Noxious as well as hypertonic stimuli potentiate vasopressin and oxytocin secretion in rats. Neurohypophysial vasopressin- and oxytocin-secreting neurons receive inhibitory synaptic inputs mediated ...by γ-aminobutyric acid (GABA). Benzodiazepines modulate GABA-A receptor activity in a facilitatory fashion. It is thus possible that benzodiazepines suppress vasopressin and oxytocin release after noxious stimuli. To test this hypothesis, we investigated whether chlordiazepoxide impairs the enhanced release of vasopressin and oxytocin after noxious or hypertonic stimuli in male rats. Chlordiazepoxide (5–20 mg/kg, i.p.) blocked dose-dependently the vasopressin The results demonstrate that chlordiazepoxide selectively prevents vasopressin and oxytocin release after noxious stimuli and therefore suggest that the sites of chlordiazepoxide actions are not on the vasopressin or oxytocin neurons in rats.
The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious ...stimuli in the dorsal horn of the spinal cord (DH). The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol+progesterone increased the mean PPE mRNA content per cell by 100% compared with vehicle‐treated rats. Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol+progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P<0.02) but a strong trend towards a negative correlation coefficient after estradiol+progesterone treatment (P<0.06). ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P<0.01).
Noxious stimuli facilitate oxytocin release from the neurohypophysis. Oxytocin-secreting hypothalamic magnocellular neurosecretory neurons receive excitatory synaptic inputs from noradrenergic ...neurons in the medulla oblongata. The medulla oblongata includes the A2 noradrenergic and the Al noradrenergic cells. Here we investigated whether medullary noradrenergic neurons mediate oxytocin release after noxious stimuli in male rats. 5-Amino-2,4-dihydroxy-α-methylphenylethylamine, a neurotoxin selective for noradrenergic fibers, was injected into the lateral cerebral ventricle or the medulla. Seven days after the injection, the hypothalamic content of noradrenaline was decreased. In the rats injected with the neurotoxin, the release of oxytocin but not vasopressin after footshocks was impaired. Surgical ablation by suction of the caudal dorsomedial medulla including the A2 cell region did not significantly affect oxytocin release after footshocks, though the surgery abolished oxytocin release after i.v. injection of cholecystokinin octapeptide. In the: rats whose A2 cell region had been ablated, an i.c.v. injected al adrenoreceptor antagonist, benoxathian, blocked oxytocin release after footshocks. These results demonstrate that brainstem noradrenergic neurons mediate oxytocin release following noxious stimuli in the rat and suggest that responsible noradrenergic neurons are the Al cells in the caudal ventrolateral medulla.
Unilateral microinjection of carbachol (1 microgram) into the dorsal parabrachial region (PBR) of conscious guinea pigs produced a 100% increase in the duration of restraint-induced tonic immobility ...(TI) episodes. In another group of animals with a subcutaneous electrode introduced into the thigh region, microinjections of equivalent doses of the same drug in similar sites also significantly reduced the motor defense and vocalization responses elicited by the application of a noxious electrical stimulus to the skin. Both effects were blocked by pretreatment with atropine. The possible simultaneous activation of mechanisms modulating TI and the response to a noxious stimulus may be of adaptive importance since analgesia may reinforce immobility to permit the use of other defense mechanisms in a situation of prey/predator confrontation.
We compared the effects of intrathecal administration of antiserum against calcitonin gene-related peptide (CGRP) between thermo- and mechano-nociceptive responses, using experimental hyperalgesic ...rats. An intrathecal administration of anti-CGRP antiserum, but not antiserum absorbed by synthetic CGRP, normalized either adjuvant- or carrageenin-induced hyperalgesia both in the paw radiant heat and the paw pressure tests, with little effect on non-hyperalgesic paws. These results suggest that endogenous CGRP, probably present in primary afferents, promotes both thermo- and mechano-nociceptive transmission in the spinal dorsal horn, at least in the hyperalgesic states with inflammations.
In an on-going study on mechanisms by which activation of sensory afferents regulates nociception, high-intensity, low-frequency electrical stimulation was applied to previously defined meridian and ...non-meridian points of the hindlimb or forelimb, and the effects measured on the withdrawal reflex of the tail or limb in the lightly anesthetized rat. Withdrawal was evoked by application of noxious radiant heat to the tip of the tail or to the plantar surface of a hindpaw or forepaw. Parameters of conditioning electrical stimulation were 2 ms pulses at 4 Hz for 20 min at 20 × threshold (20–30 mA) where threshold was the minimum intensity which evoked muscle twitch. In experiments on tail withdrawal, stimulation applied to meridian points
fengshi (GB-31),
femur-futu (ST-32) and
zusanli (ST-36) of the hindlimb or to
wai-kuan (TH-5) and
hoku (LI-4) of the forelimb increased the latency of the withdrawal reflex to 70–100% of the maximum possible inhibition (MPI) during the stimulation. Inhibition persisted for more than 1 h after the end of stimulation. Bilateral stimulation of hindlimb meridian points evoked a greater inhibition during the stimulation ( > 95% of the MPI); the inhibition persisted for 40 min. Stimulation of non-meridian sites in hindlimb or forelimb inhibited the withdrawal reflexes by 45–50% of the MPI during the stimulation only. Thus, the evoked inhibition has two components, a brief effect elicited by non-meridian point stimulation and a persistent post-stimulation effect produced only upon stimulation of meridian points. Stimulation produced little effect on nociceptive limb withdrawal reflexes. The results suggest that high-intensity, low-frequency electrical stimulation of meridian points produced a long-lasting, extrasegmental inhibition of the tail withdrawal but not of limb withdrawal reflexes. This differential inhibition may be due to differences in neuronal circuitry and CNS modulatory control mechanisms. The persistent inhibition appears to be dependent on the site of stimulation because it is not evoked by stimulation of sites outside of meridian points.
Skin perfusion was measured using laser Doppler fluximetry (LDF) in 16 preterm babies undergoing a standardised heel prick procedure. Although there was a significant reduction in skin blood flow ...following the heel prick, this was variable and dependent on basal skin blood flow. This, together with loss of data due to movement artefact, makes this technique unreliable in quantifying the sympathetic response to a noxious stimulus in preterm infants.
The aim of these experiments was to examine the changes in antinociception elicited by morphine or glutamate stimulation of the periaqueductal gray of the midbrain (PAG) during the postnatal ...development of the rat. Pups, aged 3, 10, and 14 days, were implanted with cannulas aimed at either the dorsal or the ventral aspect of the PAG, and glutamate (vehicle, 60 mM or 180 mM) or morphine (vehicle, 2 micrograms or 6 micrograms) was microinjected into one of those two sites. Pups were tested for analgesia against noxious thermal and mechanical stimuli. Morphine produced analgesia at 3 and 10 days of age only when administered to the ventral part of the PAG and the thermal noxious stimulus was tested. Conversely, analgesia induced by glutamate was seen at 3 and 10 days of age only when glutamate was given to the dorsal aspect of the PAG and the mechanical stimulus was used. In 14-day-old pups, both drugs produced analgesia against both types of noxious stimuli regardless of their site of administration within the PAG. Systemically administered naloxone attenuated the analgesic effects of both drugs when they were administered to the ventral PAG, but did not consistently attenuate the analgesic effect of either compound given to the dorsal aspect of the PAG. When either morphine or glutamate was injected into the ventral PAG, intrathecal injections of methysergide attenuated analgesia against the thermal stimulus to a significantly greater degree than the mechanical stimulus and intraspinal injection of phentolamine attenuated analgesia against the mechanical stimulus more potently. When glutamate was given to the dorsal PAG, analgesia against both stimulus types was significantly attenuated. These results indicate that the morphine- and glutamate-induced analgesia mediated by the PAG are developmentally differentiated. These ontogenetic differences most likely reflect differences in the mechanism of action by which these drugs produce analgesia when administered to the PAG, as well as neuroanatomical differences within the dorsal and the ventral regions of the PAG.
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