Characterization of Cutaneous Primary Afferent Fibers Excited by Acetic Acid in a Model of Nociception in Frogs

2003 ◽  
Vol 90 (2) ◽  
pp. 566-577 ◽  
Author(s):  
Darryl T. Hamamoto ◽  
Donald A. Simone
Keyword(s):  
Acetic Acid ◽  
Hind Limb ◽  
Receptive Fields ◽  
Primary Afferent ◽  
Exposed Skin ◽  
C Fibers ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Low Threshold ◽  
Aβ Fibers

Acetic acid applied to the hind limb of a frog evokes nocifensive behaviors, including a vigorous wiping of the exposed skin, referred to as the wiping response. The aim of this study was to examine the responses of cutaneous primary afferent fibers in frogs to acetic acid (pH 2.84–1.42) applied topically to the skin. Conventional electrophysiological methods were used to record neuronal activity from single identified primary afferent fibers with cutaneous receptive fields on the hind limb. Fibers were classified according to their conduction velocities and responses evoked by mechanical and thermal (heat and cold) stimuli. One hundred and twenty-two mechanosensitive afferent fibers were studied (44 Aβ, 60 Aδ, and 18 C fibers). Thirty-nine percent of all fibers were excited by acetic acid, but a greater percentage of Aδ (52%) and C fibers (44%) were excited than Aβ fibers (20%). Evoked responses of fibers increased with increasingly more acidic pH until the greatest responses were evoked by acetic acid at pH 2.59–2.41. Application of acetic acid at pHs <2.41 evoked less excitation, suggesting that fibers became desensitized. Similar percentages of nociceptors and low-threshold mechanoreceptors were excited by acetic acid. Thus primary afferent fibers were excited by acetic acid at pHs that have been shown to evoke the wiping response in our previous study. The results of the present study suggest that the model of acetic acid-induced nociception in frogs may be useful for studying the mechanisms by which tissue acidosis produces pain.

Response and receptive-field properties of spinomesencephalic tract cells in the cat

1986 ◽  
Vol 55 (1) ◽  
pp. 76-96 ◽  
Author(s):  
R. P. Yezierski ◽  
R. H. Schwartz
Keyword(s):  
Spinal Cord ◽  
Receptive Field ◽  
Dynamic Range ◽  
Receptive Fields ◽  
The Body ◽  
Noxious Stimulation ◽  
Primary Afferent ◽  
Receptive Field Properties ◽  
Afferent Fibers ◽  
Primary Afferent Fibers

Recordings were made from 90 identified spinomesencephalic tract (SMT) cells in the lumbosacral spinal cord of cats anesthetized with alpha-chloralose and pentobarbital sodium. Recording sites were located in laminae I-VIII. Antidromic stimulation sites were located in different regions of the rostral and caudal midbrain including the periaqueductal gray, midbrain reticular formation, and the deep layers of the superior colliculus. Twelve SMT cells were antidromically activated from more than one midbrain level or from sites in the medial thalamus. The mean conduction velocity for the population of cells sampled was 45.2 +/- 21.4 m/s. Cells were categorized based on their responses to graded intensities of mechanical stimuli and the location of excitatory and/or inhibitory receptive fields. Four major categories of cells were encountered: wide dynamic range (WDR); high threshold (HT); deep/tap; and nonresponsive. WDR and HT cells had excitatory and/or inhibitory receptive fields restricted to the ipsilateral hindlimb or extending to other parts of the body including the tail, forelimbs, and face. Some cells had long afterdischarges following noxious stimulation, whereas others had high rates of background activity that was depressed by nonnoxious and noxious stimuli. Deep/tap cells received convergent input from muscle, joint, or visceral primary afferent fibers. The placement of mechanical lesions at different rostrocaudal levels of the cervical spinal cord provided information related to the spinal trajectory of SMT axons. Six axons were located contralateral to the recording electrode in the ventrolateral/medial or lateral funiculi while two were located in the ventrolateral funiculus of the ipsilateral spinal cord. Stimulation at sites used to antidromically activate SMT cells resulted in the inhibition of background and evoked responses for 22 of 25 cells tested. Inhibitory effects were observed on responses evoked by low/high intensity cutaneous stimuli and by the activation of joint or muscle primary afferent fibers. Based on the response and receptive-field properties of SMT cells it is suggested that the SMT may have an important role in somatosensory mechanisms, particularly those related to nociception.

scholarly journals Response Properties of Whisker-Associated Trigeminothalamic Neurons in Rat Nucleus Principalis

2003 ◽  
Vol 89 (1) ◽  
pp. 40-56 ◽  
Author(s):  
Brandon S. Minnery ◽  
Daniel J. Simons
Keyword(s):  
Receptive Fields ◽  
Stimulus Onset ◽  
Response Latencies ◽  
Primary Afferent ◽  
Medial Nucleus ◽  
Afferent Fibers ◽  
Highly Sensitive ◽  
Primary Afferent Fibers ◽  
Stimulus Features ◽  
Nucleus Principalis

Nucleus principalis (PrV) of the brain stem trigeminal complex mediates the processing and transfer of low-threshold mechanoreceptor input en route to the ventroposterior medial nucleus of the thalamus (VPM). In rats, this includes tactile information relayed from the large facial whiskers via primary afferent fibers originating in the trigeminal ganglion (NV). Here we describe the responses of antidromically identified VPM-projecting PrV neurons ( n = 72) to controlled ramp-and-hold deflections of whiskers. For comparison, we also recorded the responses of 64 NV neurons under identical experimental and stimulus conditions. Both PrV and NV neurons responded transiently to stimulus onset (on) and offset (off), and the majority of both populations also displayed sustained, or tonic, responses throughout the plateau phase of the stimulus (75% of NV cells and 93% of PrV cells). Averageon and off response magnitudes were similar between the two populations. In both NV and PrV, cells were highly sensitive to the direction of whisker deflection. Directional tuning was slightly but significantly greater in NV, suggesting that PrV neurons integrate inputs from NV cells differing in their preferred directions. Receptive fields of PrV neurons were typically dominated by a “principal” whisker (PW), whose evoked responses were on average threefold larger than those elicited by any given adjacent whisker (AW; n = 197). However, of the 65 PrV cells for which data from at least two AWs were obtained, most (89%) displayed statistically significanton responses to deflections of one or more AWs. AW response latencies were 2.7 ± 3.8 (SD) ms longer than those of their corresponding PWs, with an inner quartile latency difference of 1–4 ms (±25% of median). The range in latency differences suggests that some adjacent whisker responses arise within PrV itself, whereas others have a longer, multi-synaptic origin, possibly via the spinal trigeminal nucleus. Overall, our findings reveal that the stimulus features encoded by primary afferent neurons are reflected in the responses of VPM-projecting PrV neurons, and that significant convergence of information from multiple whiskers occurs at the first synaptic station in the whisker-to-barrel pathway.

scholarly journals Involvement of Peripheral Purinoceptors in Sympathetic Modulation of Capsaicin-Induced Sensitization of Primary Afferent Fibers

2006 ◽  
Vol 96 (5) ◽  
pp. 2207-2216 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Receptor Agonist ◽  
P2x Receptors ◽  
Intradermal Injection ◽  
Disulfonic Acid ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers

Purinoceptors are distributed in primary afferent terminals, where transmission of nociceptive information is modulated by these receptors. In the present study, we evaluated whether the activation or blockade of purinoceptors of subtypes P2X and P2Y in the periphery affected the sensitization of primary afferents induced by intradermal injection of capsaicin (CAP) and examined their role in sympathetic modulation of sensitization of primary nociceptive afferents. Afferent activity was recorded from single Aδ- and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with α,β-methylene adenosine 5′-triphosphate (α,β-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of Aδ- and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both Aδ- and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by α,β-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid could significantly reduce the CAP-induced sensitization of Aδ- and C-fibers. Pretreatment with uridine 5′-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of Aδ- and C-fibers under sympathetically intact or sympathectomized conditions. Our study supports the view that ATP plays a role in modulation of primary afferent nociceptor sensitivity mainly by P2X receptors. Combined with our previous study, our data also provide further evidence that the sensitization of primary afferent nociceptors is subject to sympathetic modulation by activation of P2X as well as α1-adrenergic receptors.

Aδ and C Primary Afferents Convey Dorsal Root Reflexes After Intradermal Injection of Capsaicin in Rats

2000 ◽  
Vol 84 (5) ◽  
pp. 2695-2698 ◽  
Author(s):  
Qing Lin ◽  
Xiaoju Zou ◽  
William D. Willis
Keyword(s):  
Dorsal Root ◽  
Neurogenic Inflammation ◽  
Low Frequency ◽  
Intradermal Injection ◽  
Spontaneous Firing ◽  
C Fibers ◽  
Dorsal Root Reflex ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Aβ Fibers

Antidromic activity was recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4–6 level and tested for responses to acute cutaneous inflammation produced by intradermal injection of capsaicin. This antidromic activity included low-frequency spontaneous firing and dorsal root reflex (DRR) discharges evoked by applying von Frey hairs to the skin of the foot. DRRs could be recorded from both small myelinated (Aδ) and unmyelinated (C) afferent fibers, as well as from large myelinated (Aβ) fibers. After capsaicin was injected intradermally into the plantar skin of the foot, a significant enhancement of DRR activity was seen in Aδ and C fibers but not in Aβ fibers, and this increase lasted for ∼1 h. This study supports the hypothesis that centrally mediated antidromic activity in Aδ and C primary afferent fibers contributes to the development of neurogenic inflammation, presumably by release of inflammatory substances in the periphery.

Responses of trigeminal brain stem neurons and the digastric muscle to tooth-pulp stimulation in awake cats

1993 ◽  
Vol 69 (1) ◽  
pp. 174-186 ◽  
Author(s):  
F. M. Boissonade ◽  
B. Matthews
Keyword(s):  
Brain Stem ◽  
Receptive Fields ◽  
Short Latency ◽  
Tooth Pulp ◽  
Digastric Muscle ◽  
Primary Afferent ◽  
Afferent Fibers ◽  
Long Latency ◽  
Primary Afferent Fibers ◽  
Awake Animal

1. Cats were prepared for chronic recording from neurons in pars oralis and pars interpolaris of the trigeminal spinal nucleus. Electrodes were implanted into canine teeth for electrical stimulation and the digastric muscle for recording electromyograms. 2. Recordings were made from the animals when they were awake and unrestrained as well as when they were lightly anesthetized. Some neurons were studied under both conditions. 3. In an awake animal, single tooth-pulp stimuli of 0.1 ms duration and < or = 1 mA intensity produced no aversive behavior. 4. The response of trigeminal brain stem neurons in the awake animal to such stimuli consisted of short (approximately 3 ms)- and long (approximately 25 ms)-latency discharges whose thresholds suggested that they were both due to inputs from fast conducting primary afferent fibers. 5. Light anesthesia reduced the number of impulses in both components and in most cases completely abolished the long-latency component evoked by low-intensity stimuli. The threshold of the short-latency component was little affected by light anesthesia. It is postulated that the short-latency component is mediated by a monosynaptic input from primary afferent fibers and the long-latency component by a polysynaptic input from these same fibers. 6. All neurons that responded to tooth-pulp stimulation had inputs from other orofacial sites both in the awake and lightly anesthetized states. After light anesthesia, these receptive fields were altered in only 3 out of 15 neurons. 7. The majority of neurons (18 out of 20) were not spontaneously active in the awake animal. Spontaneous activity in the other two was reduced by light anesthesia. 8. The threshold of the digastric reflex evoked by tooth-pulp stimulation was not altered by light anesthesia, but the size of the response was reduced. 9. The effects of changing the level of anesthesia from deep to light (i.e., without and with reflex withdrawal to squeezing a paw) on the responses to tooth-pulp stimulation were also studied. Decreasing the anesthetic depth tended to decrease the thresholds and increase the magnitude of both the short- and long-latency neuronal responses and the short-latency digastric response.

Primary Afferent Fibers That Contribute to Increased Substance P Receptor Internalization in the Spinal Cord After Injury

1999 ◽  
Vol 81 (3) ◽  
pp. 1379-1390 ◽  
Author(s):  
Brian J. Allen ◽  
Jun Li ◽  
Patrick M. Menning ◽  
Scott D. Rogers ◽  
Joseph Ghilardi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Transection ◽  
Primary Afferent ◽  
Lamina I ◽  
C Fibers ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Stimulation Of

Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. Upon noxious stimulation, substance P (SP) is released from primary afferent fibers into the spinal cord where it interacts with the SP receptor (SPR). The SPR is located throughout the dorsal horn and undergoes endocytosis after agonist binding, which provides a spatial image of SPR-containing neurons that undergo agonist interaction. Under normal conditions, SPR internalization occurs only in SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious stimulation. After nerve transection and inflammation, SPR immunoreactivity increases, and both noxious as well as nonnoxious stimulation produces SPR internalization in the superficial and deep dorsal horn. We investigated the primary afferent fibers that contribute to enhanced SPR internalization in the spinal cord after nerve transection and inflammation. Internalization evoked by electrical stimulation of the sciatic nerve was examined in untreated animals, at 14 days after sciatic nerve transection or sham surgery and at 3 days after hindpaw inflammation. Electrical stimulation was delivered at intensities to excite Aβ fibers only, Aβ and Aδ fibers or A and C fibers as determined by the compound action potential recorded from the tibial nerve. Electrical stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min. Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5% increase in SPR and immunoreactivity in lamina I, respectively. Under normal conditions, stimulation of Aδ or C fibers evoked internalization that was confined to the superficial dorsal horn. After transection or inflammation, there was a 20–24% increase in the proportion of SPR+ lamina I neurons that exhibited internalization evoked by stimulation of Aδ fibers. The proportion of lamina I SPR+ neurons that exhibited internalization after stimulation of C-fibers was not altered by transection or inflammation because this was nearly maximal under normal conditions. Moreover, electrical stimulation sufficient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve transection and in 32–36% of SPR+ neurons in lamina III and IV after inflammation. Stimulation of Aβ fibers alone never evoked internalization in the superficial or deep dorsal horn. These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord after nerve transection and inflammation and suggest that recruitment of neurons that possess the SPR contributes to hyperalgesia.

Sympathetic Modulation of Activity in Aδ- and C-Primary Nociceptive Afferents After Intradermal Injection of Capsaicin in Rats

2005 ◽  
Vol 93 (1) ◽  
pp. 365-377 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Adrenergic Receptors ◽  
Intradermal Injection ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers ◽  
Sympathetic Efferents ◽  
Intact Rats

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Aδ- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Aδ- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 μl) injection, but the enhanced responses of both Aδ- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an α1-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Aδ-fibers. In contrast, a blockade of α2-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Aδ- and C-primary afferent fibers to mechanical stimuli and that α1-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.

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