaline into the upper lumbar subarachnoid space in lightly anesthetized mice produced a significant elevation of the nociceptive threshold as quantitated by tail flick test. The antinociceptive effect of adrenaline was dose-dependent and antagonized equally by pretreatment with either alpha-1 selective antagonist prazosin or alpha-2 selective antagonist yohimbine at a dose of 0.05 microgram/5 microliter/mouse. This antinociceptive effect of adrenaline was also blocked by pretreatment with beta antagonist propranolol or opiate antagonist naloxone at higher doses, i.e., 0.5 microgram and 1.0 microgram/5 microliter/mouse, respectively. These results suggest that the antinociceptive mechanisms of adrenaline at the lumbar spinal level in the mouse seem to be mediated not only through alpha- and beta-adrenergic pathways but also through opiate system.

Systemic vascular resistance is increased and associated with accelerated arterial stiffening change in patients with chronic cervical spinal cord injury.

BACKGROUND: Despite of stiffening change of conduit arteries, how total peripheral resistance (TPR) is adapted to chronic spinal cord injury (SCI) remains unclear. AIM: To investigate how chronic cervical SCI influences hemodynamic characteristics DESIGN: Cross-sectional, case-control study. SETTING: Rehabilitation department in the tertiary medical center. POPULATION: Twenty-one male patients with traumatic SCI resulting from cervical spine fracture were recruited. The injury occurred three to 289 months (46 months in average) previously. Twenty-one healthy male participants with matched age and body mass index were enrolled as control group. METHODS: The subjects were asked to maintain supine rest (SR) and then head-up tilt (HUT) at 60 degree for five minutes, respectively. A novel noninvasive bio-reactance device was employed to measure cardiac hemodynamics, whereas heart rate variability was used to determine cardiac autonomic activity. Additionally, the digital volume pulse analysis was applied to calculate arterial stiffness index (SI) and arteriolar reflection index (RI). RESULTS: SCI patients revealed less stroke volume and cardiac output (CO), as well as, greater total peripheral resistance (TPR) and SI during SR than normal subjects did. Moreover, the positive correlation between TPR and SI was observed in SCI patients rather than normal subjects. In SCI patients, HUT (1) markedly decreased TPR while CO and cardio-acceleration responses remained intact and (2) decreased HF power value but failed to change LF/HF ratio. Furthermore, the degree of orthostatic hypotension was correlated with the TPRHUT/TPRSR ratio but not the COHUT/COSR ratio. CONCLUSIONS: Chronic cervical SCI leads to a progressively accelerated increase in vascular stiffness, which is associated with increase in systemic vascular resistance. Furthermore, the cervical SCI-related orthostatic hypotension lies in the impairment of vasoconstriction without cardiac dysfunction. Clinical Rehabilitation Impact. SI, rather than blood pressure, reflects not only cardiovascular risk but also TPR in chronic cervical SCI.

Reciprocal inhibition during the tonic stretch reflex in the decerebrate cat.

1. The aim of this study was to investigate post-synaptic reciprocal Ia inhibition during the stretch reflex; particularly the extent to which an increased Ia excitation of the Ia inhibitory interneurones will be counteracted by recurrent inhibition from motor axon collaterals. For this purpose we investigated depression of monosynaptic test reflexes antagonist flexors (reciprocal inhibition) during static stretch of quadriceps or triceps surae in unanaesthetized decerebrate cats. 3. With increasing stretch of the extensor muscle there was first a linear augmentation of reciprocal inhibition, but along with the stretch reflex in the extensor a plateau appeared in the inhibition of the flexors, although the extensor stretch reflex (judged by the e.m.g.) increased with further stretching. Within the range of stretching of triceps surae which gave increased stretch reflexes the plateau in the reciprocal inhibition was usually maintained, while during stretching of quadriceps a second phase of augmenting reciprocal inhibition often appeared. Stretch beyond the level which increased the stretch reflex activity gave augmenting reciprocal inhibition both in case of quadriceps and triceps surae. 3. Excitability measurements from central terminals of Ia afferents revealed that the increasing reciprocal inhibition during increasing stretch reflex activity in quadriceps was associated with a primary afferent depolarization in knee flexor Ia afferents; there was no corresponding effect in ankle flexor Ia afferents during stretch reflexes in triceps surae. 4. The primary afferent depolarization evoked in knee flexor Ia afferents by electrical nerve stimulation was then compared with the presynaptic inhibition of knee flexor monosynaptic test reflexes produced by the same stimuli. The results suggest that the second phase of increasing reciprocal inhibition in knee flexors is due to presynaptic inhibition and accordingly that the depth of post-synaptic reciprocal inhibition remains constant at different degrees of stretch reflex activity in both knee and ankle extensors. 5. It is postulated that during increasing stretch reflex activity the increment in Ia excitation and recurrent inhibitio; on to the Ia inhibitory interneurones almost exactly balance each other. It is suggested that recurrent inhibition of Ia inhibitory interneurones may serve as a segmental autoregulatory mechanism to keep 'alpha-gamma-linked reciprocal inhibition' at a constant depth during different levels of agonist activity.