The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide

The effect of capsaicin-induced stimulation of afferent neurons on peristalsis and the possible neural mediators involved in this action were examined in the guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. Capsaicin (0.1–1 M) caused an initial short-lasting stimulation of peristalsis followed by a prolonged inhibition of peristaltic activity. Capsaicin (1 M) was ineffective when the gut segments had been pretreated with 3.3 M capsaicin, which is indicative of an afferent neuron-dependent action of the drug. In contrast, the abolition of peristalsis caused by a high concentration of capsaicin (33 M) was fully reversible on removal and reproducible on readministration of capsaicin, a feature characteristic of a nonspecific depression of smooth muscle excitability. Baseline peristalsis and the excitatory/inhibitory effect of capsaicin (1 M) on peristalsis remained unaltered by a combination of the tachykinin NK₁ receptor antagonist ( + )-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 M) and the tachykinin NK₂ receptor antagonist L(-)-N-methyl-N[4-acetylamino-4-phenyl-piperidino-2-(3,4-dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 M). Further experiments, performed in the presence of a low concentration of atropine (10 nM) showed that the catcitonin gene-related peptide (CGRP) antagonist human -catcitonin gene-related peptide (8–37) [hCGRP (8–37); 10 M] attenuated the delayed inhibitory effect of capsaicin on peristalsis, but did not influence baseline peristaltic activity and the capsaicin-induced facilitation of peristalsis. Blockade of nitric oxide (NO) synthesis by N ^G-nitro-l-arginine methylester (l-NAME, 300 M) facilitated baseline peristaltic activity and reduced the delayed inhibition of peristalsis caused by capsaicin (1 M) without affecting the initial peristalsis-stimulating action of capsaicin. The effects of l-NAME were prevented by l-arginine (1 mM). The data of the current study indicate that capsaicin-sensitive afferent neurons do not participate in the neural pathways subserving peristalsis in the guinea-pig small intestine, but modulate peristaltic activity upon stimulation with capsaicin. The initial stimulant action of capsaicin on peristalsis is independent of tachykinins acting via NK₁ or NK₂ receptors, while the delayed capsaicin-induced depression of peristalsis involves CGRP and NO.     

The influence of experimental muscle pain on the human soleus stretch reflex during sitting and walking.

OBJECTIVES: The stretch reflex is functionally important during human locomotion. Muscle pain has been found to increase the stretch reflex amplitude during sitting, possibly due to an altered fusimotor drive. To further study the importance of altered fusimotor activity due to muscle pain we investigated the combined effect of muscle pain and motor task on the soleus stretch reflex. METHODS: Stretch reflexes were elicited before, during and after experimentally induced muscle pain in soleus (i.m. infusion of 6% saline) in 3 experiments: (1) in the relaxed soleus muscle and before, during and after an isometric ramp contraction (500 ms, 0-10 Nm), (2) at 3 different time periods during walking, and (3) at matched pain intensity and soleus activity during sitting and walking. RESULTS: Infusion of hypertonic saline into the soleus muscle caused a significant facilitated stretch reflex in the relaxed muscle (P<0.01), but not during walking or during sitting and walking at matched soleus EMG and matched pain levels. The infusion of isotonic saline (non-painful) did not cause any changes (P = 0.75). CONCLUSIONS: The main findings of the present study were that experimental muscle pain facilitated the stretch reflex during pain in the relaxed muscle, but caused no changes in stretch reflex amplitude during sitting and walking at higher "functional" background EMG levels.     

Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor

Modulation of the sexual behavior of male rats by the anxiolytic buspirone (S-20499) and its analog gepirone were compared to the effects of 8-OH-DPAT (or DPAT, a selective 5-HT1A reference agonist), and BMY-7378 (a selective 5-HT1A partial agonist). Long-Evans rats were used; modulation of copulatory behavior and alteration of penile reflexes were examined. Modulation of copulatory behavior was assessed by three indices: frequency and length of intromission, and latency of ejaculation. DPAT, at doses of 1-8 mg/kg, reduced these three indices in a time dependent manner such that the effects peaked at 45 min and normalized at 90 min. The dose-effect relationship (assessed 45 min after DPAT injection) is bell-shaped with an ED50 approximately 1 mg/kg on the ascending limb of the curve. The effects of buspirone (2 mg/kg) and gepirone (2 mg/kg) on copulatory behavior were indistinguishable from control. BMY-7378 alone and in combination with these other 5-HT1A agonists reduced copulatory behavior, though not statistically significant. Penile reflexes, including number of erections, cups and flips, were inhibited by these agents: DPAT>buspirone>gepirone (inactive at 2 mg/kg). Furthermore, the latency period to erection was at least doubled by DPAT (2 mg/kg). Buspirone and gepirone, however, reduced the latency period to erection. BMY-7378 inhibited penile reflexes when administered alone and even more in combination with DPAT or buspirone. Two butyrophenone analogs, spiperone (a 5-HT1A and dopamine D2 antagonist) and haloperidol (a D2 antagonist), were also tested for their interaction with DPAT. Both of these drugs (at 0.25 mg/kg, 60 min after administration) reduced all indices of penile reflexes and copulation. Furthermore, in combination with DPAT (2 mg/kg, 45 min), the effects were synergistic such that sexual activity came nearly to a standstill. These opposing effects on putatively brain originated copulatory behavior and spinal mediated penile reflexes indicate that the effects of buspirone and DPAT on sexual behavior in the male rat may be possible at different parts of the central nervous system. If a tentative shared target site by DPAT and buspirone is the 5-HT1A receptor, than the same 5-HT receptor sub-type at different locations (brain, raphe nuclei, spinal cord and autonomic ganglia) may modulate rat sexual behavior in opposing ways.     

Withdrawal from oral cocaine in rats: ultrasonic vocalizations and tactile startle

While anxiety appears to characterize humans who administer high doses of cocaine or experience withdrawal from cocaine, it is difficult to capture this aspect of cocaine effects in animals. The present study investigated if acute or protracted withdrawal from prolonged low-dose cocaine that is self-administered via the oral route could be detected in tactile startle and vocal distress responses of rats. Adult, male Long-Evans rats had access to cocaine solution (0.1 mg/ml) either for 24 or 4 h/day using the two-bottle choice technique. The amount of solution consumed from each bottle was measured daily for 30 or 60 days. On days 1, 3, 7, 14, 21, 28 of withdrawal, startle and ultrasonic vocal responses (USV, 15–35 kHz) were measured in response to 18 airpuff stimuli (20 psi). Rats drank an average of 5–20 mg/kg per day of the cocaine solution. On average, about half of the daily liquid was consumed from the cocaine solution-containing bottle. USVs were emitted at significantly increased rates on day 3 of withdrawal from 30 or 60 days of cocaine drinking. Startle reactions were slightly, but non-significantly increased on day 1 of withdrawal. Comparable to withdrawal from ethanol, morphine, and diazepam treatments, withdrawal from oral self-administration of low to moderate doses of cocaine increases the rate of ultrasonic vocalizations while increasing minimally the amplitude of startle responses to low-intensity tactile stimuli. Nevertheless, no correlation between the total amount of cocaine self-administered or the duration of treatment with the intensity of the withdrawal manifestations could be detected.     

Importance of the Locus coeruleus and involvement of α-adrenergic receptors in the post-decapitation reflex in the rat

The latency, duration, hindlimb kick frequency, and total activity components of the post-decapitation reflex (PDR) were measured in the rat using a movement-sensitive transducer. Reduction of brain and spinal cord norepinephrine (NE) caused by neonatal administration of 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine, which also reduced brain serotonin, decreased all components of the PDR. Depletion of serotonin or dopamine alone reduced the vigor of the reflex, suggesting that these pathways can influence the PDR but are not essential for the response. Lesions of neurons in the Locus coeruleus, made electrolytically or with 6-OHDA, decreased the intensity of the PDR, with the 6-OHDA-induced lesion being more effective. Depletion of forebrain NE terminals with 6-OHDA did not alter the PDR, consistent with a critical involvement of spinal noradrenergic fibers. The PDR was also decreased by phentolamine and prazosin, but not by propanolol, suggesting an involvement of -adrenergic receptors in the response. This hypothesis was further supported by the finding that the efficacy of a variety of drugs (such as tricyclic antidepressants, phenothiazines, and antihypertensive compounds) for blocking the reflex was apparently related to their affinity for -adrenergic receptors. Thus, the PDR is dependent on noradrenergic fibers in the spinal cord and may provide a simple screen for drugs with suspected -adrenergic blocking properties or for agents that disrupt the function of central noradrenergic fibers.Bruce A. Pappas was a visiting Professor on sabbatical leave from the Department of Psychology, Carleton University, Ottawa, Canada K1S 5B6     

Intrathecal substance P depresses the tail-flick response — Antagonism by naloxone

Summary Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 g to 100 g per rat (ED 50: 1.5 g/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 g to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 g/rat) or i.p. (0.5 mg/kg) injections of naloxone.Supported by the Sonderforschungsbereich 38 Membranforschung     

Autonomic nervous system function in myotonic dystrophy

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.

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Sommario Nei pazienti affetti da Distrofia Miotonica si riscontrano spesso sintomi che suggeriscono un'alterata funzione del Sistema Nervoso Vegetativo. Abbiamo sottoposto a valutazione dei riflessi cardiovascolari e dei livelli ematici di catecolamine (adrenalina e noradrenalina) in condizioni basali, in psizione supina e dopo lo stimolo ortostatico e cold-pressor 12 pazienti affetti da Distrofia Miotonica. L'analisi statistica dei dati non ha mostrato differenze fra i pazienti e un gruppo di controllo comparabile per sesso ed età.

     

Adult Retinofugal Axons Regenerating Through Peripheral Nerve Grafts Can Restore the Light-induced Pupilloconstriction Reflex

To investigate the ability of mature regenerating retinal axons to form functional connections within central targets, severed axons were guided into the primary visual centres which subserve the pupillary constriction reflex in response to light. The ocular stump of the transected optic nerve of adult rats was connected by means of an autologous peripheral nerve graft with the pretectal region which contains the relay nucleus of pupillary constriction, the olivary pretectal nucleus. This nucleus is efferently connected with preganglionic neurons in the oculomotor nuclear complex which innervates parasympathetically the muscle constrictors of the iris. Six to sixteen weeks after optic nerve transection and peripheral nerve transplantation, brisk responses were observed in the pupils upon illumination of the transplanted eye. Recovery of the pupil responses indicated that retinal neurons used the peripheral nerve 'bridge' to access the pretectum, in which they established synaptic contacts in sufficient density and with appropriate specificity to reconstitute the function of the traumatically interrupted neuronal circuitry.     

Effects of intravenously administered lidocaine on pulmonary vagal afferents and phrenic nerve activity in cats

The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1mg·kg^–1 or 2mg·kg^–1) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor).(Aoki M, Harada Y, Namiki A, et al.: Effects of intravenously administered lidocaine of pulmonary vagal afferents and phrenic nerve activity in cats. J Anesth 6: 395–400, 1992)     

针灸治疗胆汁返流性胃炎近况

系统回顾及总结了近几年来有关针灸治疗胆汁返流性胃炎(BRG)的文献，认为针灸防治BRG具有肯定的临床疗效和优势，并为进一步探索提供思路。