Halothane sensitizes cutaneous nociceptors in monkeys

1984 ◽  
Vol 52 (4) ◽  
pp. 762-770 ◽  
Author(s):  
J. N. Campbell ◽  
S. N. Raja ◽  
R. A. Meyer

The effects of halothane on the responses of C-fiber (CMHs) and A-fiber (AMHs) nociceptive afferents sensitive to mechanical and heat stimuli were studied in monkeys. The response to heat stimuli was studied with use of a laser thermal stimulator that provided stepped increases in skin temperature over a 7.5-mm-diameter area with rise times to the desired temperature near 100 ms. Recordings were obtained from single fibers that innervated the glabrous skin of the hand using a teased-fiber dissection technique. In initial studies the response of 32 CMHs and 45 AMHs in monkeys anesthetized with pentobarbital sodium (3-6 mg X kg-1 X h-1) was compared with the response of 12 CMHs and 23 AMHs in monkeys anesthetized with a combination of halothane (0.8%) and N2O (67%). A standardized set of 10 3-s heat stimuli ranging from 41 to 49 degrees C delivered every 30 s were applied to the receptive field. Both AMHs and CMHs had a lower threshold and greater response to suprathreshold heat stimuli under conditions of halothane-N2O anesthesia. The threshold to mechanical stimuli, as tested by von Frey hairs, was not significantly different. Five CMHs and 5 AMHs were studied in a crossover study in which responses to the 41-49 degrees C stimuli were obtained first under halothane-N2O (0.8%-67%) anesthesia, then under an ultrashort acting barbiturate, methohexital (2-9 mg/kg over 15 min), and finally once again under halothane-N2O anesthesia. For the five CMHs, the mean cumulative response was 1.8 times greater, whereas for the five AMHs the response was 4.7 times greater under halothane as opposed to barbiturate anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

1990 ◽  
Vol 64 (5) ◽  
pp. 1502-1513 ◽  
Author(s):  
R. D. Treede ◽  
R. A. Meyer ◽  
J. N. Campbell

1. Receptive-field properties were investigated in cutaneous C-fiber nociceptive afferents (CMH) responsive to mechanical and heat stimuli. Teased-fiber techniques were used to record from 28 CMHs that innervated the hairy skin of upper or lower limb in anesthetized monkeys. 2. The response to mechanical stimuli was studied with the use of calibrated von Frey probes. The response to heat stimuli was studied with the use of a laser thermal stimulator that provided stepped increases in skin temperature with rise times to the desired temperature near 100 ms. The size of the receptive field (RF) for mechanical stimuli was determined by use of a suprathreshold stimulus that consisted of a 0.5-mm-diam probe that exerted a 200-mN force (10 bar). The size of the heat RF was determined by use of a 49 degrees C stimulus applied to a 7.5-mm-diam area for 1 s. 3. Heat thresholds were determined with an ascending series of stimulus intensities and were found to be stable over many hours: they ranged from 37 to 46 degrees C (mean, 41.1 degrees C). Mechanical thresholds ranged from 1.3 to 7.3 bar (mean, 3.3 bar). There was no correlation between mechanical and heat thresholds. Both thresholds extended well below the corresponding psychophysical pain thresholds in the literature. This suggests that spatial and/or temporal summation of C-fiber input are important for pain induced by either stimulus modality. 4. Mechanical RF diameters ranged from 3.3 to 9.6 mm (mean, 4.7 mm); heat RF diameters ranged from punctate (less than 1 mm) to 9.5 mm (mean, 4.3 mm). There was a significant linear correlation between mechanical and heat RF sizes with a slope of one. The distance between the center of the mechanical RF and the center of the heat RF along one axis ranged from 0 to 1.1 mm (mean, 0.4 mm). These data indicate that the heat RFs coincided with the mechanical RFs. 5. Within the mechanical RF determined with the suprathreshold stimuli, all CMHs had one or more punctate areas of maximal mechanical sensitivity where mechanical threshold was lowest. Heat excitability extended greater than 2 mm beyond these mechanically sensitive spots. Because lateral transmission of the heat stimulus is small, this indicates that heat transduction occurs outside the regions of maximal mechanical sensitivity. 6. Both the threshold to heat and the response magnitude at suprathreshold intensities depended on the percentage of the RF area overlapped by the heat stimulus. This indicates that multiple transducer sites probably contribute to the total evoked response.(ABSTRACT TRUNCATED AT 400 WORDS)


1995 ◽  
Vol 73 (4) ◽  
pp. 1721-1723 ◽  
Author(s):  
D. F. Bossut ◽  
E. R. Perl

1. The effects of sympathetic stimulation and close arterial injection of norepinephrine were tested on cutaneous myelinated-fiber (A delta) mechanical nociceptors [high-threshold mechanoreceptors-(MyHTMs)] from normal and from partially transsected nerves. 2. Neither sympathetic stimulation nor close arterial injection of norepinephrine (200 ng) excited MyHTMs (18) recorded from the uninjured great auricular nerve of adult rabbits. 3. MyHTMs (58) conducting across the site of partial cut lesions, made 2 to 28 days previously, had threshold and responsiveness to mechanical stimuli, receptive field organization, and absence of background discharge typical of such elements in normal nerve. 4. Four MyHTMs recorded from the injured nerves were excited by sympathetic stimulation and/or norepinephrine injection but only one gave more than two impulses within 60 s to either form of stimulation. 5. The meagerness of the sympathetic and adrenergic excitation of MyHTMs after nerve injury contrasts with that observed under similar conditions for C-fiber polymodal nociceptors. Therefore, induction of adrenergic responsiveness in nociceptors after partial denervation in cutaneous MyHTMs appears to be less important for mechanisms related to pathogenic pain than alterations in certain C-fiber nociceptors.


1993 ◽  
Vol 69 (4) ◽  
pp. 1071-1081 ◽  
Author(s):  
K. D. Davis ◽  
R. A. Meyer ◽  
J. N. Campbell

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.


1990 ◽  
Vol 63 (3) ◽  
pp. 473-490 ◽  
Author(s):  
J. F. Bernard ◽  
J. M. Besson

1. Neurons were recorded in the parabrachial (PB) area, located in the dorsolateral region of the pons (with the use of extracellular micropipette), in the anesthetized rat. Parabrachioamygdaloid (PA) neurons (n = 67) were antidromically identified after stimulation in the centralis nucleus of the amygdala (Ce). The axons of these neurons exhibit a very slow conduction velocity, between 0.26 and 1.1 m/s, i.e., in the unmyelinated range. 2. These PA neurons were located in a restricted region of the PB area: the subnuclei external lateral (PBel) and external medial (PBem). A relative somatotopic organization was found in this region. 3. These units were separated into two groups: 1) a group of nociceptive-specific (NS) neurons (69%), which responded exclusively to noxious stimuli, and 2) a group of nonresponsive (NR) neurons (31%). 4. The NS neurons exhibited low or lacked spontaneous activity. They responded exclusively to mechanical (pinch or squeeze) and/or thermal (waterbath or waterjet greater than 44 degrees C) noxious stimuli with a marked and sustained activation with a rapid onset and generally without afterdischarge. Noxious thermal stimuli generally induced a stronger response than the noxious mechanical stimuli. These neurons exhibited a clear capacity to encode thermal stimuli in the noxious range: 1) the stimulus-response function was always positive and monotonic; 2) the slope of the curve progressively increased up to a maximum where it was very steep, then the steepness of the slope decreased close to the maximum response; and 3) the mean threshold was 44.1 +/- 2 degrees C, and the point of steepest slope of the mean curve was around 47 degrees C. 5. The excitatory receptive fields of the NS neurons were large in the majority (70%) of the cases and included several areas of the body. A more marked activation was often obtained from stimuli applied to one part of the body, denoted as the preferential receptive field (PRF). In the other cases (30%), the excitatory receptive field was relatively small (SRF) and restricted to one part of the body (the tail, a paw, a hemiface, or the tongue). Both the PRF and SRF were more often located on the contralateral side. In addition, noxious stimuli applied outside the excitatory receptive field were found to strongly inhibit the responses of NS neurons. 6. All the NS neurons responded to intense transcutaneous electrical stimulation applied to the PRF or SRF with two peaks of activation.(ABSTRACT TRUNCATED AT 400 WORDS)


2012 ◽  
Vol 71 (suppl_1) ◽  
pp. ons160-ons172 ◽  
Author(s):  
Richard Gonzalo Párraga ◽  
Guilherme Carvalhal Ribas ◽  
Leonardo Christiaan Welling ◽  
Raphael Vicente Alves ◽  
Evandro de Oliveira

Abstract BACKGROUND: The fiber dissection technique provides unique 3-dimensional anatomic knowledge of the white matter. OBJECTIVE: To examine the optic radiation anatomy and its important relationship with the temporal stem and to discuss its findings in relation to the approaches to temporal lobe lesions. METHODS: We studied 40 cerebral hemispheres of 20 brains that had been fixed in formalin solution for 40 days. After removal of the arachnoid membrane, the hemispheres were frozen, and the Klingler technique was used for dissection under magnification. Stereoscopic 3-dimensional images of the dissection were obtained for illustration. RESULTS: The optic radiations are located deep within the superior and middle temporal gyri, always above the inferior temporal sulcus. The mean distance between the cortical surface and the lateral edge of the optic radiation was 21 mm. Its fibers are divided into 3 bundles after their origin. The mean distance between the anterior tip of the temporal horn and the Meyer loop was 4.5 mm, between the temporal pole and the anterior border of the Meyer loop was 28.4 mm, and between the limen insulae and the Meyer loop was 10.7 mm. The mean distance between the lateral geniculate body and the lateral margin of the central bundle of the optic radiation was 17.4 mm. CONCLUSION: The white matter fiber dissection reveals the tridimensional intrinsic architecture of the brain, and its knowledge regarding the temporal lobe is particularly important for the neurosurgeon, mostly because of the complexity of the optic radiation and related fibers.


1996 ◽  
Vol 75 (6) ◽  
pp. 2441-2450 ◽  
Author(s):  
D. D. Rasmusson

1. Single neurons in the ventroposterior lateral thalamic nucleus were studied in 10 anesthetized raccoons, 4 of which had undergone amputation of the fourth digit 4-5 mo before recording. Neurons with receptive fields on the glabrous skin of a forepaw digit were examined in response to electrical stimulation of the “on-focus” digit that contained the neuron's receptive field and stimulation of an adjacent, “off-focus” digit. 2. In normal raccoons all neurons responded to on-focus stimulation with an excitation at a short latency (mean 13 ms), whereas only 63% of the neurons responded to off-focus digit stimulation. The off-focus responses had a longer latency (mean 27.2 ms) and a higher threshold than the on-focus responses (800 and 452 microA, respectively). Only 3 of 32 neurons tested with off-focus stimulation had both a latency and a threshold within the range of on-focus values. Inhibition following the excitation was seen in the majority of neurons with both types of stimulation. 3. In the raccoons with digit removal, the region of the thalamus that had lost its major peripheral input (the “deafferented” region) was distinguished from the normal third and fifth digit regions on the basis of the sequence of neuronal receptive fields within a penetration and receptive field size as described previously. 4. Almost all of the neurons in the deafferented region (91%) were excited by stimulation of one or both adjacent digits. The average latency for these responses was shorter (15.3 ms) and the threshold was lower than was the case with off-focus stimulation in control animals. These values were not significantly different from the responses to on-focus stimulation in the animals with digit amputation. 5. These results confirm that reorganization of sensory pathways can be observed at the thalamic level. In addition to the changes in the somatotopic map that have been shown previously with the use of mechanical stimuli, the present paper demonstrates an improvement in several quantitative measures of single-unit responses. Many of these changes suggest that this reorganization could be explained by an increased effectiveness of preexisting, weak connections from the off-focus digits; however, the increase in the proportion of neurons responding to stimulation of adjacent digits may indicate that sprouting of new connections also occurs.


1985 ◽  
Vol 53 (6) ◽  
pp. 1387-1400 ◽  
Author(s):  
T. Yokota ◽  
N. Koyama ◽  
N. Matsumoto

Recordings were made from single thalamic units in the urethan-chloralose anesthetized cat. Altogether 2,905 trigeminal single units having a receptive field in the contralateral trigeminal integument were isolated from the somatosensory part of nucleus ventralis posteromedialis, or VPM proper. Each isolated unit was tested for responses to a series of mechanical stimuli. The stimuli included brushing the skin, touch, pressure, noxious pinch, and pinpricks. The majority of VPM proper units responded with the greatest discharge frequency to gentle mechanical stimulation: either hair movement or light pressure to the trigeminal integument, but 341 units were identified as trigeminal nociceptive units. They were partitioned into two functionally defined subclasses, nociceptive specific (NS) and wide dynamic range (WDR) units, but not intermingled with low-threshold mechanoreceptive (LTM) units. Both NS and WDR units were found at or near the margin of the VPM proper but not outside this nucleus. This marginal area was referred to as the shell region of the VPM proper. A total of 248 NS units was found within the shell region of the caudal third of the VPM proper. This part was called the NS zone. These units were somatotopically organized. In the rostral part of the NS zone, ophthalmic NS units having a receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary NS units occurred dorsomedially, and mandibular NS units were found ventromedially. In the caudal part of the NS zone, maxillary NS units were encountered in the dorsal shell region, whereas mandibular NS units were found in the ventromedial shell region. Ophthalmic NS units were not found in this part of the NS zone. Altogether 93 WDR units were encountered in the shell region of the VPM proper. They were confined to a narrow band approximately 300 micron wide just rostral to the NS zone. These units were somatotopically organized. Ophthalmic WDR units having a low-threshold center of the receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary WDR units were located dorsomedially, and mandibular WDR units were located ventromedially. The majority of maxillary as well as mandibular WDR units were activated by electrical stimulation of the contralateral maxillary and/or mandibular canine tooth pulp afferents. Both NS and WDR zones of the VPM proper extended into the shell region of the nucleus ventralis posterolateralis (VPL).(ABSTRACT TRUNCATED AT 400 WORDS)


1988 ◽  
Vol 60 (2) ◽  
pp. 438-445 ◽  
Author(s):  
H. A. Martin ◽  
A. I. Basbaum ◽  
E. J. Goetzl ◽  
J. D. Levine

1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.


1983 ◽  
Vol 50 (6) ◽  
pp. 1479-1496 ◽  
Author(s):  
D. R. Kenshalo ◽  
O. Isensee

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.


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