Characterization of Aδ- and C-Fibers Innervating the Plantar Rat Hindpaw One Day After an Incision

2002 ◽  
Vol 87 (2) ◽  
pp. 721-731 ◽  
Author(s):  
Esther M. Pogatzki ◽  
G. F. Gebhart ◽  
Timothy J. Brennan
Keyword(s):  
Spontaneous Activity ◽  
Mechanical Response ◽  
Tissue Injury ◽  
Mechanical Stimulus ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Median Response ◽  
Sham Procedure ◽  
C Fibers ◽  
Afferent Fibers

Primary hyperalgesia after tissue injury is suggested to result from sensitization of primary afferent fibers, but sensitization to mechanical stimuli has been difficult to demonstrate. In the companion study, sensitization of mechano-responsive Aδ- and C-fibers did not explain pain behaviors 45 min after an incision in the rat hindpaw. In the present study, we examined mechanical response properties of Aδ- and C-fibers innervating the glabrous skin of the plantar hindpaw in rats 1 day after an incision or sham procedure. In behavioral experiments, median withdrawal thresholds to von Frey filaments were reduced from 522 mN before to 61 mN 2 and 20 h after incision; median withdrawal thresholds after sham procedure were stable (522 mN). Responses to a nonpunctate mechanical stimulus were increased after incision. In neurophysiological experiments in these same rats, 67 single afferent fibers were characterized from the left tibial nerve 1 day after sham procedure ( n = 39) or incision ( n = 28); electrical stimulation was used as the search stimulus to identify a representative population of Aδ- and C-fibers. In the incision group, 11 fibers (39%) had spontaneous activity with frequencies ranging from 0.03 to 39.3 imp/s; none were present in the sham group. The median response threshold of Aδ-fibers was less in the incision (56 mN, n = 13) compared with sham (251 mN, n = 26) group, mainly because the proportion of mechanically insensitive afferents (MIAs) was less (8 vs. 54% after sham procedure). Median C-fiber response thresholds were similar in incised (28 mN, n = 15) and sham rats (56 mN, n = 13). Responsiveness to monofilaments was significantly enhanced in Aδ-fibers 1 day after incision; stimulus response functions of C-fibers after incision and after sham procedure did not differ significantly. Only Aδ-fibers but not C-fibers sensitized to the nonpunctate mechanical stimulus. The size of receptive fields was increased in Aδ- and C-fibers 1 day after incision. The results indicate that sensitization of Aδ- and C-fibers is apparent 1 day after incision. Because sensitization of afferent fibers to mechanical stimuli correlated with behavioral results, sensitization may contribute to the reduced withdrawal threshold after incision. Spontaneous activity in Aδ- and C-fibers may account for nonevoked pain behavior and may also contribute to mechanical hyperalgesia by amplifying responses centrally.

Acute Effect of an Incision on Mechanosensitive Afferents in the Plantar Rat Hindpaw

2002 ◽  
Vol 87 (2) ◽  
pp. 712-720 ◽  
Author(s):  
Minna M. Hämäläinen ◽  
G. F. Gebhart ◽  
Timothy J. Brennan
Keyword(s):  
Receptive Field ◽  
Background Activity ◽  
Response Magnitude ◽  
Field Size ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Receptive Field Size ◽  
C Fibers ◽  
Afferent Fibers ◽  
Aβ Fibers

The purpose of this study was to examine which primary afferent fibers are sensitized to mechanical stimuli after an experimental surgical incision to the glabrous skin of the rat hindpaw. Afferent fibers teased from the L5dorsal root or the tibial nerve were recorded in anesthetized rats. The mechanical response properties of each fiber were characterized before and 45 min after an incision (or sham procedure) within the mechanical receptive field. Sensitization is characterized by an expansion of the mechanical receptive field, an increase in background activity, an increase in response magnitude, or a decrease in response threshold. After incision, the background activity and response properties of Aβ-fibers ( n = 9) to mechanical stimuli were unchanged. Four of 13 mechanosensitive Aδ-fibers exhibited sensitization after the incision; response threshold decreased, response magnitude increased, or receptive field size increased. Background activity of Aδ-fibers was not increased by the incision. Sensitization was observed in 4 of 18 mechanosensitive C-fibers 45 min after the incision. Background activity of C-fibers was not increased by the incision. In a group of mechanically insensitive afferent fibers (MIAs), 3 of 7 Aδ-fibers and 4 of 10 C-fibers sensitized 45 min after incision. Response threshold was decreased in only 2 of 17 MIAs; receptive field size increased in 7 of 17 MIAs. Aβ-fibers did not sensitize after the incision, and only 8 of 31 (26%) mechanosensitive Aδ- and C-fibers gave evidence of sensitization. In a group of MIA Aδ- and C-fibers, a greater percentage of 17 fibers studied (41%) were sensitized after incision. In this model, the principal effect of an incision, when examined 45 min after the insult, is an increase in receptive field size of the afferents, particularly those characterized as MIAs. To the extent that the mechanical hyperalgesia characterized in the same model is initiated in the periphery, it would appear that spatial summation of modestly increased response magnitude is important to the development of hyperalgesia.

H2O2 sensitivity of afferent splanchnic C fiber units in vitro

1996 ◽  
Vol 76 (1) ◽  
pp. 371-380 ◽  
Author(s):  
D. W. Adelson ◽  
J. Y. Wei ◽  
L. Kruger
Keyword(s):  
Receptive Fields ◽  
Splanchnic Nerve ◽  
Mechanical Stimuli ◽  
H2o2 Treatment ◽  
Response Latencies ◽  
C Fibers ◽  
Afferent Fibers ◽  
Unit Impulse ◽  
Species Production

1. Single-unit impulse activity evoked by transient, focal application of hydrogen peroxide (H2O2) to identified visceral receptive fields has been characterized in an in vitro rat splanchnic nerve-mesentery preparation. In addition to H2O2 responsiveness, units were characterized in terms of sensitivity to mechanical stimuli, warming, and bradykinin. 2. Mesenteric receptive fields of single splanchnic afferent C fibers in vitro were located with the use of warm (approximately 45 degrees C saline) or mechanical search stimuli. After delimitation of the warm-sensitive and/or mechanosensitive receptive field, units were tested for responsiveness to transient, focal application of H2O2. Microliter volumes (usually 1 microliter) of H2O2 (88-880 mM) evoked responses in 25 of 42 (60%) units with identified warm-sensitive and/or mechanosensitive receptive fields, and in an additional 10 units for which H2O2 was the only effective stimulus. 3. Tachyphylaxis to repeated H2O2 stimulation was observed with interstimulus intervals <30 min, but did not indicate irreversible inactivation of the terminal, because 1) during this period warm and mechanical stimuli elicited responses equal to or greater than those before H2O2 treatment, and 2) H2O2 sensitivity was restored after units were allowed to recover. 4. Eight units unresponsive to an initial dose of H2O2 responded vigorously to a repeated application at the same site, suggesting a potentiating effect of prior H2O2 exposure. 5. Sixty-two percent (8 of 13) of H2O2-responsive units, but no (0 of 6) H2O2-unresponsive units responded to transient, focal bradykinin (9-90 nM) application. 6. An indirect mode of H2O2-evoked afferent excitation in some units was suggested by several observations, including the prolonged (up to 8 min) duration of the response of some units to transient H2O2 application, and the occasionally long (>2 min) response latencies to focal application of H2O2 to defined receptive fields. 7. Excitation of splanchnic neurons by H2O2 may be relevant to the modulation of reactive oxygen species production by immunocompetent cells, because sensory neuropeptides contained in these afferent fibers are known to influence the respiratory burst of macrophages and neutrophils.

Receptive Properties of Mouse Sensory Neurons Innervating Hairy Skin

1997 ◽  
Vol 78 (4) ◽  
pp. 1841-1850 ◽  
Author(s):  
Martin Koltzenburg ◽  
Cheryl L. Stucky ◽  
Gary R. Lewin
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Hair Follicles ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Stimulus Response ◽  
Myelinated Fibers ◽  
C Fibers ◽  
Hairy Skin ◽  
Afferent Fibers

Koltzenburg, Martin, Cheryl L. Stucky, and Gary R. Lewin. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78: 1841–1850, 1997. Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated ( n = 251) or unmyelinated ( n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Aβ, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Aδ, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47°C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 ± 1.4°C (mean ± SE) and an average discharge of 15.8 ± 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 ± 1.9°C and an average discharge of 22.0 ± 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.

scholarly journals Guarding Pain and Spontaneous Activity of Nociceptors after Skin versus  Skin Plus Deep Tissue Incision

2010 ◽  
Vol 112 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Jun Xu ◽  
Timothy J. Brennan
Keyword(s):  
Spontaneous Activity ◽  
Tissue Injury ◽  
Postoperative Pain Management ◽  
Skin Incision ◽  
Control Procedure ◽  
Deep Tissue ◽  
Pain Behaviors ◽  
Sham Procedure ◽  
Guarding Behavior

Background Guarding pain after rat plantar incision is similar to pain at rest in postoperative patients. Spontaneous activity (SA) in nociceptive pathways quite likely transmits such ongoing pain. This study examined the extent of tissue injury by incision on pain behaviors and nociceptor SA. Methods Rat pain behaviors were measured after a sham procedure, skin incision, or skin plus deep tissue incision. Separate groups of rats underwent in vivo single-fiber recording 1 day after a sham procedure, skin, or skin plus deep tissue incision or 7 days after skin plus deep tissue incision. Results Compared with the control procedure, skin incision induced moderate guarding on the day of incision only, whereas skin plus deep tissue incision caused guarding for 5 days. Mechanical and heat hyperalgesia were similar in both incised groups, except that mechanical hyperalgesia lasted longer after skin plus deep tissue incision. On Postoperative Day 1, skin incision (18.2%) produced a similar prevalence of SA in nociceptors as in controls (13.0%), whereas skin plus deep tissue incision generated a greater prevalence of SA (61.0%); SA rate also tended to be greater (6.1 vs. 10.0 imp/s) after skin plus deep tissue incision. Seven days after skin plus deep tissue incision, the SA prevalence was similar (13.6%) as in controls. Conclusions These data demonstrated that incised deep tissue rather than skin had a central role in the genesis of guarding behavior and nociceptor SA. Understanding the responses of deep tissue to incision and the mechanisms for deep tissue pain will improve postoperative pain management.

Activity-dependent sensory signal processing in mechanically responsive slowly conducting meningeal afferents

2014 ◽  
Vol 112 (12) ◽  
pp. 3077-3085 ◽  
Author(s):  
Michael Uebner ◽  
Richard W. Carr ◽  
Karl Messlinger ◽  
Roberto De Col
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Receptive Fields ◽  
Low Frequency ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Action Potential Firing ◽  
Afferent Fibers ◽  
Custom Made ◽  
Activity Dependent

Activity-dependent processes in slowly conducting afferents have been shown to modulate conduction and receptive properties, but it is not known how the frequency of action potential firing determines the responses of such fibers to mechanical stimulation. We examined the responses of slowly conducting meningeal afferents to mechanical stimuli and the influence of preceding action potential activity. In hemisected rat heads with adhering cranial dura mater, recordings were made from meningeal nerves. Dural receptive fields of mechanically sensitive afferent fibers were stimulated with a custom-made electromechanostimulator. Sinusoidal mechanical stimuli of different stimulus durations and amplitudes were applied to produce either high-frequency (phasic) or low-frequency (tonic) discharges. Most fibers showed slowing of their axonal conduction velocity on electrically evoked activity at ≥2 Hz. In this state, the peak firing frequency of phasic responses to a 250-ms mechanical stimulus was significantly reduced compared with control. In contrast, the frequency of tonic responses induced by mechanical stimuli of >500 ms did not change. In a rare subtype of afferents, which showed conduction velocity speeding during activity, an increase in the phasic responses to mechanical stimuli was observed. Depending on the axonal properties of the afferent fibers, encoding of phasic components of mechanical stimuli is altered according to the immediate firing history. Preceding activity in mechanoreceptors slowing their conduction velocity seems to provide a form of low-pass filtering of action potential discharges predominantly reducing the phasic component. This may improve discrimination between harmless and potentially harmful mechanical stimuli in normal tissue.

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.

scholarly journals Inhibition of anandamide hydrolysis attenuates nociceptor sensitization in a murine model of chemotherapy-induced peripheral neuropathy

2015 ◽  
Vol 113 (5) ◽  
pp. 1501-1510 ◽  
Author(s):  
Megan L. Uhelski ◽  
Iryna A. Khasabova ◽  
Donald A. Simone
Keyword(s):  
Peripheral Neuropathy ◽  
Spontaneous Activity ◽  
Mechanical Response ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Mechanical Stimuli ◽  
Painful Neuropathy ◽  
Platinum Based Chemotherapy ◽  
C Fiber

Painful neuropathy frequently develops as a consequence of commonly used chemotherapy agents for cancer treatment and is often a dose-limiting side effect. Currently available analgesic treatments are often ineffective on pain induced by neurotoxicity. Although peripheral administration of cannabinoids, endocannabinoids, and inhibitors of endocannabinoid hydrolysis has been effective in reducing hyperalgesia in models of peripheral neuropathy, including chemotherapy-induced peripheral neuropathy (CIPN), few studies have examined cannabinoid effects on responses of nociceptors in vivo. In this study we determined whether inhibition of fatty acid amide hydrolase (FAAH), which slows the breakdown of the endocannabinoid anandamide (AEA), reduced sensitization of nociceptors produced by chemotherapy. Over the course of a week of daily treatments, mice treated with the platinum-based chemotherapy agent cisplatin developed robust mechanical allodynia that coincided with sensitization of cutaneous C-fiber nociceptors as indicated by the development of spontaneous activity and increased responses to mechanical stimulation. Administration of the FAAH inhibitor URB597 into the receptive field of sensitized C-fiber nociceptors decreased spontaneous activity, increased mechanical response thresholds, and decreased evoked responses to mechanical stimuli. Cotreatment with CB1 (AM281) or CB2 (AM630) receptor antagonists showed that the effect of URB597 was mediated primarily by CB1 receptors. These changes following URB597 were associated with an increase in the endocannabinoid anandamide in the skin. Our results suggest that enhanced signaling in the peripheral endocannabinoid system could be utilized to reduce nociceptor sensitization and pain associated with CIPN.

scholarly journals Extracranial injections of botulinum neurotoxin type A inhibit intracranial meningeal nociceptors’ responses to stimulation of TRPV1 and TRPA1 channels: Are we getting closer to solving this puzzle?

Cephalalgia ◽  
2016 ◽  
Vol 36 (9) ◽  
pp. 875-886 ◽  
Author(s):  
XiChun Zhang ◽  
Andrew M Strassman ◽  
Victor Novack ◽  
Mitchell F Brin ◽  
Rami Burstein
Keyword(s):  
Chronic Migraine ◽  
Mechanical Response ◽  
Receptive Fields ◽  
Chemical Stimulation ◽  
Response Threshold ◽  
Mustard Oil ◽  
Peripheral Tissues ◽  
C Fibers ◽  
Ability To Act ◽  
Stimulation Of

Background Administration of onabotulinumtoxinA (BoNT-A) to peripheral tissues outside the calvaria reduces the number of days chronic migraine patients experience headache. Because the headache phase of a migraine attack, especially those preceded by aura, is thought to involve activation of meningeal nociceptors by endogenous stimuli such as changes in intracranial pressure (i.e. mechanical) or chemical irritants that appear in the meninges as a result of a yet-to-be-discovered sequence of molecular/cellular events triggered by the aura, we sought to determine whether extracranial injections of BoNT-A alter the chemosensitivity of meningeal nociceptors to stimulation of their intracranial receptive fields. Material and methods Using electrophysiological techniques, we identified 161 C- and 135 Aδ-meningeal nociceptors in rats and determined their mechanical response threshold and responsiveness to chemical stimulation of their dural receptive fields with TRPV1 and TRPA1 agonists seven days after BoNT-A administration to different extracranial sites. Two paradigms were compared: distribution of 5 U BoNT-A to the lambdoid and sagittal sutures alone, and 1.25 U to the sutures and 3.75 U to the temporalis and trapezius muscles. Results Seven days after it was administered to tissues outside the calvaria, BoNT-A inhibited responses of C-type meningeal nociceptors to stimulation of their intracranial dural receptive fields with the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. BoNT-A inhibition of responses to capsaicin was more effective when the entire dose was injected along the suture lines than when it was injected into muscles and sutures. As in our previous study, BoNT-A had no effect on non-noxious mechanosensitivity of C-fibers or on responsiveness of Aδ-fibers to mechanical and chemical stimulation. Discussion This study demonstrates that extracranial administration of BoNT-A suppresses meningeal nociceptors’ responses to stimulation of their intracranial dural receptive fields with capsaicin and mustard oil. The findings suggest that surface expression of TRPV1 and TRPA1 channels in dural nerve endings of meningeal nociceptors is reduced seven days after extracranial administration of BoNT-A. In the context of chronic migraine, reduced sensitivity to molecules that activate meningeal nociceptors through the TRPV1 and TRPA1 channels can be important for BoNT-A’s ability to act as a prophylactic.

Involvement of Dorsal Column Nucleus Neurons in Nociceptive Transmission in Aged Rats

2005 ◽  
Vol 94 (6) ◽  
pp. 4178-4187 ◽  
Author(s):  
Junichi Kitagawa ◽  
Yoshiyuki Tsuboi ◽  
Akiko Ogawa ◽  
Ke Ren ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Mechanical Response ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Mechanical Stimulus ◽  
Dorsal Column ◽  
Response Threshold ◽  
Aged Rats ◽  
Adult Rats ◽  
Antidromic Activation ◽  
Nociceptive Transmission

To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P–like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged: 34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from GN. For WDR neurons, the latency to antidromic activation of the ventral posterior lateral nucleus of the thalamus showed no difference between the aged and adult rats. Sciatic nerve stimulation with C-fiber intensity induced responses of GN with significantly longer latency in aged rats than in adults, whereas there was no difference in the response latency to A-fiber intensity stimulation. Background activity and afterdischarges were significantly higher in the aged rats than those in the adult rats. Responses to noxious mechanical and thermal stimuli were significantly greater in the aged rats during application of graded stimuli. There were no significant differences in responses to nonnoxious mechanical stimulus, mechanical response threshold, and the size of the receptive fields between neurons in the aged and adult rats. The area occupied by SP-LI fibers in the GN and the size of SP-LI dorsal root ganglia neurons were significantly larger in aged rats than in adults. The present findings suggest that the hyperexcitability of GN neurons could be involved in abnormal noxious pain sensations with advancing age.

scholarly journals Responses of cutaneous C-fiber afferents and spinal microglia after hindlimb cast immobilization in rats

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hiroki Ota ◽  
Haruna Takebe ◽  
Kazue Mizumura ◽  
Toru Taguchi
Keyword(s):  
Mechanical Response ◽  
Response Threshold ◽  
Lumbar Spinal Cord ◽  
Cast Immobilization ◽  
C Fibers ◽  
Electrophysiological Recordings ◽  
C Fiber ◽  
Lumbar Spinal ◽  
Limb Immobilization

AbstractPrevious studies have shown that persistent limb immobilization using a cast increases nociceptive behavior to somatic stimuli in rats. However, the peripheral neural mechanisms of nociception remain unclear. Using single-fiber electrophysiological recordings in vitro, we examined the general characteristics of cutaneous C-fiber afferents in the saphenous nerve and their responsiveness to mechanical and heat stimuli in a rat model of immobilization-induced pain by subjecting the rats to hindlimb cast immobilization for 4 weeks. The mechanical response of C-fibers appeared to increase in the model; however, statistical analysis revealed that neither the response threshold nor the response magnitude was altered. The general characteristics and heat responses of the C-fibers were not altered. The number of microglia and cell diameters significantly increased in the superficial dorsal horn of the lumbar spinal cord. Thus, activated microglia-mediated spinal mechanisms are associated with the induction of nociceptive hypersensitivity in rats after persistent cast immobilization.

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