Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “nociceptors”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1979

Ascending projections of nociceptor-driven Lamina I neurones in the cat.

Single unit activity has been recorded from nociceptor-driven Lamina I neurones in the lumbar spinal cord of chloralose anaesthetized and gallamine paralysed cats. Ninety-four nociceptor-driven Lamina I neurones were identified by their superficial location in the dorsal horn and their ability to respond only to noxious stimulation of their cutaneous receptive fields. One-third of the Lamina I neurones responded only to noxious mechanical stimulation of the skin (Class 3a) and two-thirds responded to both mechanical and thermal noxious stimulation (Class 3b). Lissauer's tract was stimulated electrically two and three segments rostral to the recording sites. Ninety percent of the neurones tested showed a post-synaptic excitation mediated by fibres conducting at a mean velocity of 5.2 m/s (range 0.9--13.3 m/s). It is concluded that A delta and C afferent fibres running in Lissauer's tract excite nociceptor-driven Lamina I neurones. Ninety-six percent of the neurones tested showed a long period of inhibition (100--200 ms) following stimulation of large afferent fibres in the dorsal column. This inhibition was increased when the intensity of stimulation recruited Lissauer's tract fibres. Fifteen percent of the neurones tested were antidromically activated by Lissauer's tract stimulation from up to 3 segments rostal to their origin. A further 18.5% were antidromically excited by stimulation of deeper tracts. The mean conduction velocity of the axons of these projecting neurones was 8.6 m/s (range 3.8--16.5 m/s) and thus are small myelinated axons. The Class 3b neurones exhibited a significantly lower conduction velocity (7.5 +/- 2.8 (S.D.) m/s) than the Class 3a neurones (10.7 +/- 3.7 (S.D.) m/s). It is concluded that at least two-thirds of the population of nociceptor-driven Lamina I neurones are segmental interneurones.

Afferent Pathways↗
PubMed1979

The spread of sensitization of polymodal nociceptors in the rabbit from nearby injury and by antidromic nerve stimulation.

1. Ninety-three polymodal nociceptor units with unmyelinated axons were isolated from rabbit sural nerves. Twenty-three were used for control data. These showed normal sensitization on repeated heating of their receptive fields, measured here as a drop in mean heat threshold. 2. Small injuries were made 5 (n = 15) or 10 (n = 12) mm outside the receptive fields of some polymodal nociceptors. This resulted in the development of spontaneous firing and lowered thresholds to heating of the receptive field. 3. Local anaesthetic previously injected into the site of injury blocked this spread of heat sensitization. Previous injection of saline had no effect. 4. Antidromic stimulation of the sural nerve, proximal to the recording site, also resulted in heat sensitization of polymodal nociceptors (n = 10). 5. Possible mechanisms for the spread of sensitization of polymodal nociceptors from nearby injury are discussed. Analogies are drawn between these results and those of Lewis (1935--36) on the spread of cutaneous ;yperalgesia around a skin injury in man.

Action Potentials↗
PubMed2025

Mitochondrial activity tunes nociceptor resilience to excitotoxicity.

The capsaicin receptor, TRPV1, mediates the detection of noxious chemical and thermal stimuli by nociceptors, primary sensory neurons of the pain pathway. Overactivation of TRPV1 leads to cellular damage or death through calcium entry and excitotoxicity. We have exploited this phenomenon to conduct a systematic analysis of excitotoxicity through a genome-wide CRISPRi screen, thereby revealing a comprehensive network of regulatory pathways. We show that decreased expression of mitochondrial electron transport chain (ETC) components protects against capsaicin-induced toxicity and other challenges by mitigating both calcium imbalance and the generation of mitochondrial reactive oxygen species via distinct pathways. Moreover, we confirm the regulatory roles of the ETC in sensory neurons through gain-of-function and loss-of-function experiments. Interestingly, TRPV1+ sensory neurons maintain lower expression of ETC components and can better tolerate excitotoxicity and oxidative stress compared with other sensory neuron subtypes, implicating ETC tuning as an intrinsic cellular strategy that protects nociceptors against excitotoxicity.

Mitochondria↗
PubMed1979

The heat sensitization of polymodal nociceptors in the rabbit and its independence of the local blood flow.

1. The firing frequency of polymodal nociceptor units with C-fibre axons was found to increase exponentially with skin temperature as the latter was raised linearly at 1 degree C/sec. Q10 values ranged from 3.6 to 120. 2. Following skin heating to 54--64 degrees C, average firing thresholds fell substantially. This sensitization was accompanied by a 46% increase in interval by interval variability of firing during heat stimulation. 3. Stopping the blood flow to the saphenous area by ligaturing the femoral or saphenous arteries had no significant effect on heat thresholds, on firing patterns during heat stimulation or on variability of firing in sensitized units. There were no changes in continuous, background firing during periods of arterial ligation. 4. It is concluded that if the maintenance of nociceptor heat sensitization depends on the continuous local production of chemical substances, these substances must either be rapidly broken down locally or able to move only slowly into blood vessels.

Action Potentials↗
PubMed1979

Effects of prostaglandins on peripheral nociceptors in acute inflammation.

The effects of different prostaglandins were determined on (a) the hyperalgesia produced by subplantar injections of yeast given into the hind paws of weanling rats, and (b) the reflex vasopressor responses to bradykinin (BK) injected dose-arterially into the spleen of anaesthetised cats and dogs. In the rat prostaglandins (E1 greater than E2 greater than F2 alpha = F2 beta=A2=D2=I2O) injected into the same paw either with the yeast or 25 min later reduced the latency to the onset of hyperalgesia. In the cat and dog prostaglandins (E1 greater than E2 greater than F2 alpha greater than or equal to F2 beta greater than A1=A2=O) potentiated vasopressor responses to BK and reversed the inhibition of BK responses by indomethacin. It is likely that prostaglandins sensitize peripheral nociceptors through a specific prostaglandin receptor.

Acute Disease↗
PubMed2026

Activation of ASIC3 in nociceptors induces itch without overt pain in a novel mouse model of acid-evoked itch.

OBJECTIVE: Acid-sensing ion channel 3 (ASIC3), a proton-gated cation channel predominantly expressed in primary afferent nociceptors, is an acidosis-related pain generator. Previous experiments suggested that ASIC3 is also involved in the generation of itch. However, mechanistic links between ASIC3 and itch, including the expression of ASIC3 in itch-mediating primary sensory neurons, remain unclear. We examined ASIC3 expression in these sensory neurons and then investigated whether mild acid stimulation could induce ASIC3-dependent itch without overt pain in mice. METHODS: Immunohistochemical analyses were performed using ASIC3-FLAG-enhanced green fluorescent protein-FLAG (FEF) expressing mice. Citric acid was applied with a brush to shaved skin of the nape of the neck or cheek in wild-type and ASIC3 knockout (ASIC3 -/- ) mice. Hindlimb scratching and, in the cheek model, forelimb facial wiping were recorded. RESULTS: ASIC3-expressing neurons and plexin C1-positive/tachykinin 1-negative itch-mediating neurons essentially belonged to distinct subpopulations in dorsal root and trigeminal ganglia. Application of 0.2 M citric acid to the nape induced hindlimb scratching directed toward the citric acid-applied area in wild-type mice, and this response was significantly attenuated in ASIC3 -/- mice. Application of 0.5 M citric acid to the cheek induced ASIC3-dependent itch behavior (hindlimb scratching), accompanied by minimal or no pain behavior (forelimb wiping). CONCLUSION: Given the absence of ASIC3 in typical itch-mediating primary sensory neurons, citric acid-induced ASIC3 activation in nociceptive skin afferents primarily involved in pain likely underlies the observed itch behavior. As 0.5 M citric acid likely represents a weak noxious stimulus, weak activation of these pain-mediating afferents can evoke itch, supporting the intensity theory of itch.

Animals↗
PubMed1978

[Extravagal respiratory reflex from pulmonary nociceptors].

A restricted damage of the lung parenchyma before vagotomy evokes an increase of inspiratory discharges of the diaphragm and an increase of the rate of respiration. Similar damage in vagotomized animals evokes only an increase of inspiratory discharges. The rate of respiration does not alter at all or changes insignificantly. An increase of the depth of respiration evoked by the lung nociceptors innervated by the extravagal afferents is of great importance because the lung ventilation is best provided by deep respiration. Probably not only the afferent fibers of the vagus nerves, but also the extravagal lung afferents must be taken into consideration in analysis of the relationship between the rate and depth of lung ventilation, particularly under pathological conditions.

Animals↗
PubMed1979

Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn.

Functional characteristics of spinal neurons located in the marginal zone (lamina I) and substantia gelatinosa (lamina II) were compared to their structural features by intrcellularly staining the source of unitary potentials with horseradish peroxidase (HRP) in unanesthetized, spinal cats. The responses of postsynaptic units to graded electrical volleys in intact dorsal roots and to physiological stimulation revealed that the peripheral excitatory input to neurons of the region is dominated by slowly conducting afferent fibers; often, the input to a given element is largely from a particular class of receptors. One type commonly seen received its principal peripheral excitation from low threshold mechanoreceptors with A delta or C afferent fibers. Mechanoreceptive elements often exhibited a marked, prolonged habituation and many were not excited by afferent volleys. Other units were predominantly excited by nociceptors with myelinated or unmyelinated fibers, or by thermoreceptors with unmyelinated fibers. A few units (principally the thermoreceptive) showed substantial ongoing activity which was modulated by sensory stimulation, but most had little or none. The HRP staining revealed neuronal morphology in fine detail. No relationship between neuronal configuration and physiological response was discerned. Soma location was not always linked to afferent input, although the cell bodies of nociceptive and thermoreceptive neurons tended to be in lamina I or outer lamina II (SGo) while those of the innocuous mechanoreceptive meurons tended to be in inner lamina II (SGi). The locus of a neuron's major dendritic arborization was more closely related to the source(s) of peripheral excitation. Cells excited by nociceptors with myelinated fibers had major dendritic projections in the marginal zone. Cells excited by nociceptors or thermoreceptors with unmyelinated fibers had important dendritic branching in the SGo. Innocuous mechanoreceptive neurons had primary dendritic arborization in the SGi when the input derived from unmyelinated fibers, or in the SGi and extending into the outer nucleus proprius (lamina III) when the afferent drive came from A delta fibers. These findings support the concept that laminae I and II constitute a major termination region for thin primary afferent fibers, myelinated fibers from nociceptors ending principally in lamina I and unmyelinated fibers from nociceptors, thermoreceptors, and mechanoreceptros terminating predominantly in lamina II. Substantial integrative and distributive functions can be expected of such an afferent termination zone.

Animals↗
PubMed1979

Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers.

Single primary afferent myelinated fibers from cutaneous receptors of cat and monkey were functionally identified by recording from the spinal cord with micropipettes filled with horseradish peroxidase (HRP). Relatively slowly conducting fibers (less than 40 m/sec) from high threshold mechanoreceptors (mechanical nociceptors) and two types of low threshold mechanoreceptor (D-hair and field) were selected for staining. Iontophoresis of the HRP and subsequent histochemical reaction stained the axons recorded from and their collaterals, including terminations, for several millimeters. The termination patterns in the two species proved essentially identical. Ipsilaterally, the mechanical nociceptor fibers terminated principally in the dorsal horn's marginal zone and in the ventral parts of the nucleus proprius (lamina V in the cat). Some of these nociceptors also had terminals in the midline just dorsal to the central canal, contralaterally in the marginal zone, and at the base of the opposite nucleus proprius. In contrast, the D-hair primary afferent axons terminated in the dorsal part of the nucleus proprius overlapping into the innermost portion of the substantia gelatinosa. The field receptor fibers terminated predominantly in the middle part of the nucleus proprius. These results suggest that there is a highly specialized central projection of primary afferent endings which is related to sensory function and not to fiber diameter. The marginal zone and most dorsal parts of the substantia gelatinosa receive direct projections from cutaneous nociceptors but do not have direct input from cutaneous receptors transmitting activity initiated by innocuous stimulation.

Animals↗
PubMed1977

Sensory fibres in ventral roots L7 and Si in the cat.

1. Receptive fields were determined for ninety-eight unmyelinated and 132 myelinated axons in the L7 and S1 cat ventral roots.2. Seventy of the ninety-eight unmyelinated axons had their receptive fields in somatic structures, the skin and deep tissues.3. Of the seventy unmyelinated axons with somatic receptive fields, thirty-five were mechanical nociceptors, fifteen were mechanical and thermal nociceptors, eleven were deep nociceptors, six were thermal receptors, and three were low threshold mechanoceptors.4. Twenty-four of the ninety-eight unmyelinated axons had their receptive fields in visceral structures: the intestine, bladder and vagina.5. We confirm the work of others that myelinated fibres attached to peripheral receptive fields can be found in ventral roots and that the receptive fields and functional qualities of these fibres are as one would expect of dorsal root fibres for the same segments.6. A previous study demonstrated that approximately 30% of the axons in the L7 and S1 cat ventral roots are unmyelinated and arise from dorsal root ganglion cells. The present study confirms that these axons are sensory and that the axons are predominantly cutaneous nociceptors and visceral afferents. Thus it is concluded that the L7 and S1 cat ventral roots have a major sensory component.

Animals↗
PubMed1979

A comparison between the discharges of human nociceptive nerve fibres and the subject's ratings of his sensations.

1. Impulses in cutaneous nerve fibres were recorded percutaneously with tungsten micro-electrodes from the superficial radial nerve of adult human subjects. 2. Eight units studied had conduction velocities below 1.5 m/sec, and thus belong to the class of C fibres. On the basis of their responsiveness to mechanical and to thermal stimuli the units were classified as 'polymodal nociceptors'. 3. Units were tested with 12 sec heat pulses starting from a base line temperature of 43.0-43.5 degrees C. Heat stimuli reaching three different maximal levels were applied in randomized order, the subjects being blind with respect to stimulus size. Each of the eight units studied was tested with more tha 20 stimuli and with four of them were 80-125 stimulus repetitions. 4. After each stimulus the subjects had to rate his sensations on a six-point rating scale extending from 'just noticeable' to 'very hot, painful'. 5. Discrimination between the three stimulus levels by the integtated spike discharges and by the ratings of the subject was compared using the P(A) measure of the Signal Detection Theory. It was found that both the neurophysiological and the psychophysical measurements provided about equal discrimination. 6. In addition it has been found that spike discharges and ratings share a common variance beyond their common dependence on the stimulus level. Among the factors contributing to this interdependence a 'temporal position effect' was the most significant. 7. In spite of this interdependence between discharge rates and subjective ratings, the latter gave a better estimation of the stimulus size than of the discharge rates of the individual C fibre under study. 8. It was concluded that the polymodal C-nociceptors might be instrumental for the quantitative aspects of heat pain sensation. The hypothesis was derived from the present results that, under the conditions of cour experiments, the loss of information in the course of central processing might be about equal to the gain by the parallel processing in a population of nociceptors excited by a stimulus.

Action Potentials↗
PubMed1978

Integration of sensory input in laminae I, II and III of the cat's spinal cord.

There is a growing body of evidence supporting the concept of pain as a specific sense. There are afferent fibers from the skin that respond only to noxious stimuli, the nociceptors. Some nociceptor afferents have small myelinated axons (Adelta) while the rest have unmyelinated axons (C). Among the neurons in the superficial layers of the spinal cord (laminae I, II and III) in the cat is a population that responds exclusively to noxious cutaneous stimuli. This input arrives over the nociceptor afferents. Another population responds best to mild temperature changes, reflecting an input from the thermoreceptive afferents. Many units in these two populations of spinal neurons have been shown to project to the brainstem. Therefore, they comprise a relay to the brain for nociceptive and thermal information. Another population of superficial neurons in the spinal cord responds to gentle mechanical stimuli, particularly to slow movement. They reflect an input from the C mechanoreceptor. This population is characterized by spatal and modality convergence. They do not project to the brain and their functional role is still unknown.

Afferent Pathways↗