scholarly journals An ultrafast system for signaling mechanical pain in human skin

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw1297 ◽  
Author(s):  
Saad S. Nagi ◽  
Andrew G. Marshall ◽  
Adarsh Makdani ◽  
Ewa Jarocka ◽  
Jaquette Liljencrantz ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Human Skin ◽  
Single Unit ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Loss Of Function ◽  
Conduction Velocities ◽  
Low Threshold ◽  
Healthy Participants ◽  
Stimulation Of

The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.

Effects of dorsal column stimulation on primate spinothalamic tract neurons

1976 ◽  
Vol 39 (3) ◽  
pp. 534-546 ◽  
Author(s):  
R. D. Foreman ◽  
J. E. Beall ◽  
J. D. Coulter ◽  
W. D. Willis
Keyword(s):  
Electrical Stimulation ◽  
Dorsal Column ◽  
High Threshold ◽  
Primary Afferent Depolarization ◽  
Spinothalamic Tract ◽  
Lateral Column ◽  
Pain Transmission ◽  
Low Threshold ◽  
Dorsal Column Stimulation ◽  
Stimulation Of

The effect of dorsal column stimulation on spinothalamic tract cells was investigated in anesthetized monkeys. The dorsal column stimuli were applied at midthoracic or at cervical levels of the cord, while the responses of spinothalamic tract cells of the lumbosacral enlargement were examined. A dorsal column volley depressed the activity of spinothalamic tract cells for about 150 ms. A similar depression was observed whether the spinothalamic tract cell was classified as hair activated, low, or high threshold, based on its response properties to cutaneous stimulation. The hair-activated and low-threshold spinothalamic tract cells were initially excited by the dorsal column volley, but often it was possible to demonstrate that a depression could be produced by stimuli which were too weak to cause excitation of these cells. Depression was produced both of the responses of spinothalamic tract cells to electrical stimulation of peripheral nerves and to mechanical stimulation of cutaneous nociceptors. A similar depression was produced by electrical stimulation of large afferents in peripheral nerves.The pathway mediating the depression of spinothalamic tract cells was shown to involve antidromic invasion of collaterals of dorsal column fibers. The best points for stimulation of the cord to produce a depression were over the ipsilateral dorsal column. A lesion interrupting the dorsal column eliminated the depression of cells below the lesion, whereas a lesion of much of the lateral column had no effect.The mechanism of the depression is likely to be complex. Apart from interactions at an interneuronal level, dorsal column volleys can be presumed to collide with sensory input from afferents which project up the dorsal column; collision would interfere chiefly with the responses of hair-activated and low-threshold spinothalamic tract cells. In addition, dorsal column volleys were shown to evoke inhibitory postsynaptic potentials in some spinothalamic tract neurons, and they also produced primary afferent depolarization, at least of large cutaneous afferemts.The excitation of hair-activated and low-threshold spinothalamic tract cells argues against their participation in signaling pain, since dorsal column stimulation in humans does not produce pain at stimulus intensities and frequencies which should activate such neurons. Alternatively, an ascending volley in the dorsal column or in other pathways may interfere with pain transmission in the brain.

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat

1990 ◽  
Vol 64 (6) ◽  
pp. 1791-1800 ◽  
Author(s):  
Y. Sahara ◽  
Y. K. Xie ◽  
G. J. Bennett
Keyword(s):  
Electrical Stimulation ◽  
Afferent Input ◽  
Cutaneous Afferents ◽  
High Threshold ◽  
Excitatory Postsynaptic Potential ◽  
Large Component ◽  
Primary Afferent ◽  
Low Threshold ◽  
Wdr Neurons ◽  
Stimulation Of

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types (“deep-inhibited,” “deep-complex,” and “intermediate”) on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.

Increase of Pain Threshold as a Function of Conditioning Electrical Stimulation: An Experimentlal Study with Application to Electro-acupuncture for Pain Suppresssion

1975 ◽  
Vol 03 (02) ◽  
pp. 133-142 ◽  
Author(s):  
Eddy Holmgren
Keyword(s):  
Electrical Stimulation ◽  
Pain Relief ◽  
Pain Threshold ◽  
Interindividual Variation ◽  
High Threshold ◽  
Conditioning Stimulation ◽  
Low Threshold ◽  
Electrical Conditioning ◽  
Threshold Increase ◽  
Stimulation Of

Previous studies have shown that 2 Hz electrical conditioning stimulation of hands and cheeks increased the tooth pain threshold. In the present study the relation between strength of conditioning stimulation and amplitude of pain threshold increase is elucidated. Intense conditioning stimulation, giving subjective beating sensations and extensive muscles twitches, is required to obtain a substantial pain threshold increase. The results are discussed in relation to intensities used in electro-acupuncture and to interindividual variation of the effect. It is suggested that pain relief is obtained due to an inhibitory feed-back mechanism activated, not via low threshold afferents but via high threshold afferents.

New growth elicited in adult leech mechanosensory neurones by peripheral axon damage

1989 ◽  
Vol 143 (1) ◽  
pp. 419-434
Author(s):  
B. A. Bannatyne ◽  
S. E. Blackshaw ◽  
M. McGregor
Keyword(s):  
Peripheral Nerve ◽  
Input Resistance ◽  
Resting Potential ◽  
High Threshold ◽  
Noxious Stimulation ◽  
Axon Damage ◽  
The Central Nervous System ◽  
Low Threshold ◽  
Peripheral Axon ◽  
Stimulation Of

1. New growth in cutaneous mechanosensory neurones elicited by axotomy or axon crush was studied using intracellular injection of horseradish peroxidase at different times after the lesion, ranging from a few days to over a year. 2. Cutting or crushing major, large-calibre axon branches of mechanosensory neurones elicits sprouting of new processes, either centrally within the ganglion neuropile or at the site of the lesion in the peripheral nerve. In contrast, cutting or crushing fine-calibre axon branches supplying accessory parts of the receptive field does not elicit sprouting of the main arbor or main axon branches. 3. Different modalities of mechanosensory neurone respond differently to lesions of their axons. Cutting the axons of high-threshold units responding to noxious stimulation of the skin elicits sprouting of additional processes from the axon hillock region within the central nervous system (CNS), whereas cutting or crushing the axons of low-threshold cells responding to light touch of the skin elicits sprouting at the site of the lesion only, and not within the CNS. 4. In addition to the new growth directed into the peripheral nerve, damaged nociceptive neurones also form new processes that wrap the somata of particular cells within the ganglion. 5. Sprouted processes of axotomized neurones are retained for long periods after the lesion (up to 425 days). 6. The electrical properties of touch and nociceptive cells were studied between 1 and 60 days after axotomy, by intracellular recording from the centrally located cell bodies. The amplitude, width and maximum dV/dt of the action potential and after-hyperpolarization, as well as the resting potential and input resistance, did not change significantly after axotomy, despite the considerable process sprouting known to occur during this time.

Transcutaneous electrical stimulation and the sensation of prickle

1988 ◽  
Vol 59 (4) ◽  
pp. 1116-1127 ◽  
Author(s):  
R. K. Garnsworthy ◽  
R. L. Gully ◽  
P. Kenins ◽  
R. A. Westerman
Keyword(s):  
Electrical Stimulation ◽  
Single Unit ◽  
Saphenous Nerve ◽  
Transcutaneous Electrical Stimulation ◽  
Unpleasant Sensation ◽  
Atopic Status ◽  
Low Threshold ◽  
Single Unit Recordings ◽  
Screening Device ◽  
Relationship Of

1. A high-voltage low-current transcutaneous electrical stimulating device was constructed and tested for its suitability to evaluate fabric-evoked prickle sensitivity in a population of 162 subjects. The initial sensation experienced by subjects with this device was the unpleasant sensation of prickle. 2. Single-unit recordings from the rabbit saphenous nerve established that at threshold most unmyelinated cutaneous receptors, both C low-threshold mechanoreceptive and polymodal nociceptive, were activated by the device. 3. Threshold measurements showed that there was no relationship of electrical threshold to atopic status, nor to fabric prickle threshold. It was concluded that our device preferentially excites unmyelinated afferents, but is not useful as a screening device for fabric intolerance.

Neuronal Responses in Cat Primary Auditory Cortex to Electrical Cochlear Stimulation: IV. Activation Pattern for Sinusoidal Stimulation

2003 ◽  
Vol 89 (6) ◽  
pp. 3190-3204 ◽  
Author(s):  
Marcia W. Raggio ◽  
Christoph E. Schreiner
Keyword(s):  
Electrical Stimulation ◽  
Auditory Cortex ◽  
Primary Auditory Cortex ◽  
High Threshold ◽  
Threshold Behavior ◽  
Activation Pattern ◽  
Short Term ◽  
Low Threshold ◽  
Response Thresholds

Patterns of threshold distributions for single-cycle sinusoidal electrical stimulation and single pulse electrical stimulation were compared in primary auditory cortex of the adult cat. Furthermore, the effects of auditory deprivation on these distributions were evaluated and compared across three groups of adult cats. Threshold distributions for single and multiple unit responses from the middle cortical layers were obtained on the ectosylvian gyrus in an acutely implanted animal; 2 wk after deafening and implantation (short-term group); and neonatally deafened animals implanted following 2–5 yr of deafness (long-term group). For all three cases, we observed similar patterns of circumscribed regions of low response thresholds in the region of primary auditory cortex (AI). A dorsal and a ventral region of low response thresholds were found separated by a narrow, anterior-posterior strip of elevated thresholds. The ventral low-threshold regions in the short-term group were cochleotopically arranged. By contrast, the dorsal region in the short-term animals and both low-threshold regions in long-term deafened animals maintained only weak cochleotopicity. Analysis of the spatial extent of the low-threshold regions revealed that the activated area for sinusoidal stimulation was smaller and more circumscribed than for pulsatile stimulation for both dorsal and ventral AI. The width of the high-threshold ridge that separated the dorsal and ventral low-threshold regions was greater for sinusoidal stimulation. Sinusoidal and pulsatile threshold behavior differed significantly for electrode configurations with low and high minimum thresholds. Differences in threshold behavior and cortical response distributions between the sinusoidal and pulsatile stimulation suggest that stimulus shape plays a significant role in the activation of cortical activity. Differences in the activation pattern for short-term and long-term deafness reflect deafness-induced reorganizational changes based on factors such as differences in excitatory and inhibitory balance that are affected by the stimulation parameters.

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