The dorsal raphe nucleus: a re-evaluation of its proposed role in opiate analgesia systems.

Previous studies have concluded that (a) electrical stimulation in the periaqueductal gray/dorsal raphe nucleus (PAG/DRN) region specifically produces either non-opiate or opiate forms of antinociception dependent upon the dorsoventral level of stimulation and (b) the 'opiate' form of stimulation-produced analgesia (SPA) arising from the ventral PAG/DRN region shows cross-tolerance with opiate forms of footshock analgesia, implying common neural substrates. This latter conclusion in turn implies that SPA elicited from the ventral PAG/DRN region would be expected to be antagonized by scopolamine, since this muscarinic cholinergic antagonist blocks opiate footshock analgesia. The present study demonstrates instead that neither 10 mg/kg naloxone nor 10 mg/kg scopolamine had any effect on SPA elicited from sites histologically verified to lie within the presumptive 'opiate' ventral PAG/DRN region. These data bring into question both the site specificity of opiate SPA and the common mediation of ventral PAG/DRN SPA and opiate forms of footshock analgesia.

Electrical stimulation of the rat ventral midbrain elicits antinociception via the dorsolateral funiculus.

The pain-suppressive effects of focal electrical stimulation of sites throughout the ventral midbrain were examined in awake rats. Chronic bipolar electrodes were implanted in medial and lateral regions of the midbrain. Current thresholds for suppression of the tail-flick reflex in response to noxious heat were determined for both a biphasic and a monophasic stimulation parameter at each site. Stimulation of areas throughout the ventral midbrain produced tail-flick suppression (TFS), but no one area was consistently effective in all animals. Monophasic and biphasic stimulation were qualitatively equal in the duration of TFS and the distribution of effective sites. The production of TFS was not correlated with other behavioral reactions to brain stimulation. TFS appeared to be mediated by non-opiate pathways since naloxone administration (10 mg/kg) had no discernible effect on the production of TFS. The current threshold for producing TFS was extremely variable over both short (one half hour) and long (one week) intervals. The incidence of TFS from previously effective sites was significantly less following bilateral dorsolateral funiculus (DLF) lesions, indicating that the antinociceptive effects of ventral midbrain stimulation are mediated by this spinal pathway.

Naloxone does not consistently affect inhibition of spinal nociceptive transmission produced by medial diencephalic stimulation in the cat.

In cats anesthetized with sodium pentobarbital and artificially ventilated with 70% N2O, the response of single lumbar dorsal horn units to noxious radiant heat stimuli (50 degrees C, 10 sec) applied to glabrous footpad skin were recorded with microelectrodes. Unit heat-evoked responses were markedly suppressed by electrical stimulation (100 msec pulse trains at 100 Hz, 3/sec, 50-300 microA) at sites in the medial basal diencephalic periventricular gray, lateral hypothalamic area, preoptic area, and posterior basal telencephalon. Inhibition of dorsal horn unit responses produced by brain stimulation was not consistently affected following systemic administration of the opiate antagonist naloxone (0.5-1 mg/kg i.v.), indicating that the endogenous opioid peptides are not primarily involved in the mediation of this descending inhibition under the experimental conditions.

Brood patch innervation and its role in the onset of incubation in the turkey hen.

The source of innervation to the brood patch in turkey hens was determined by recording the electrophysiological activity of cutaneous nerves while manually stimulating various regions of the skin. The entire area of the brood patch was innervated by eight nerves, arising from thoracic vertebra 3 to synsacrothoracic vertebra 1. To determine whether afferent input from the brood patch influenced egg production or incubation behavior, hens were bilaterally denervated prior to photoinduced egg production. Denervated hens visited nests the same number of times, but stayed on the nest for less total time than controls by the fourth week of photostimulation. Serum prolactin levels rose in control hens but not in denervated hens. Egg production was maintained in the denervated hens but not in controls. None of the denervated hens displayed incubation behavior. This experiment supports the view that peripheral nervous input plays a role in the onset of incubation behavior.

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation.

Responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25-600 microA) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42-43 degrees C) to 52 degrees C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5 degrees and 1 degree C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by greater than 25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.

Serotonin involvement in descending inhibition of spinal nociceptive transmission produced by stimulation of medial diencephalon and basal forebrain.

The responses of single lumbar dorsal horn neurons to noxious radiant heat stimuli (50 degrees C, 10 sec) applied to glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. Responses were markedly reduced during electrical stimulation (100-msec trains at 100 Hz, 3/sec, up to 400 microA) at sites in the medial diencephalic periventricular gray (PVG), preoptic area, and basal forebrain. A role for serotonin (5-hydroxytryptamine, 5-HT) was investigated by determining whether descending inhibition from these areas could be affected by (1) acute systemic administration of the 5-HT antagonist methysergide, or (2) depletion of central 5-HT levels by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 500 mg/kg, i.p.). Inhibition produced by stimulation at these sites was reduced or abolished in 22 cases following administration of methysergide (0.2 to 1 mg/kg) to non-pretreated cats. In the PCPA-pretreated cats, stimulation in preoptic or basal forebrain areas inhibited the responses of 26 units to noxious skin heating to varying degrees; PVG stimulation inhibited the responses of 14 of 26 units, while the remainder were unaffected. The mean current threshold for inhibition produced by PVG or preoptic/basal forebrain stimulation was significantly higher, while mean inhibition at 200 microA was significantly lower, in units from PCPA-pretreated cats compared to those from non-pretreated cats. The results indicate that 5-HT may be involved in the mediation of spinal inhibition produced by medial diencephalic and basal forebrain stimulation.

Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by medial preoptic and septal stimulation in the cat.

1. Responses of single lumbar dorsal horn units to controlled noxious radiant heating of glabrous hindfoot skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. The heat-evoked responses of all units studied were markedly suppressed during concomitant electrical stimulation (mean, 30 Hz; 25-300 microA) of medial preoptic and ventromedial septal areas. 2. Brain sites at which stimulation inhibited spinal neuronal heat-evoked responses were mapped by systematically varying the depth of the stimulating electrode in tracks at anteroposterior levels +14 through +18. At each stimulation site, the magnitude of the spinal neuronal response to heat (50 degrees C, 10 s, 1 per 3 min) during brain stimulation was expressed as a percentage of the control response (no brain stimulation), which was stable in size over repeated trials. Sites at which stimulation markedly reduced the heat-evoked response were located in the medial preoptic area and in the ventromedial septum (diagonal band of Broca) up to anterior level +17. 3. The magnitude of inhibition increased with graded increases in brain-stimulation intensity. For 15 units, the mean current threshold to generate inhibition was 25 microA. 4. Responses of dorsal horn neurons to a series of graded noxious heat stimuli increased linearly from threshold (40-45 degrees C) to 52 degrees C. The slopes of such linear temperature-response curves were significantly reduced, without a change in the response threshold, when the temperature series was repeated during concomitant preoptic or septal stimulation. 5. The possible relationship of the medial preoptic and septal areas to inhibitory systems in the brain stem, and their possible role in analgesic mechanisms, are discussed.

Effects of hyperdynamic fields on input-output relationships and long-term potentiation in the rat hippocampus.

The effects of a 2G force environment on synaptic plasticity were examined in the rat hippocampus. Field potentials from neurons in the CA1 pyramidal cell layer were evoked by stimulation of the afferent Schaffer collateral/commissural fibers in an in vitro slice preparation. Input-output (I-O) relationships of the circuit were determined before and after tetanizing stimuli given to induce long term potentiation (LTP), a form of neural plasticity. I-O curves from animals exposed to 2G via centrifugation for either 2 or 14 days were not different from those obtained in control (1G) animals. Similarly, induction of LTP was equivalent in all groups, showing increases in maximum amplitude, slope and midpoint response of the fitted Boltzmann functions compared to un-tetanized controls. Comparison of slices from dorsal and ventral hippocampus showed the location of the slice had no effect of LTP expression. We conclude that, in contrast to other reports of functional changes in the central nervous system under altered force environments, cellular mechanisms of synaptic plasticity, which may underlie learning and memory, are preserved in the hippocampus.

Binocular dissecting microscopic studies on the density of toruli tactile in the La Mancha goat.

The Merkel cells and associated nervous terminal plates have been called toruli tactiles (TT). These structures can be ubiquitously seen on the shaved hairy skin after staining with a methylene blue solution. Four La Mancha goats of both sexes were examined for the density of TT. TT were visually located under a binocular dissecting microscopic (14x) and then the number of TT in the field was directly counted. The density of TT in different corporal areas of the body surface was estimated from the mean of several two-cm square samples of skin. The results obtained are as follows: The mean number per two-cm square on the whole body surface ranged from 10.06-11.36 in the male specimen and from 12.98-14.32 in the female specimen. The density of TT was rather high in the temporal and buccal areas, on the neck, chin and cranial breast, and on the lateral surface of the arm, thigh and leg. Density was moderate in the fronto-parieto-occipital area (female), on the loin and buttocks, in the upper costal, lower caudo-costal, xiphoid-umbilical and umbilical-pubic areas, and on the lateral surface of the forearm. TT were absent or very few in number on the nose and chin, the scrotum, caudal-pubic area of males, the udder, the vulva, and the digitorum manus et pedis.

Sleep deprivation impairs long-term potentiation in rat hippocampal slices.

To determine if 12-h sleep deprivation disrupts neural plasticity, we compared long-term potentiation (LTP) in five sleep-deprived and five control rats. Thirty minutes after tetanus population spike amplitude increased 101 +/- 15% in 16 slices from sleep deprived rats and 139 +/- 14% in 14 slices from control rats. This significant (P < 0.05) reduction of LTP, the first demonstration that the sleep deprivation protocol impairs plasticity in adult rats, may be due to several factors. Reduced LTP may indicate that sleep provides a period of recuperation for cellular processes underlying neural plasticity. Alternatively, the stress of sleep deprivation, as indicated by elevated blood corticosterone levels, or other non-sleep-specific factors of deprivation may contribute to the LTP reduction.

Dorsal nerve root origins of the cutaneous nerves of the feline pelvic limb.

The dorsal root origins of cutaneous nerves supplying the feline pelvic limb were determined electrophysiologically in 11 cats. Cutaneous nerves were surgically exposed and the presence or absence of an evoked potential in response to stimulation of individual dorsal roots was noted. The dorsal cutaneous branches of L3-L5 and S3, and the lateral cutaneous branch of L3 each arose solely from their parent spinal nerves. The L7, S1, and S2 dorsal cutaneous branches had multiple dorsal root origins. The lateral cutaneous femoral nerve originated from L3-L6 dorsal roots in 4 patterns of origin, and the saphenous nerve originated from L4-L6 dorsal roots in 2 patterns of origin. The lateral and caudal cutaneous sural nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The lateral and medial plantar nerves arose from L6-S2 roots in 4 and 2 patterns, respectively. The superficial and deep peroneal nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The caudal cutaneous femoral nerve or its branches arose from L7-S3 in 8 origin patterns. The dorsal nerve of the penis and the superficial perineal nerve arose from L7-S3 and S1-S3 roots, respectively, each in 4 patterns. A subtle correlation between plexus type and dorsal root origins of the cutaneous nerves was noted.